Rheumatoid Arthritis
Conditions
Brief summary
This multicenter, open-label study will evaluate the efficacy and safety of subcutaneously administered RoActemra/Actemra (tocilizumab) as monotherapy or in combination with methotrexate or other non-biologic DMARDs in patients with active rheumatoid arthritis and an inadequate response to non-biologic DMARDs or to one anti-TNF. In Phase 1, all patients will receive RoActemra/Actemra 162 mg subcutaneously (sc) weekly for Weeks 1 to 24, with or without methotrexate or other non-biologic DMARDs. For Part 2, patients who achieve sustained clinical DAS28-ESR remission at Weeks 20 and 24 will be randomized to receive RoActemra/Actemra 162 mg sc either weekly or every 2 weeks for Weeks 24 to 48, with or without methotrexate or other non-biologic DMARDs. Patients who do not achieve sustained clinical remission but achieve low disease activity (DAS-ESR \</= 3.2) will continue the initial treatment of RoActemra/Actemra 162 mg sc weekly for Weeks 24 to 48, with or without methotrexate or other non-biologic DMARDs.
Interventions
DRUGDMARD
non-biological disease-modifying antirheumatic drugs at stable dose
DRUGmethotrexate
stable dose
DRUGtocilizumab [RoActemra/Actemra]
162 mg subcutaneously (SC) qw, Weeks 1-24
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/= 18 years of age * Active rheumatoid arthritis (DAS28-ESR \> 3.2), according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria of \> 6 months duration * Patients with intolerance or inadequate response to methotrexate or other non-biologic DMRADs or inadequate response to a first ant-TNF agent * Oral corticosteroids (\</= 10 mg/day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to the maximum recommended dose) are permitted if on a stable dose regimen for \>/= 4 weeks prior to baseline * Permitted non-biologic DMRAD is allowed if at stable dose for at least 4 weeks prior to baseline * Females of childbearing potential and males with female partners of childbearing potential must be using a reliable means of contraception as defined by protocol during the study and for at least 3 months following the last dose of RoActemra/Actemra * Patients with intolerance or inadequate response to methotrexate or other non-biologic DMARDs or inadequate response to first anti-TNF agent
Exclusion criteria
* Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline * Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA; secondary Sjögren's syndrome with RA is permitted * Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis * Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16 * Prior history of current inflammatory joint disease other than RA * Exposure to tocilizumab (either intravenous \[IV\] or SC) at any time prior to baseline * Treatment with any investigational agent with four weeks (or five-half lives of the investigational drug, whichever is longer) of screening * Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline * Previous treatment with Abatacept * History of severe allergic of anaphylactic reactions to human, humanized, or murine monoclonal antibodies * Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal (GI) disease * History of diverticulitis, diverticulitis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose to perforation * Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis \[TB\] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections or nail beds) * Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening * Active TB requiring treatment within the previous 3 years * Positive hepatitis B or hepatitis C * Primary or secondary immunodeficiency (history of or currently active) * Evidence of active malignant disease, malignancies diagnosed with the previous 10 years (including hematological malignancies and solid tumors, except basal of squamous cell carcinoma of the skin diagnosed within the previous 20 years * Pregnant and lactating women * History of alcohol, drug, or chemical abuse within 1 year prior to screening * Neuropathies or other conditions that might interfere with pain evaluation * Inadequate hematological, real of liver function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Clinical Remission, Disease Activity Scale 28 - Erythrocyte Sedimentation Rate <26 (DAS28-ESR <2.6) at Week 20 and Week 24 | Week 20 and Week 24 | The DAS 28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP) and general health status. For this study ESR was used to calculate the DAS 28 score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48 | From week 28 up to week 48 | The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR will be used to calculate the DAS28 score. |
| Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48 | From week 28 up to week 48 | The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR will be used to calculate the DAS28 score. |
| Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | From week 2 until week 24 | The definition of improvement of ACR core set of outcome measures includes an improvement equal or higher to the 20%, 50%, 70%, 90% compared to Baseline in both Swollen Joint Count (SJC) and Tender Joint Count (TJC) as well as in three out of five additional parameters: Physician's Global Assessment of disease activity VAS, patient's Global Assessment of disease activity VAS, patient's assessment of pain VAS, HAQ-DI, and acute phase reactant (either CRP or erythrocyte sedimentation rate \[ESR\]). |
| Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | From week 28 until week 48 | The definition of improvement of ACR core set of outcome measures includes an improvement equal or higher to the 20%, 50%, 70%, 90% compared to Baseline in both Swollen Joint Count (SJC) and Tender Joint Count (TJC) as well as in three out of five additional parameters: Physician's Global Assessment of disease activity VAS, patient's Global Assessment of disease activity VAS, patient's assessment of pain VAS, HAQ-DI, and acute phase reactant (either CRP or erythrocyte sedimentation rate \[ESR\]). |
| Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | From week 2 until week 24 | DAS28-based EULAR response criteria were used to measure individual response as good or moderate depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 ≤5.1. |
| Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | From week 28 until week 48 | DAS28-based EULAR response criteria were used to measure individual response as good or moderate depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 ≤5.1. |
| Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | From baseline to Week 24 | Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter \[cm\] Visual Analog Scale \[VAS\] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement. |
| Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | From week 24 until week 48 | Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter \[cm\] Visual Analog Scale \[VAS\] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement. |
| Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | From baseline to Week 24 | Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity. |
| Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | From week 24 until week 48 | Simplified Disease Activity Index (SDAI) which is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity. |
| Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | From baseline to Week 24 | TCJ is a clinical assessment of 68 joints which are classified as tender/not tender by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints are not be taken into consideration. |
| Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | From week 24 until week 48 | TCJ is a clinical assessment of 68 joints which are classified as tender/not tender by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints are not be taken into consideration. |
| Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | From baseline to Week 24 | SJC is a clinical assessment of 66 joints classified as swollen/not swollen by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints will not be taken into consideration for swelling. |
| Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | From week 24 until week 48 | SJC is a clinical assessment of 66 joints classified as swollen/not swollen by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints will not be taken into consideration for swelling. |
| Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 48 | The DAS 28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP) and general health status. For this study ESR was used to calculate the DAS 28 score. |
| Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | From baseline to Week 24 | Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter \[cm\] Visual Analog Scale \[VAS\] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement. |
| Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | From week 28 until week 48 | Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter \[cm\] Visual Analog Scale \[VAS\] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement. |
| Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | From baseline to Week 24 | Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity. |
| Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | From week 28 until week 48 | Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity. |
| Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | From baseline to Week 24 | The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR is used to calculate the DAS28 score. |
| Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | From week 28 until week 48 | The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR was used to calculate the DAS28 score. |
| Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | From baseline to Week 24 | Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter \[cm\] Visual Analog Scale \[VAS\] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement. |
| Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | From week 28 until week 48 | Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter \[cm\] Visual Analog Scale \[VAS\] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement. |
| Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | From baseline to Week 24 | Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity. |
| Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | From week 28 until week 48 | Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity. |
| Safety: Number of Patients Reporting Adverse Events up to Week 24 | From baseline to Week 24 | Number of patients reporting any treatment emergent adverse event (TEAE), at least one TEAE of special interest, at least one serious TEAE, at least one TEAE leading to dose modification, at least one TEAE leading to discontinuation up to week 24 |
