Rheumatoid Arthritis
Conditions
Brief summary
A multi-center, open-label single-arm study to evaluate the efficacy and safety of tocilizumab administered as a single, weekly injection in adults with rheumatoid arthritis. Combination therapy with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) was permitted.
Interventions
BIOLOGICALtocilizumab
162 milligram (mg) administered subcutaneously once weekly for 24 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults \>/= 18 years of age * Diagnosis of active rheumatoid arthritis (RA) according to the revised (1987) American College of Rheumatology (ACR) criteria or European League Against Rheumatism (EULAR)/ACR (2010) criteria * Previously treated with the following: three non-biologic DMARDs, and not treated with any biologic agent OR one biologic agent (alone or in combination with non-biologic DMARDs), and discontinued that agent for a reason * Oral corticosteroids (\</= 10 mg/day prednisone or equivalent), non-steroidal anti-inflammatory drug (NSAIDs) and non-biologic DMARDs are permitted if on a stable dose regimen for \>/= 4 weeks prior to Baseline * Use of effective contraception throughout the study as defined by protocol; female patients of childbearing potential must not be pregnant
Exclusion criteria
* Presence of serious, uncontrolled, clinically significant medical conditions * History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal (GI) disease that might predispose to perforation * Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections * Any infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening * Clinically significant findings on lab tests and/or hepatitis B or C, or human immunodeficiency virus (HIV) screenings * Active tuberculosis (TB) requiring treatments within the previous 3 years * Evidence of active malignant disease, malignancies diagnosed within the previous 10 years, or breast cancer diagnosed within the previous 20 years * History of alcohol, drug, or chemical abuse within 1 year prior to Screening * Neuropathies or other conditions that might interfere with pain evaluation * 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, including systemic lupus erythematosus, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). 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 IV or subcutaneous administration) at any time prior to Baseline * Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of Screening * Previous treatment with any cell-depleting therapies, including investigational agents approved therapies, with alkylating agents such as chlorambucil, or with total lymphoid irradiation * Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline * Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission and CDAI Low Disease Activity | 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. Remission is defined as CDAI ≤2.8 and Low Disease Activity (LDA) is defined as 2.8\< CDAI ≤10. |
| Change From Baseline in CDAI | Baseline, 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 Participants With Simplified Disease Activity Index (SDAI) Remission and SDAI Low Disease Activity | Week 24 | Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in milligram/liter (mg/L). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. An SDAI score of ≤ 3.3 represents clinical remission, a score of ≤ 11.0 represents low disease activity. |
| Change From Baseline in SDAI | Baseline, Week 24 | Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in mg/L. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A negative change from baseline indicates an improvement. |
| Change From Baseline in Disease Activity Score 28-Erythrocyte-Sedimentation Rate (DAS28-ESR) | Baseline, Week 24 | The DAS28-ESR score is a measure of the patient's disease activity calculated using the tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), patient's global assessment (PGA) of disease activity based on visual analog scale (VAS) and the erythrocyte sedimentation rate (ESR) in millimeter/hour (mm/hr). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total possible score ranged from 0 to 10. Higher scores represent higher disease activity. A negative change from baseline indicates an improvement. |
| Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70) | Week 24 | An ACR20 response requires at least 20% improvement compared to baseline in SJC (based on 66 joints) and TJC (based on 68 joints) as well as at least 20% improvement in 3 of the following 5 assessments: 1) PGA pain VAS, 2) PGA VAS; 3) physician's global assessment of disease activity VAS, 4) Health Assessment Questionnaire-Disability Index (HAQ-DI) with 20 questions consisting of 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do; and 5) CRP in mg/L or ESR in mm/hr. ACR50 and ACR70 responses are defined in a similar way except that they required a 50% and 70% improvement from baseline, respectively. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). |
| Percentage of Participants With Good to Moderate European League Against Rheumatism (EULAR) Response | Week 24 | Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit. Participants with a score lesser than or equal to (\</=) 3.2 and reduction of greater than (\>) 1.2 points were assessed as having a 'good' response. Participants with a score \>3.2 with reduction of \>1.2 points, or a score \<=5.1 with reduction of \>0.6 to \<=1.2 points, were assessed as having a 'moderate' response. Participants with a score \>5.1 with reduction of \>0.6 to \<=1.2 points, or any score with reduction \<=0.6 points, were assessed as non-responders with response recorded as 'none.' |
| Change From Baseline in TJC and SJC | Baseline, Week 24 | The number of tender joints (based on 68 joints) and swollen joints (based on 66 joints) were counted at each visit. TJC was determined by identifying the joints that were painful under pressure or to passive motion; no tenderness =0, tenderness =1. SJC was determined by identifying swelling; no swelling =0, swelling =1. A negative change from baseline indicates an improvement. |
| Change From Baseline in Percentage of Participants on Tocilizumab Monotherapy | Baseline, Week 24 | Participants were either on tocilizumab monotherapy or tocilizumab plus non-biologic disease modifying anti-rheumatic drugs (DMARDs). Reported here is the percentage of participants on tocilizumab monotherapy at baseline and the change from baseline at Week 24. A positive change from baseline at Week 24 indicates the percentage of participants, who discontinued DMARDs during the study. |
| Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (PGA VAS) | Baseline, Week 24 | PGA VAS represents the participant's overall assessment of their current disease activity on a 100 millimeter (mm) horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement. |