| Safety: Number of Patients Reporting Adverse Events up to Week 48 | From week 24 until week 48 | Number of patients reporting any treatment emergent adverse event (TEAE), at least one TEAE of special interest, at least one serious TEAE, at least one TEAE leading to dose modification, at least one TEAE leading to discontinuation up to week 48 |
| Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24 | From baseline to Week 24 | Number of patients resulting positive to anti-tocilizumab antibodies test are reported. |
| Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | From week 24 until week 48 | Number of patients resulting positive to anti-tocilizumab antibodies test are reported. |
| Immunogenicity: TCZ Levels up to Week 24 | From baseline to Week 24 | Mean concentrations of TCZ in patients' blood are reported. |
| Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit | week 36 and early withdrawal visit | Mean concentrations of TCZ in patients' blood are reported. |
| Immunogenicity: SIL-6R Levels up to Week 24 | From baseline to Week 24 | Mean concentration of SIL-6R in patients' blood are reported. |
| Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Baseline, Week 36 and Early Withdrawal Visit | Mean concentration of SIL-6R in patients' blood are reported. |
| Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | From baseline to Week 24 | This patient reported outcome assessment represents the patient's overall assessment of their current disease activity on a 100 mm horizontal VAS. The extreme left end of the line should be described as no disease activity (symptom-free and no arthritis symptoms) and the extreme right end as maximum disease activity (maximum arthritis disease activity). The line was marked by the participant and the distance from the left edge was recorded and the mean values are reported. |
| Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Baseline, from week 28 until week 48 | This patient reported outcome assessment represents the patient's overall assessment of their current disease activity on a 100 mm horizontal VAS. The extreme left end of the line should be described as no disease activity (symptom-free and no arthritis symptoms) and the extreme right end as maximum disease activity (maximum arthritis disease activity). The line was marked by the participant and the distance from the left edge was recorded and the mean values are reported. |
| Assessment of Pain Reported by the Patient (VAS) Until Week 24 | From baseline to Week 24 | This patient reported outcome assessment represents the patient's assessment of his/her current level of pain on a 100 mm horizontal VAS. The extreme left end of the line should be described as no pain and the extreme right end as unbearable pain. |
| Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | From week 24 up to week 48 | The DAS 28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP) and general health status. For this study ESR was used to calculate the DAS 28 score. |
| Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | From baseline to Week 24 | The Stanford HAQ-DI is a patient-oriented outcome assessment questionnaire specific for RA. It consists of 20 questions referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. |
| Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Baseline, from week 28 until week 48 | The Stanford HAQ-DI is a patient-oriented outcome assessment questionnaire specific for RA. It consists of 20 questions referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. |
| Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | From baseline to Week 24 | The symptom-specific measure FACIT-F assesses chronic illness therapy with special emphasis on fatigue in the past 7 days and consists of 5 dimensions: 1) physical well- being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, and 5) additional concerns. Each of the questions is categorically answered using the scales 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much for a total possible FACIT-F score of 0 to 160. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions. |
| Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Baseline, from week 28 until week 48 | The symptom-specific measure FACIT-F assesses chronic illness therapy with special emphasis on fatigue in the past 7 days and consists of 5 dimensions: 1) physical well- being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, and 5) additional concerns. Each of the questions is categorically answered using the scales 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much for a total possible FACIT-F score of 0 to 160. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions. |
| Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Baseline, from week 28 until week 48 | This patient reported outcome assessment represents the patient's assessment of his/her current level of pain on a 100 mm horizontal VAS. The extreme left end of the line should be described as no pain and the extreme right end as unbearable pain. |
Countries
Ireland, Portugal, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: Tocilizumab Monotherapy Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks. | 74 |
| Phase 1: Combination Therapy Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks. | 327 |
| Total | 401 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| From Baseline Until Week 24 | Adverse Event | 4 | 15 | 0 | 0 | 0 | 0 | 0 |
| From Baseline Until Week 24 | Anaphylaxis or hypersensitivity reaction | 0 | 3 | 0 | 0 | 0 | 0 | 0 |
| From Baseline Until Week 24 | Death | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| From Baseline Until Week 24 | Lack of Efficacy | 2 | 5 | 0 | 0 | 0 | 0 | 0 |
| From Baseline Until Week 24 | Lost to Follow-up | 2 | 3 | 0 | 0 | 0 | 0 | 0 |
| From Baseline Until Week 24 | Physician Decision | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| From Baseline Until Week 24 | Protocol Violation | 0 | 9 | 0 | 0 | 0 | 0 | 0 |
| From Baseline Until Week 24 | Withdrawal by Subject | 2 | 8 | 0 | 0 | 0 | 0 | 0 |
| From Week 24 Until Week 48 | Adverse Event | 0 | 0 | 2 | 1 | 1 | 3 | 1 |
| From Week 24 Until Week 48 | Death | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| From Week 24 Until Week 48 | Lack of Efficacy | 0 | 0 | 1 | 0 | 0 | 2 | 1 |
| From Week 24 Until Week 48 | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| From Week 24 Until Week 48 | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| From Week 24 Until Week 48 | Protocol Violation | 0 | 0 | 1 | 0 | 2 | 0 | 0 |
| From Week 24 Until Week 48 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Phase 1: Tocilizumab Monotherapy | Phase 1: Combination Therapy | Total |
|---|---|---|---|
| Age, Continuous | 53.5 years STANDARD_DEVIATION 12.7 | 53.6 years STANDARD_DEVIATION 12.2 | 53.6 years STANDARD_DEVIATION 12.3 |
| Sex: Female, Male Female | 62 Participants | 264 Participants | 326 Participants |
| Sex: Female, Male Male | 12 Participants | 63 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 74 | 1 / 327 | 0 / 89 | 0 / 90 | 0 / 95 | 2 / 67 | 0 / 2 |
| other Total, other adverse events | 24 / 74 | 119 / 327 | 17 / 89 | 25 / 90 | 30 / 95 | 23 / 67 | 0 / 2 |
| serious Total, serious adverse events | 3 / 74 | 10 / 327 | 2 / 89 | 1 / 90 | 2 / 95 | 5 / 67 | 1 / 2 |
Outcome results
Primary
Percentage of Participants Achieving Sustained Clinical Remission, Disease Activity Scale 28 - Erythrocyte Sedimentation Rate <26 (DAS28-ESR <2.6) at Week 20 and Week 24
The DAS 28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP) and general health status. For this study ESR was used to calculate the DAS 28 score.
Time frame: Week 20 and Week 24
Population: Analyses were conducted on the Full Analysis Set (FAS), i.e. all patients included in the study who received at least one dose of SC TCZ.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentage of Participants Achieving Sustained Clinical Remission, Disease Activity Scale 28 - Erythrocyte Sedimentation Rate <26 (DAS28-ESR <2.6) at Week 20 and Week 24 | 48.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Participants Achieving Sustained Clinical Remission, Disease Activity Scale 28 - Erythrocyte Sedimentation Rate <26 (DAS28-ESR <2.6) at Week 20 and Week 24 | 52.9 Percentage of participants |
p-value: 0.5231Chi-squared
Secondary
Assessment of Pain Reported by the Patient (VAS) Until Week 24
This patient reported outcome assessment represents the patient's assessment of his/her current level of pain on a 100 mm horizontal VAS. The extreme left end of the line should be described as no pain and the extreme right end as unbearable pain.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Week 2 | 53.20 Millimeters | Standard Deviation 24.43 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Week 16 | 32.17 Millimeters | Standard Deviation 22.01 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Week 8 | 35.95 Millimeters | Standard Deviation 24.62 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Week 20 | 26.58 Millimeters | Standard Deviation 22.13 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Week 4 | 43.11 Millimeters | Standard Deviation 24.69 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Week 24 | 23.56 Millimeters | Standard Deviation 21.17 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Week 12 | 29.44 Millimeters | Standard Deviation 22.37 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | LOCF visit | 27.34 Millimeters | Standard Deviation 24.41 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Baseline | 66.38 Millimeters | Standard Deviation 20.7 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | LOCF visit | 29.78 Millimeters | Standard Deviation 25.18 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Baseline | 58.59 Millimeters | Standard Deviation 23.7 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Week 2 | 47.46 Millimeters | Standard Deviation 25.14 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Week 4 | 42.88 Millimeters | Standard Deviation 24.57 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Week 8 | 34.28 Millimeters | Standard Deviation 25.94 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Week 12 | 31.07 Millimeters | Standard Deviation 24.97 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Week 16 | 30.18 Millimeters | Standard Deviation 24 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Week 20 | 28.26 Millimeters | Standard Deviation 24.16 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 24 | Week 24 | 26.43 Millimeters | Standard Deviation 23.3 |
Secondary
Assessment of Pain Reported by the Patient (VAS) Until Week 48
This patient reported outcome assessment represents the patient's assessment of his/her current level of pain on a 100 mm horizontal VAS. The extreme left end of the line should be described as no pain and the extreme right end as unbearable pain.
Time frame: Baseline, from week 28 until week 48
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Baseline | 55.73 Millimeters | Standard Deviation 21.68 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Week 28 | 17.33 Millimeters | Standard Deviation 20.14 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Week 32 | 17.08 Millimeters | Standard Deviation 20.47 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Week 36 | 18.81 Millimeters | Standard Deviation 23.88 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Week 40 | 16.96 Millimeters | Standard Deviation 20.89 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Week 44 | 15.05 Millimeters | Standard Deviation 18.02 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Week 48 | 11.90 Millimeters | Standard Deviation 15.56 |
| Phase 1: Tocilizumab Monotherapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | LOCF visit | 12.74 Millimeters | Standard Deviation 15.99 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | LOCF visit | 16.41 Millimeters | Standard Deviation 19.76 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Baseline | 56.00 Millimeters | Standard Deviation 23.56 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Week 40 | 17.07 Millimeters | Standard Deviation 17.86 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Week 28 | 15.67 Millimeters | Standard Deviation 17.65 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Week 48 | 16.31 Millimeters | Standard Deviation 19.85 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Week 32 | 17.27 Millimeters | Standard Deviation 17.69 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Week 44 | 16.27 Millimeters | Standard Deviation 17.7 |
| Phase 1: Combination Therapy | Assessment of Pain Reported by the Patient (VAS) Until Week 48 | Week 36 | 14.36 Millimeters | Standard Deviation 15.65 |
Secondary
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24
The symptom-specific measure FACIT-F assesses chronic illness therapy with special emphasis on fatigue in the past 7 days and consists of 5 dimensions: 1) physical well- being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, and 5) additional concerns. Each of the questions is categorically answered using the scales 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much for a total possible FACIT-F score of 0 to 160. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Week 2 | 86.64 FACIT-F score | Standard Deviation 25 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Week 16 | 98.41 FACIT-F score | Standard Deviation 27.08 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Week 4 | 92.26 FACIT-F score | Standard Deviation 25.3 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Week 20 | 102.46 FACIT-F score | Standard Deviation 27.24 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Week 8 | 96.45 FACIT-F score | Standard Deviation 25.88 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Week 24 | 104.36 FACIT-F score | Standard Deviation 27.16 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Week 12 | 98.29 FACIT-F score | Standard Deviation 25.47 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | LOCF visit | 101.38 FACIT-F score | Standard Deviation 28.24 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Baseline | 81.72 FACIT-F score | Standard Deviation 24.75 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | LOCF visit | 104.65 FACIT-F score | Standard Deviation 28.07 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Week 4 | 99.54 FACIT-F score | Standard Deviation 27.15 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Week 8 | 103.46 FACIT-F score | Standard Deviation 27.25 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Baseline | 89.16 FACIT-F score | Standard Deviation 24.49 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Week 2 | 95.82 FACIT-F score | Standard Deviation 25.42 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Week 12 | 104.08 FACIT-F score | Standard Deviation 26.79 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Week 16 | 105.51 FACIT-F score | Standard Deviation 26.94 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Week 20 | 104.91 FACIT-F score | Standard Deviation 27.47 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 | Week 24 | 107.01 FACIT-F score | Standard Deviation 27.6 |
Secondary
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48
The symptom-specific measure FACIT-F assesses chronic illness therapy with special emphasis on fatigue in the past 7 days and consists of 5 dimensions: 1) physical well- being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, and 5) additional concerns. Each of the questions is categorically answered using the scales 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much for a total possible FACIT-F score of 0 to 160. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions.
Time frame: Baseline, from week 28 until week 48
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Week 32 | 23.62 FACIT-F score | Standard Deviation 4.16 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Week 40 | 23.39 FACIT-F score | Standard Deviation 4.4 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Week 28 | 23.50 FACIT-F score | Standard Deviation 3.82 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Week 44 | 23.48 FACIT-F score | Standard Deviation 4.21 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Week 36 | 23.23 FACIT-F score | Standard Deviation 4.21 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Week 48 | 23.95 FACIT-F score | Standard Deviation 3.79 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | LOCF visit | 23.69 FACIT-F score | Standard Deviation 4.07 |
| Phase 1: Tocilizumab Monotherapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Baseline | 17.36 FACIT-F score | Standard Deviation 5.16 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | LOCF visit | 22.88 FACIT-F score | Standard Deviation 4.85 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Week 48 | 22.87 FACIT-F score | Standard Deviation 4.87 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Baseline | 17.13 FACIT-F score | Standard Deviation 5.67 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Week 28 | 23.12 FACIT-F score | Standard Deviation 4.47 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Week 32 | 22.98 FACIT-F score | Standard Deviation 4.86 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Week 36 | 22.90 FACIT-F score | Standard Deviation 4.64 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Week 40 | 23.02 FACIT-F score | Standard Deviation 4.38 |
| Phase 1: Combination Therapy | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 | Week 44 | 23.13 FACIT-F score | Standard Deviation 4.45 |
Secondary
Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24
The Stanford HAQ-DI is a patient-oriented outcome assessment questionnaire specific for RA. It consists of 20 questions referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Week 4 | 1.20 HAQ-DI score | Standard Deviation 0.74 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Week 16 | 0.99 HAQ-DI score | Standard Deviation 0.72 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Week 2 | 1.39 HAQ-DI score | Standard Deviation 0.74 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Week 20 | 0.88 HAQ-DI score | Standard Deviation 0.7 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Baseline | 1.49 HAQ-DI score | Standard Deviation 0.76 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Week 24 | 0.85 HAQ-DI score | Standard Deviation 0.71 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Week 12 | 0.99 HAQ-DI score | Standard Deviation 0.74 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | LOCF visit | 0.97 HAQ-DI score | Standard Deviation 0.76 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Week 8 | 1.10 HAQ-DI score | Standard Deviation 0.75 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | LOCF visit | 0.88 HAQ-DI score | Standard Deviation 0.73 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Baseline | 1.36 HAQ-DI score | Standard Deviation 0.7 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Week 2 | 1.18 HAQ-DI score | Standard Deviation 0.69 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Week 4 | 1.05 HAQ-DI score | Standard Deviation 0.69 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Week 8 | 0.95 HAQ-DI score | Standard Deviation 0.71 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Week 12 | 0.91 HAQ-DI score | Standard Deviation 0.71 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Week 16 | 0.87 HAQ-DI score | Standard Deviation 0.7 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Week 20 | 0.83 HAQ-DI score | Standard Deviation 0.71 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 | Week 24 | 0.82 HAQ-DI score | Standard Deviation 0.7 |
Secondary
Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48
The Stanford HAQ-DI is a patient-oriented outcome assessment questionnaire specific for RA. It consists of 20 questions referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.
Time frame: Baseline, from week 28 until week 48
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Baseline | 1.21 HAQ-DI score | Standard Deviation 0.68 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Week 28 | 0.58 HAQ-DI score | Standard Deviation 0.56 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Week 32 | 0.55 HAQ-DI score | Standard Deviation 0.58 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Week 36 | 0.60 HAQ-DI score | Standard Deviation 0.6 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Week 40 | 0.55 HAQ-DI score | Standard Deviation 0.56 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Week 44 | 0.53 HAQ-DI score | Standard Deviation 0.57 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Week 48 | 0.53 HAQ-DI score | Standard Deviation 0.61 |
| Phase 1: Tocilizumab Monotherapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | LOCF visit | 0.55 HAQ-DI score | Standard Deviation 0.61 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | LOCF visit | 0.56 HAQ-DI score | Standard Deviation 0.66 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Baseline | 1.20 HAQ-DI score | Standard Deviation 0.7 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Week 40 | 0.61 HAQ-DI score | Standard Deviation 0.67 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Week 28 | 0.57 HAQ-DI score | Standard Deviation 0.64 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Week 48 | 0.57 HAQ-DI score | Standard Deviation 0.66 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Week 32 | 0.57 HAQ-DI score | Standard Deviation 0.63 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Week 44 | 0.58 HAQ-DI score | Standard Deviation 0.66 |
| Phase 1: Combination Therapy | Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 | Week 36 | 0.56 HAQ-DI score | Standard Deviation 0.64 |
Secondary
Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24
Number of patients resulting positive to anti-tocilizumab antibodies test are reported.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24 | Screen - Baseline | 6 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24 | Screen - Week 12 | 1 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24 | Screen - Week 24 | 3 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24 | Confirmatory - Baseline | 4 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24 | Confirmatory - Week 12 | 1 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24 | Confirmatory - Week 24 | 1 Number of participants |
| Phase 1: Combination Therapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24 | Confirmatory - Week 12 | 0 Number of participants |
| Phase 1: Combination Therapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24 | Screen - Baseline | 13 Number of participants |
| Phase 1: Combination Therapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24 | Confirmatory - Baseline | 5 Number of participants |
| Phase 1: Combination Therapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24 | Screen - Week 12 | 2 Number of participants |
| Phase 1: Combination Therapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24 | Confirmatory - Week 24 | 3 Number of participants |
| Phase 1: Combination Therapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24 | Screen - Week 24 | 9 Number of participants |
Secondary
Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48
Number of patients resulting positive to anti-tocilizumab antibodies test are reported.
Time frame: From week 24 until week 48
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Screen - Week 36 | 0 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Screen - Week 48 | 1 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Confirmatory - Week 36 | 0 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Confirmatory - Week 48 | 0 Number of participants |
| Phase 1: Combination Therapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Screen - Week 48 | 3 Number of participants |
| Phase 1: Combination Therapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Confirmatory - Week 36 | 0 Number of participants |
| Phase 1: Combination Therapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Confirmatory - Week 48 | 0 Number of participants |
| Phase 1: Combination Therapy | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Screen - Week 36 | 0 Number of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Confirmatory - Week 36 | 0 Number of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Screen - Week 48 | 2 Number of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Confirmatory - Week 48 | 0 Number of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Screen - Week 36 | 0 Number of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Confirmatory - Week 48 | 1 Number of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Screen - Week 48 | 3 Number of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Screen - Week 36 | 2 Number of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 | Confirmatory - Week 36 | 1 Number of participants |
Secondary
Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit
Mean concentration of SIL-6R in patients' blood are reported.
Time frame: Baseline, Week 36 and Early Withdrawal Visit
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Baseline | 39.87 mcg/ml | Standard Deviation 10.46 |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Early withdrawal visit | 412.53 mcg/ml | Standard Deviation 323.49 |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Week 36 | 539.89 mcg/ml | Standard Deviation 152.71 |
| Phase 1: Combination Therapy | Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Week 36 | 476.28 mcg/ml | Standard Deviation 156.5 |
| Phase 1: Combination Therapy | Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Baseline | 39.70 mcg/ml | Standard Deviation 16.46 |
| Phase 1: Combination Therapy | Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Early withdrawal visit | 643.00 mcg/ml | — |
| Phase 2 Arm A2 - Monotherapy - q2w | Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Week 36 | 542.99 mcg/ml | Standard Deviation 168.3 |
| Phase 2 Arm A2 - Monotherapy - q2w | Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Baseline | 39.39 mcg/ml | Standard Deviation 11.24 |
| Phase 2 Arm A2 - Monotherapy - q2w | Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Early withdrawal visit | 338.38 mcg/ml | Standard Deviation 230.82 |
| Phase 2 Arm A2 - Combination Therapy - q2w | Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Baseline | 43.11 mcg/ml | Standard Deviation 11.85 |
| Phase 2 Arm A2 - Combination Therapy - q2w | Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Early withdrawal visit | 217.74 mcg/ml | Standard Deviation 236.21 |
| Phase 2 Arm A2 - Combination Therapy - q2w | Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Week 36 | 552.65 mcg/ml | Standard Deviation 184.21 |
| Phase 2 Arm D: Non Responders | Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Baseline | 37.30 mcg/ml | Standard Deviation 11.46 |
| Phase 2 Arm D: Non Responders | Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit | Early withdrawal visit | 513.00 mcg/ml | — |
Secondary
Immunogenicity: SIL-6R Levels up to Week 24
Mean concentration of SIL-6R in patients' blood are reported.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: SIL-6R Levels up to Week 24 | Week 24 | 570.49 mcg/ml | Standard Deviation 198.26 |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: SIL-6R Levels up to Week 24 | Baseline | 42.85 mcg/ml | Standard Deviation 16.26 |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: SIL-6R Levels up to Week 24 | Week 12 | 566.47 mcg/ml | Standard Deviation 210.49 |
| Phase 1: Combination Therapy | Immunogenicity: SIL-6R Levels up to Week 24 | Baseline | 39.29 mcg/ml | Standard Deviation 11.1 |
| Phase 1: Combination Therapy | Immunogenicity: SIL-6R Levels up to Week 24 | Week 12 | 570.34 mcg/ml | Standard Deviation 228.54 |
| Phase 1: Combination Therapy | Immunogenicity: SIL-6R Levels up to Week 24 | Week 24 | 565.34 mcg/ml | Standard Deviation 198.32 |
Secondary
Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit
Mean concentrations of TCZ in patients' blood are reported.
Time frame: week 36 and early withdrawal visit
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit | Week 36 | 48.47 mcg/ml | Standard Deviation 30.17 |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit | Early withdrawal visit | 36.45 mcg/ml | Standard Deviation 18.03 |
| Phase 1: Combination Therapy | Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit | Early withdrawal visit | 19.20 mcg/ml | — |
| Phase 1: Combination Therapy | Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit | Week 36 | 16.77 mcg/ml | Standard Deviation 16.1 |
| Phase 2 Arm A2 - Monotherapy - q2w | Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit | Week 36 | 41.89 mcg/ml | Standard Deviation 28.82 |
| Phase 2 Arm A2 - Monotherapy - q2w | Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit | Early withdrawal visit | 24.43 mcg/ml | Standard Deviation 20.83 |
| Phase 2 Arm A2 - Combination Therapy - q2w | Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit | Early withdrawal visit | 13.75 mcg/ml | Standard Deviation 4.6 |
| Phase 2 Arm A2 - Combination Therapy - q2w | Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit | Week 36 | 48.33 mcg/ml | Standard Deviation 25.79 |
| Phase 2 Arm D: Non Responders | Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit | Early withdrawal visit | 1.78 mcg/ml | — |
Secondary
Immunogenicity: TCZ Levels up to Week 24
Mean concentrations of TCZ in patients' blood are reported.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: TCZ Levels up to Week 24 | Baseline | 0.49 mcg/ml | — |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: TCZ Levels up to Week 24 | Week 12 | 37.97 mcg/ml | Standard Deviation 20.11 |
| Phase 1: Tocilizumab Monotherapy | Immunogenicity: TCZ Levels up to Week 24 | Week 24 | 46.42 mcg/ml | Standard Deviation 28.35 |
| Phase 1: Combination Therapy | Immunogenicity: TCZ Levels up to Week 24 | Baseline | 0.67 mcg/ml | Standard Deviation 0.34 |
| Phase 1: Combination Therapy | Immunogenicity: TCZ Levels up to Week 24 | Week 12 | 41.23 mcg/ml | Standard Deviation 20.89 |
| Phase 1: Combination Therapy | Immunogenicity: TCZ Levels up to Week 24 | Week 24 | 46.87 mcg/ml | Standard Deviation 27.65 |
Secondary
Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48
Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter \[cm\] Visual Analog Scale \[VAS\] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
Time frame: From week 24 until week 48
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | LOCF visit | -25.74 CDAI score | Standard Deviation 11.29 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Week 24 | -25.54 CDAI score | Standard Deviation 10.6 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Week 28 | -24.75 CDAI score | Standard Deviation 10.64 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Week 32 | -24.56 CDAI score | Standard Deviation 12.93 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Week 36 | -23.90 CDAI score | Standard Deviation 11.56 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Week 40 | -25.16 CDAI score | Standard Deviation 10.43 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Week 44 | -25.45 CDAI score | Standard Deviation 10.11 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Week 48 | -26.44 CDAI score | Standard Deviation 11.13 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Baseline values | 29.27 CDAI score | Standard Deviation 10.9 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Week 48 | -25.13 CDAI score | Standard Deviation 12.51 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Baseline values | 29.64 CDAI score | Standard Deviation 12.13 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Week 36 | -25.45 CDAI score | Standard Deviation 11.42 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Week 24 | -25.34 CDAI score | Standard Deviation 12.1 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Week 44 | -25.26 CDAI score | Standard Deviation 11.75 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Week 28 | -24.01 CDAI score | Standard Deviation 12.3 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | LOCF visit | -24.87 CDAI score | Standard Deviation 12.67 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Week 40 | -25.45 CDAI score | Standard Deviation 11.75 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 | Week 32 | -25.12 CDAI score | Standard Deviation 11.64 |
Secondary
Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24
TCJ is a clinical assessment of 68 joints which are classified as tender/not tender by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints are not be taken into consideration.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Week 2 | -4.31 TJC | Standard Deviation 7.56 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Week 16 | -13.43 TJC | Standard Deviation 12.35 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Week 8 | -9.81 TJC | Standard Deviation 10.37 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Week 20 | -13.65 TJC | Standard Deviation 11.73 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Week 4 | -7.04 TJC | Standard Deviation 11.77 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Week 24 | -15.47 TJC | Standard Deviation 13.35 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Week 12 | -12.27 TJC | Standard Deviation 10.47 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | LOCF visit | -14.36 TJC | Standard Deviation 12.87 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Baseline visit | 18.05 TJC | Standard Deviation 12.98 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | LOCF visit | -13.19 TJC | Standard Deviation 11.75 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Baseline visit | 19.12 TJC | Standard Deviation 13.38 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Week 2 | -5.00 TJC | Standard Deviation 8.06 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Week 4 | -7.96 TJC | Standard Deviation 9.43 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Week 8 | -10.90 TJC | Standard Deviation 11.1 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Week 12 | -12.01 TJC | Standard Deviation 10.88 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Week 16 | -13.09 TJC | Standard Deviation 11.02 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Week 20 | -13.70 TJC | Standard Deviation 11.48 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 | Week 24 | -14.20 TJC | Standard Deviation 11.46 |
Secondary
Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48
TCJ is a clinical assessment of 68 joints which are classified as tender/not tender by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints are not be taken into consideration.
Time frame: From week 24 until week 48
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | Baseline values | 15.42 TJC | Standard Deviation 9.05 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | Week 28 | -13.66 TJC | Standard Deviation 8.44 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | Week 32 | -13.40 TJC | Standard Deviation 8.99 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | Week 36 | -13.13 TJC | Standard Deviation 8.82 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | Week 40 | -14.06 TJC | Standard Deviation 8.58 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | Week 44 | -14.32 TJC | Standard Deviation 8.25 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | Week 48 | -14.40 TJC | Standard Deviation 8.61 |
| Phase 1: Tocilizumab Monotherapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | LOCF visit | -13.96 TJC | Standard Deviation 8.68 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | LOCF visit | -13.27 TJC | Standard Deviation 12.2 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | Baseline values | 15.97 TJC | Standard Deviation 12.77 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | Week 40 | -14.49 TJC | Standard Deviation 12.07 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | Week 28 | -12.88 TJC | Standard Deviation 11.52 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | Week 48 | -13.43 TJC | Standard Deviation 12.17 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | Week 32 | -13.88 TJC | Standard Deviation 11.43 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | Week 44 | -13.93 TJC | Standard Deviation 11.62 |
| Phase 1: Combination Therapy | Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 | Week 36 | -13.78 TJC | Standard Deviation 11.7 |
Secondary
Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24
Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter \[cm\] Visual Analog Scale \[VAS\] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Week 4 | -13.03 CDAI score | Standard Deviation 10.91 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Week 16 | -23.01 CDAI score | Standard Deviation 12.33 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Week 12 | -21.56 CDAI score | Standard Deviation 11.77 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Week 20 | -24.07 CDAI score | Standard Deviation 11.97 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Week 8 | -18.06 CDAI score | Standard Deviation 11.05 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Week 24 | -25.80 CDAI score | Standard Deviation 13.31 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Baseline values | 33.06 CDAI score | Standard Deviation 12.45 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | LOCF visit | -24.42 CDAI score | Standard Deviation 13.5 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Week 2 | -7.54 CDAI score | Standard Deviation 9.57 |
| Phase 1: Combination Therapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | LOCF visit | -21.58 CDAI score | Standard Deviation 12.85 |
| Phase 1: Combination Therapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Baseline values | 32.06 CDAI score | Standard Deviation 12.28 |
| Phase 1: Combination Therapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Week 2 | -8.62 CDAI score | Standard Deviation 9.22 |
| Phase 1: Combination Therapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Week 4 | -13.23 CDAI score | Standard Deviation 10.65 |
| Phase 1: Combination Therapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Week 8 | -18.46 CDAI score | Standard Deviation 11.61 |
| Phase 1: Combination Therapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Week 12 | -20.60 CDAI score | Standard Deviation 11.42 |
| Phase 1: Combination Therapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Week 16 | -21.79 CDAI score | Standard Deviation 11.57 |
| Phase 1: Combination Therapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Week 20 | -22.88 CDAI score | Standard Deviation 12.1 |
| Phase 1: Combination Therapy | Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 | Week 24 | -23.43 CDAI score | Standard Deviation 11.62 |
Secondary
Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR)
The DAS 28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP) and general health status. For this study ESR was used to calculate the DAS 28 score.
Time frame: From week 24 up to week 48
Population: Analysis was conducted on the FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | Week 32 | -3.97 mm/hr | Standard Deviation 1.38 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | Week 40 | -3.95 mm/hr | Standard Deviation 1.26 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | Week 28 | -3.94 mm/hr | Standard Deviation 1.22 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | Week 44 | -4.05 mm/hr | Standard Deviation 1.17 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | Week 36 | -3.82 mm/hr | Standard Deviation 1.53 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | Week 48 | -4.14 mm/hr | Standard Deviation 1.24 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | Week 24 | -4.07 mm/hr | Standard Deviation 1.03 |
| Phase 1: Combination Therapy | Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | Week 48 | -3.68 mm/hr | Standard Deviation 1.32 |
| Phase 1: Combination Therapy | Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | Week 24 | -4.01 mm/hr | Standard Deviation 1.13 |
| Phase 1: Combination Therapy | Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | Week 28 | -3.78 mm/hr | Standard Deviation 1.31 |
| Phase 1: Combination Therapy | Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | Week 32 | -3.77 mm/hr | Standard Deviation 1.17 |
| Phase 1: Combination Therapy | Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | Week 36 | -3.90 mm/hr | Standard Deviation 1.16 |
| Phase 1: Combination Therapy | Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | Week 40 | -3.84 mm/hr | Standard Deviation 1.19 |
| Phase 1: Combination Therapy | Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) | Week 44 | -3.76 mm/hr | Standard Deviation 1.17 |
Secondary
Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24
Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Week 2 | -20.45 SDAI score | Standard Deviation 19.01 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Week 16 | -37.82 SDAI score | Standard Deviation 31.09 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Week 8 | -32.61 SDAI score | Standard Deviation 26.84 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Week 20 | -36.79 SDAI score | Standard Deviation 25.47 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Week 4 | -27.86 SDAI score | Standard Deviation 23.54 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Week 24 | -41.38 SDAI score | Standard Deviation 31.51 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Week 12 | -36.23 SDAI score | Standard Deviation 27.04 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | LOCF visit | -39.15 SDAI score | Standard Deviation 30.45 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Baseline values | 48.66 SDAI score | Standard Deviation 31.48 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | LOCF visit | -32.73 SDAI score | Standard Deviation 22.84 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Baseline values | 44.40 SDAI score | Standard Deviation 22.91 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Week 2 | -19.50 SDAI score | Standard Deviation 18.75 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Week 4 | -24.34 SDAI score | Standard Deviation 20.98 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Week 8 | -29.34 SDAI score | Standard Deviation 21.96 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Week 12 | -30.95 SDAI score | Standard Deviation 23.58 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Week 16 | -32.66 SDAI score | Standard Deviation 22.79 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Week 20 | -33.95 SDAI score | Standard Deviation 23.05 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 | Week 24 | -34.80 SDAI score | Standard Deviation 22.44 |
Secondary
Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48
Simplified Disease Activity Index (SDAI) which is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity.
Time frame: From week 24 until week 48
Population: Analysis was conducted on the FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Week 36 | -35.29 SDAI score | Standard Deviation 26.55 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Week 40 | -37.26 SDAI score | Standard Deviation 25.48 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Week 28 | -35.15 SDAI score | Standard Deviation 25.9 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Week 44 | -37.09 SDAI score | Standard Deviation 25.17 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Baseline values | 41.45 SDAI score | Standard Deviation 24.9 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Week 48 | -37.93 SDAI score | Standard Deviation 26.32 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Week 32 | -35.60 SDAI score | Standard Deviation 26.97 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | LOCF visit | -36.93 SDAI score | Standard Deviation 25.75 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Week 24 | -37.02 SDAI score | Standard Deviation 24.6 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | LOCF visit | -34.69 SDAI score | Standard Deviation 21.75 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Week 24 | -35.88 SDAI score | Standard Deviation 20.71 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Week 28 | -34.50 SDAI score | Standard Deviation 20.66 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Week 32 | -34.88 SDAI score | Standard Deviation 20.53 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Week 36 | -35.35 SDAI score | Standard Deviation 20.07 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Week 40 | -35.70 SDAI score | Standard Deviation 19.8 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Week 44 | -35.06 SDAI score | Standard Deviation 21.77 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Week 48 | -35.02 SDAI score | Standard Deviation 21.74 |
| Phase 1: Combination Therapy | Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 | Baseline values | 40.92 SDAI score | Standard Deviation 21.42 |
Secondary
Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24
SJC is a clinical assessment of 66 joints classified as swollen/not swollen by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints will not be taken into consideration for swelling.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS.SJC
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Week 8 | -7.38 SJC | Standard Deviation 6.47 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Week 20 | -8.72 SJC | Standard Deviation 7.56 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Baseline values | 10.05 SJC | Standard Deviation 7.99 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Week 2 | -3.22 SJC | Standard Deviation 4.4 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Week 4 | -5.07 SJC | Standard Deviation 5.58 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Week 12 | -7.93 SJC | Standard Deviation 7.13 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Week 16 | -8.35 SJC | Standard Deviation 7.71 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Week 24 | -9.13 SJC | Standard Deviation 7.66 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | LOCF visit | -8.47 SJC | Standard Deviation 7.48 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Week 24 | -8.38 SJC | Standard Deviation 6.59 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Week 8 | -6.81 SJC | Standard Deviation 6.03 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Week 16 | -8.01 SJC | Standard Deviation 6.05 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Week 4 | -5.46 SJC | Standard Deviation 5.41 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Week 20 | -8.37 SJC | Standard Deviation 6.5 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | LOCF visit | -7.71 SJC | Standard Deviation 6.67 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Baseline values | 9.76 SJC | Standard Deviation 6.64 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Week 12 | -7.60 SJC | Standard Deviation 6 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 | Week 2 | -3.42 SJC | Standard Deviation 5.1 |
Secondary
Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48
SJC is a clinical assessment of 66 joints classified as swollen/not swollen by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints will not be taken into consideration for swelling.
Time frame: From week 24 until week 48
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | Baseline values | 9.28 SJC | Standard Deviation 6.52 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | Week 40 | -8.85 SJC | Standard Deviation 6.4 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | Week 32 | -8.54 SJC | Standard Deviation 7.02 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | Week 28 | -8.64 SJC | Standard Deviation 6.19 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | Week 48 | -9.06 SJC | Standard Deviation 6.58 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | Week 36 | -8.48 SJC | Standard Deviation 6.5 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | LOCF visit | -8.82 SJC | Standard Deviation 6.51 |
| Phase 1: Tocilizumab Monotherapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | Week 44 | -8.73 SJC | Standard Deviation 6.62 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | LOCF visit | -8.64 SJC | Standard Deviation 7.33 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | Baseline values | 9.23 SJC | Standard Deviation 7.55 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | Week 28 | -8.14 SJC | Standard Deviation 6.81 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | Week 32 | -8.62 SJC | Standard Deviation 7.13 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | Week 36 | -8.38 SJC | Standard Deviation 6.76 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | Week 40 | -8.51 SJC | Standard Deviation 6.59 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | Week 44 | -8.62 SJC | Standard Deviation 6.97 |
| Phase 1: Combination Therapy | Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 | Week 48 | -8.72 SJC | Standard Deviation 7.34 |
Secondary
Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48
DAS28-based EULAR response criteria were used to measure individual response as good or moderate depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 ≤5.1.
Time frame: From week 28 until week 48
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Good response - week 28 | 82 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Moderate response - week 28 | 5 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Good response - week 32 | 79 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Moderate response - week 32 | 6 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Good response - week 36 | 75 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Moderate response - week 36 | 9 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Good response - week 40 | 75 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Moderate response - week 40 | 9 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Good response - week 44 | 78 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Moderate response - week 44 | 4 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Good response - week 48 | 78 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Moderate response - week 48 | 4 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Good response - LOCF visit | 84 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Moderate response - LOCF visit | 5 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Good response - week 48 | 73 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Good response - week 28 | 77 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Moderate response - week 40 | 7 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Moderate response - week 28 | 10 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Good response - LOCF visit | 74 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Good response - week 32 | 81 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Good response - week 44 | 75 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Moderate response - week 32 | 9 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Moderate response - week 48 | 15 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Good response - week 36 | 80 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Moderate response - week 44 | 13 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Moderate response - week 36 | 8 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Moderate response - LOCF visit | 16 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 | Good response - week 40 | 81 Number of participants |
Secondary
Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24
DAS28-based EULAR response criteria were used to measure individual response as good or moderate depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 ≤5.1.
Time frame: From week 2 until week 24
Population: Analysis was conducted on the FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - week 16 | 45 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - week 2 | 14 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - week 16 | 22 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - week 8 | 37 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - week 20 | 45 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - week 4 | 18 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - week 20 | 18 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - week 8 | 32 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - week 24 | 48 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - week 2 | 36 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - week 24 | 16 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - week 12 | 41 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - LOCF visit | 54 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - week 4 | 49 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - LOCF visit | 19 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - week 12 | 27 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - LOCF visit | 73 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - week 2 | 61 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - week 2 | 196 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - week 4 | 109 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - week 4 | 175 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - week 8 | 162 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - week 8 | 121 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - week 12 | 194 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - week 16 | 209 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - week 16 | 76 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - week 20 | 221 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - week 20 | 56 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - week 24 | 225 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - week 24 | 53 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Good response - LOCF visit | 247 Number of participants |
| Phase 1: Combination Therapy | Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 | Moderate response - week 12 | 95 Number of participants |
Secondary
Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24
This patient reported outcome assessment represents the patient's overall assessment of their current disease activity on a 100 mm horizontal VAS. The extreme left end of the line should be described as no disease activity (symptom-free and no arthritis symptoms) and the extreme right end as maximum disease activity (maximum arthritis disease activity). The line was marked by the participant and the distance from the left edge was recorded and the mean values are reported.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Week 2 | 49.53 Millimeters | Standard Deviation 22.78 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Week 16 | 19.28 Millimeters | Standard Deviation 18.22 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Week 8 | 30.03 Millimeters | Standard Deviation 21.65 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Week 20 | 16.80 Millimeters | Standard Deviation 16.68 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Week 4 | 38.21 Millimeters | Standard Deviation 22.92 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Week 24 | 16.63 Millimeters | Standard Deviation 15.19 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Week 12 | 22.71 Millimeters | Standard Deviation 18.56 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | LOCF visit | 20.36 Millimeters | Standard Deviation 19.25 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Baseline | 65.26 Millimeters | Standard Deviation 19.77 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | LOCF visit | 22.23 Millimeters | Standard Deviation 20.86 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Baseline | 59.40 Millimeters | Standard Deviation 17.61 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Week 2 | 44.16 Millimeters | Standard Deviation 21.97 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Week 4 | 35.19 Millimeters | Standard Deviation 20.83 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Week 8 | 26.04 Millimeters | Standard Deviation 20.59 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Week 12 | 22.24 Millimeters | Standard Deviation 17.97 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Week 16 | 20.71 Millimeters | Standard Deviation 18.65 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Week 20 | 18.79 Millimeters | Standard Deviation 17.79 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 | Week 24 | 19.00 Millimeters | Standard Deviation 18.36 |
Secondary
Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48
This patient reported outcome assessment represents the patient's overall assessment of their current disease activity on a 100 mm horizontal VAS. The extreme left end of the line should be described as no disease activity (symptom-free and no arthritis symptoms) and the extreme right end as maximum disease activity (maximum arthritis disease activity). The line was marked by the participant and the distance from the left edge was recorded and the mean values are reported.
Time frame: Baseline, from week 28 until week 48
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Baseline | 58.97 Millimeters | Standard Deviation 17.4 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Week 28 | 11.97 Millimeters | Standard Deviation 14.1 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Week 32 | 10.78 Millimeters | Standard Deviation 15.33 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Week 36 | 11.99 Millimeters | Standard Deviation 16.23 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Week 40 | 10.62 Millimeters | Standard Deviation 13.49 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Week 44 | 9.50 Millimeters | Standard Deviation 11.3 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Week 48 | 8.13 Millimeters | Standard Deviation 10.52 |
| Phase 1: Tocilizumab Monotherapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | LOCF visit | 8.97 Millimeters | Standard Deviation 11.63 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | LOCF visit | 10.21 Millimeters | Standard Deviation 13.96 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Baseline | 60.96 Millimeters | Standard Deviation 20.13 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Week 40 | 10.94 Millimeters | Standard Deviation 14.12 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Week 28 | 12.74 Millimeters | Standard Deviation 15.07 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Week 48 | 9.99 Millimeters | Standard Deviation 13.88 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Week 32 | 10.80 Millimeters | Standard Deviation 11.36 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Week 44 | 10.06 Millimeters | Standard Deviation 12.14 |
| Phase 1: Combination Therapy | Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 | Week 36 | 10.30 Millimeters | Standard Deviation 13.2 |
Secondary
Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48
The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR will be used to calculate the DAS28 score.
Time frame: From week 28 up to week 48
Population: Analysis was conducted on the FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48 | Week 28 | 88.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48 | Week 32 | 87.2 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48 | Week 36 | 80.2 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48 | Week 40 | 82.1 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48 | Week 44 | 89.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48 | Week 48 | 91.5 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48 | Week 44 | 78.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48 | Week 28 | 84.1 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48 | Week 40 | 80.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48 | Week 32 | 81.1 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48 | Week 48 | 73.9 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48 | Week 36 | 86.4 Percentage of participants |
Secondary
Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48
The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR will be used to calculate the DAS28 score.
Time frame: From week 28 up to week 48
Population: Analysis was conducted on the FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48 | Week 36 | 93.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48 | Week 28 | 96.6 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48 | Week 32 | 96.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48 | Week 40 | 98.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48 | Week 44 | 98.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48 | Week 48 | 100.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48 | Week 44 | 95.5 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48 | Week 40 | 98.9 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48 | Week 28 | 96.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48 | Week 48 | 95.5 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48 | Week 32 | 95.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48 | Week 36 | 97.7 Percentage of participants |
Secondary
Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24
Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | Week 4 | 27.1 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | Week 16 | 63.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | LOCF visit | 63.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | Week 20 | 65.6 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | Week 8 | 41.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | Week 24 | 74.6 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | Week 2 | 16.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | Week 12 | 58.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | LOCF visit | 56.9 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | Week 4 | 28.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | Week 8 | 48.1 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | Week 12 | 55.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | Week 16 | 62.5 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | Week 20 | 66.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | Week 24 | 67.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 | Week 2 | 17.6 Percentage of participants |
Secondary
Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48
Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity.
Time frame: From week 28 until week 48
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | Week 36 | 79.1 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | Week 44 | 91.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | Week 28 | 84.9 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | Week 48 | 93.9 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | Week 40 | 86.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | LOCF Visit | 91.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | Week 32 | 89.5 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | LOCF Visit | 81.1 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | Week 28 | 83.89 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | Week 32 | 85.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | Week 36 | 87.5 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | Week 40 | 86.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | Week 44 | 82.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 | Week 48 | 81.8 Percentage of participants |
Secondary
Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24
Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter \[cm\] Visual Analog Scale \[VAS\] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | Week 2 | 13.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | Week 4 | 24.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | Week 8 | 41.1 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | Week 12 | 57.1 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | Week 16 | 62.3 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | Week 20 | 66.2 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | Week 24 | 71.9 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | LOCF visit | 66.2 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | LOCF visit | 61.2 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | Week 2 | 16.9 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | Week 16 | 60.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | Week 4 | 26.9 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | Week 24 | 66.9 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | Week 8 | 47.5 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | Week 20 | 65.1 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 | Week 12 | 52.4 Percentage of participants |
Secondary
Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48
Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter \[cm\] Visual Analog Scale \[VAS\] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
Time frame: From week 28 until week 48
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | Week 36 | 80.2 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | Week 44 | 89.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | Week 28 | 86.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | Week 48 | 92.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | Week 40 | 86.9 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | LOCF Visit | 91.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | Week 32 | 89.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | LOCF Visit | 87.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | Week 28 | 85.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | Week 32 | 86.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | Week 36 | 89.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | Week 40 | 88.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | Week 44 | 85.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 | Week 48 | 87.6 Percentage of participants |
Secondary
Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24
The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR is used to calculate the DAS28 score.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | Week 24 | 75.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | Week 8 | 50.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | Week 12 | 58.6 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | Week 16 | 66.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | Week 20 | 67.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | Week 4 | 26.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | LOCF visit | 73.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | Week 2 | 21.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | LOCF visit | 74.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | Week 8 | 55.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | Week 16 | 72.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | Week 20 | 78.2 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | Week 2 | 21.5 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | Week 4 | 36.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | Week 12 | 67.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 | Week 24 | 81.1 Percentage of participants |
Secondary
Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48
The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR was used to calculate the DAS28 score.
Time frame: From week 28 until week 48
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | Week 40 | 89.3 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | Week 28 | 95.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | Week 44 | 96.3 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | Week 48 | 95.1 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | Week 36 | 87.2 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | LOCF Visit | 94.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | Week 32 | 91.9 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | LOCF Visit | 85.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | Week 28 | 88.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | Week 32 | 92.2 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | Week 36 | 92.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | Week 40 | 92.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | Week 48 | 86.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 | Week 44 | 87.5 Percentage of participants |
Secondary
Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24
The definition of improvement of ACR core set of outcome measures includes an improvement equal or higher to the 20%, 50%, 70%, 90% compared to Baseline in both Swollen Joint Count (SJC) and Tender Joint Count (TJC) as well as in three out of five additional parameters: Physician's Global Assessment of disease activity VAS, patient's Global Assessment of disease activity VAS, patient's assessment of pain VAS, HAQ-DI, and acute phase reactant (either CRP or erythrocyte sedimentation rate \[ESR\]).
Time frame: From week 2 until week 24
Population: Analysis was conducted on the FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - LOCF visit | 77.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - week 2 | 5.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - week 2 | 9.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - week 4 | 12.3 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - Week 8 | 67.1 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - week 8 | 17.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - week 4 | 20.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - week 12 | 32.9 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - Week 20 | 73.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - week 16 | 29.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - week 8 | 37.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - week 20 | 33.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - Week 12 | 80.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - week 24 | 40.6 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - week 12 | 51.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - LOCF visit | 37.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - Week 2 | 27.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - week 2 | 1.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - week 16 | 53.6 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - week 4 | 2.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - Week 16 | 79.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - week 8 | 6.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - week 20 | 58.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - week 12 | 12.9 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - Week 24 | 79.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - week 16 | 13.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - week 20 | 13.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - week 24 | 59.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - week 24 | 23.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - Week 4 | 50.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - LOCF visit | 20.3 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - LOCF visit | 55.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - week 12 | 27.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - week 16 | 12.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - Week 2 | 31.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - Week 4 | 49.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - Week 8 | 67.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - Week 12 | 74.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - Week 20 | 81.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - Week 24 | 83.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - LOCF visit | 79.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - week 2 | 13.2 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - week 4 | 25.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - week 8 | 41.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - week 12 | 52.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - week 16 | 52.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - week 20 | 58.5 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - week 24 | 58.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR50 - LOCF visit | 54.2 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - week 2 | 2.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - week 4 | 10.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - week 8 | 22.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR20 - Week 16 | 75.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - week 16 | 32.2 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - week 20 | 36.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - week 24 | 37.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR70 - LOCF visit | 33.9 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - week 2 | 0.9 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - week 4 | 1.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - week 8 | 7.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - week 12 | 8.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - week 20 | 13.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - week 24 | 16.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 | ACR90 - LOCF visit | 15.0 Percentage of participants |
Secondary
Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48
The definition of improvement of ACR core set of outcome measures includes an improvement equal or higher to the 20%, 50%, 70%, 90% compared to Baseline in both Swollen Joint Count (SJC) and Tender Joint Count (TJC) as well as in three out of five additional parameters: Physician's Global Assessment of disease activity VAS, patient's Global Assessment of disease activity VAS, patient's assessment of pain VAS, HAQ-DI, and acute phase reactant (either CRP or erythrocyte sedimentation rate \[ESR\]).
Time frame: From week 28 until week 48
Population: Analysis was conducted on the FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR20 - Week 48 | 96.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR90 - Week 48 | 45.2 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR90 - LOCF visit | 42.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR20 - Week 28 | 90.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR20 - Week 32 | 93.1 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR20 - Week 36 | 84.9 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR20 - Week 40 | 88.1 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR20 - Week 44 | 91.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR20 - LOCF visit | 95.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR50 - Week 28 | 79.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR50 - Week 32 | 85.1 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR50 - Week 36 | 74.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR50 - Week 40 | 79.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR50 - Week 44 | 80.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR50 - Week 48 | 88.1 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR50 - LOCF visit | 84.3 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR70 - Week 28 | 59.1 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR70 - Week 32 | 65.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR70 - Week 36 | 61.6 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR70 - Week 40 | 65.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR70 - Week 44 | 67.1 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR70 - Week 48 | 71.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR70 - LOCF visit | 68.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR90 - Week 28 | 27.3 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR90 - Week 32 | 35.6 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR90 - Week 36 | 33.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR90 - Week 40 | 41.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR90 - Week 44 | 34.1 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR50 - Week 44 | 78.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR70 - Week 36 | 62.9 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR90 - Week 32 | 31.1 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR90 - Week 48 | 32.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR50 - Week 48 | 79.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR90 - LOCF visit | 32.2 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR70 - Week 48 | 65.2 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR20 - Week 28 | 92.2 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR50 - LOCF visit | 78.9 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR20 - Week 32 | 94.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR90 - Week 40 | 29.5 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR20 - Week 36 | 91.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR70 - Week 28 | 57.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR20 - Week 40 | 93.2 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR70 - LOCF visit | 64.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR20 - Week 44 | 91.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR20 - Week 48 | 88.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR70 - Week 32 | 54.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR20 - LOCF visit | 87.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR90 - Week 36 | 30.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR50 - Week 28 | 81.1 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR90 - Week 28 | 32.2 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR50 - Week 32 | 83.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR70 - Week 40 | 59.1 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR50 - Week 36 | 83.1 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR90 - Week 44 | 27.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR50 - Week 40 | 81.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 | ACR70 - Week 44 | 59.6 Percentage of participants |
Secondary
Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48
The DAS 28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP) and general health status. For this study ESR was used to calculate the DAS 28 score.
Time frame: Week 48
Population: Analysis was conducted on the FAS
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 28 | 82.6 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 48 | 100 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 44 | 94.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 32 | 81.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | LOCF Visit | 91.3 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 36 | 90.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 40 | 85.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 48 | 89.1 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 40 | 81.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 36 | 76.9 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 44 | 87.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | LOCF Visit | 89.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 32 | 89.1 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 28 | 90.6 Percentage of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 40 | 77.3 Percentage of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 28 | 87.0 Percentage of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 32 | 78.3 Percentage of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 36 | 86.4 Percentage of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 44 | 77.3 Percentage of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 48 | 77.3 Percentage of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | LOCF Visit | 73.9 Percentage of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 36 | 86.4 Percentage of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | LOCF Visit | 73.1 Percentage of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 48 | 72.7 Percentage of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 32 | 82.1 Percentage of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 28 | 83.1 Percentage of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 44 | 78.8 Percentage of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 | Week 40 | 81.8 Percentage of participants |
Secondary
Percentages of Patients With Remission (CDAI<2.8) Until Week 24
Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter \[cm\] Visual Analog Scale \[VAS\] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Week 2 | 2.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Week 16 | 18.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Week 8 | 11.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Week 20 | 27.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Week 4 | 2.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Week 24 | 29.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Week 12 | 15.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | LOCF visit | 29.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Baseline visit | 0 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | LOCF visit | 29.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Baseline visit | 0 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Week 2 | 1.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Week 4 | 5.1 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Week 8 | 14.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Week 12 | 19.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Week 16 | 22.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Week 20 | 26.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 24 | Week 24 | 30.2 Percentage of participants |
Secondary
Percentages of Patients With Remission (CDAI<2.8) Until Week 48
Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter \[cm\] Visual Analog Scale \[VAS\] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
Time frame: From week 28 until week 48
Population: Analysis was conducted on the FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | Week 36 | 52.3 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | Week 44 | 50.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | Week 32 | 48.3 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | Week 48 | 59.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | Week 40 | 52.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | LOCF Visit | 57.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | Week 28 | 46.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | LOCF Visit | 60.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | Week 28 | 48.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | Week 32 | 45.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | Week 36 | 46.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | Week 40 | 45.5 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | Week 44 | 50.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (CDAI<2.8) Until Week 48 | Week 48 | 53.9 Percentage of participants |
Secondary
Percentages of Patients With Remission (SDAI<3.3) Until Week 24
Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity.
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Baseline visit | 0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Week 12 | 14.3 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Week 4 | 2.9 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Week 16 | 17.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Week 2 | 1.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Week 8 | 11.1 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Week 24 | 31.7 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | LOCF visit | 28.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Week 20 | 28.1 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | LOCF visit | 25.4 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Week 24 | 28.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Baseline visit | 0 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Week 2 | 1.9 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Week 4 | 4.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Week 8 | 14.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Week 12 | 18.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Week 16 | 22.2 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 24 | Week 20 | 25.8 Percentage of participants |
Secondary
Percentages of Patients With Remission (SDAI<3.3) Until Week 48
Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity.
Time frame: From week 28 until week 48
Population: Analysis was conducted on the FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | Week 32 | 48.8 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | Week 40 | 55.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | Week 28 | 50.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | Week 44 | 50.0 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | Week 36 | 53.5 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | Week 48 | 52.4 Percentage of participants |
| Phase 1: Tocilizumab Monotherapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | LOCF Visit | 51.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | Week 36 | 47.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | LOCF Visit | 47.8 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | Week 28 | 46.0 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | Week 32 | 45.6 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | Week 48 | 47.7 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | Week 40 | 44.3 Percentage of participants |
| Phase 1: Combination Therapy | Percentages of Patients With Remission (SDAI<3.3) Until Week 48 | Week 44 | 47.2 Percentage of participants |
Secondary
Safety: Number of Patients Reporting Adverse Events up to Week 24
Number of patients reporting any treatment emergent adverse event (TEAE), at least one TEAE of special interest, at least one serious TEAE, at least one TEAE leading to dose modification, at least one TEAE leading to discontinuation up to week 24
Time frame: From baseline to Week 24
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Safety: Number of Patients Reporting Adverse Events up to Week 24 | At least one TEAE of special interest | 2 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Safety: Number of Patients Reporting Adverse Events up to Week 24 | At least one TEAE leading to dose modification | 24 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Safety: Number of Patients Reporting Adverse Events up to Week 24 | At least one serious TEAE | 3 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Safety: Number of Patients Reporting Adverse Events up to Week 24 | At least one TEAE leading to discontinuation | 4 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Safety: Number of Patients Reporting Adverse Events up to Week 24 | Any treatment emergent adverse event (TEAE) | 52 Number of participants |
| Phase 1: Combination Therapy | Safety: Number of Patients Reporting Adverse Events up to Week 24 | At least one TEAE leading to discontinuation | 21 Number of participants |
| Phase 1: Combination Therapy | Safety: Number of Patients Reporting Adverse Events up to Week 24 | Any treatment emergent adverse event (TEAE) | 254 Number of participants |
| Phase 1: Combination Therapy | Safety: Number of Patients Reporting Adverse Events up to Week 24 | At least one TEAE of special interest | 13 Number of participants |
| Phase 1: Combination Therapy | Safety: Number of Patients Reporting Adverse Events up to Week 24 | At least one serious TEAE | 10 Number of participants |
| Phase 1: Combination Therapy | Safety: Number of Patients Reporting Adverse Events up to Week 24 | At least one TEAE leading to dose modification | 103 Number of participants |
Secondary
Safety: Number of Patients Reporting Adverse Events up to Week 48
Number of patients reporting any treatment emergent adverse event (TEAE), at least one TEAE of special interest, at least one serious TEAE, at least one TEAE leading to dose modification, at least one TEAE leading to discontinuation up to week 48
Time frame: From week 24 until week 48
Population: Analysis was conducted on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Tocilizumab Monotherapy | Safety: Number of Patients Reporting Adverse Events up to Week 48 | Any TEAE | 50 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one serious TEAE | 2 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE leading to discontinuation | 0 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE of special interest | 1 Number of participants |
| Phase 1: Tocilizumab Monotherapy | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE leading to dose modification | 15 Number of participants |
| Phase 1: Combination Therapy | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE of special interest | 2 Number of participants |
| Phase 1: Combination Therapy | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one serious TEAE | 1 Number of participants |
| Phase 1: Combination Therapy | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE leading to dose modification | 23 Number of participants |
| Phase 1: Combination Therapy | Safety: Number of Patients Reporting Adverse Events up to Week 48 | Any TEAE | 63 Number of participants |
| Phase 1: Combination Therapy | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE leading to discontinuation | 0 Number of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one serious TEAE | 2 Number of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Safety: Number of Patients Reporting Adverse Events up to Week 48 | Any TEAE | 68 Number of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE of special interest | 2 Number of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE leading to dose modification | 23 Number of participants |
| Phase 2 Arm A2 - Monotherapy - q2w | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE leading to discontinuation | 0 Number of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE of special interest | 4 Number of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE leading to discontinuation | 2 Number of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE leading to dose modification | 21 Number of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Safety: Number of Patients Reporting Adverse Events up to Week 48 | Any TEAE | 46 Number of participants |
| Phase 2 Arm A2 - Combination Therapy - q2w | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one serious TEAE | 5 Number of participants |
| Phase 2 Arm D: Non Responders | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE of special interest | 0 Number of participants |
| Phase 2 Arm D: Non Responders | Safety: Number of Patients Reporting Adverse Events up to Week 48 | Any TEAE | 1 Number of participants |
| Phase 2 Arm D: Non Responders | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one serious TEAE | 1 Number of participants |
| Phase 2 Arm D: Non Responders | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE leading to discontinuation | 0 Number of participants |
| Phase 2 Arm D: Non Responders | Safety: Number of Patients Reporting Adverse Events up to Week 48 | At least one TEAE leading to dose modification | 1 Number of participants |