| Change From Baseline in Patient Pain VAS | Baseline, Week 24 | Patient Pain VAS represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement. |
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) | Baseline, Week 24 | The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities and 20 questions. Each category contains multiple questions, which were answered using a 4-point scale from 0 (without any difficulty) to 3 (unable to do). The overall index score was an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. A negative change from baseline indicates an improvement. |
| Change From Baseline in Patient Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) | Baseline, 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 52. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions. A positive change from baseline indicates an improvement. |
| Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) | Baseline, Week 24 | The HDRS is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. A higher score indicates a worse outcome. HAS is a clinician-administered assessment to measure the severity of anxiety symptoms and consists of 14 items with a total score range from 0 to 56. A higher score indicates a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) and AEs of Special Interest (AESIs) | Up to Follow-up Week 32 | An AE is any untoward medical occurrence in a participant administered a drug and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, whether or not considered related to the drug. Preexisting conditions which worsen during a study are also considered as AEs. AESIs are AEs that occur in categories of special interest with regard to the benefit-risk profile and overall safety of a drug. The following nine categories of AESIs were identified for tocilizumab: 1) serious and/or medically significant infections, 2) myocardial infarction/acute coronary syndrome, 3) gastrointestinal perforations, 4) malignancies, 5) anaphylaxis/hypersensitivity reactions, 6) demyelinating disorders, 7) stroke, 8) serious and/or medically significant bleeding events, and 9) serious and/or medically significant hepatic events. |
| Percentage of Participants Who Required Dose Modifications or Discontinued Study Due to AEs | Up to Week 24 | — |
| Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies | Baseline, Week 24, Follow-up Week 32 and Early Withdrawal | Reported is the percentage of participants positive for anti-tocilizumab antibodies in the confirmatory anti-tocilizumab antibody assay, which followed an initial anti-tocilizumab screen. Participants, who withdrew from the study |
| Immunogenicity: Tocilizumab Levels | Week 12, Week 24, Follow-up Week 32 and Early Withdrawal | — |
| Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels | Week 1, Week 12, Week 24, Follow-up Week 32 and Early Withdrawal | A positive change from Week 1 indicates an increase in sIL-6R levels. |
Countries
Israel
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended. | 100 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Insufficient Therapeutic Response | 3 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Patient Withdrawal of Consent | 4 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Tocilizumab |
|---|---|
| Age, Continuous | 54.3 years STANDARD_DEVIATION 11.8 |
| Gender Female | 80 Participants |
| Gender Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 44 / 100 |
| serious Total, serious adverse events | 6 / 100 |
Outcome results
Primary
Change From Baseline in CDAI
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: Baseline, Week 24
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in CDAI | Baseline | 31.89 units on a scale | Standard Deviation 14.35 |
| Tocilizumab | Change From Baseline in CDAI | Change from Baseline at Week 24 | -18.29 units on a scale | Standard Deviation 14.52 |
Primary
Change From Baseline in Disease Activity Score 28-Erythrocyte-Sedimentation Rate (DAS28-ESR)
The DAS28-ESR score is a measure of the patient's disease activity calculated using the tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), patient's global assessment (PGA) of disease activity based on visual analog scale (VAS) and the erythrocyte sedimentation rate (ESR) in millimeter/hour (mm/hr). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total possible score ranged from 0 to 10. Higher scores represent higher disease activity. A negative change from baseline indicates an improvement.
Time frame: Baseline, Week 24
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in Disease Activity Score 28-Erythrocyte-Sedimentation Rate (DAS28-ESR) | Baseline | 4.98 units on a scale | Standard Deviation 0.98 |
| Tocilizumab | Change From Baseline in Disease Activity Score 28-Erythrocyte-Sedimentation Rate (DAS28-ESR) | Change from Baseline at Week 24 | -2.47 units on a scale | Standard Deviation 1.29 |
Primary
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities and 20 questions. Each category contains multiple questions, which were answered using a 4-point scale from 0 (without any difficulty) to 3 (unable to do). The overall index score was an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. A negative change from baseline indicates an improvement.
Time frame: Baseline, Week 24
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) | Baseline | 1.55 units on a scale | Standard Deviation 0.8 |
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) | Change from Baseline at Week 24 | -0.34 units on a scale | Standard Deviation 0.62 |
Primary
Change From Baseline in Patient Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
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 52. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions. A positive change from baseline indicates an improvement.
Time frame: Baseline, Week 24
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in Patient Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) | Baseline | 23.46 units on a scale | Standard Deviation 11.32 |
| Tocilizumab | Change From Baseline in Patient Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) | Change from Baseline at Week 24 | 6.95 units on a scale | Standard Deviation 9.7 |
Primary
Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (PGA VAS)
PGA VAS represents the participant's overall assessment of their current disease activity on a 100 millimeter (mm) horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement.
Time frame: Baseline, Week 24
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (PGA VAS) | Baseline | 69.73 units on a scale | Standard Deviation 24.55 |
| Tocilizumab | Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (PGA VAS) | Change from Baseline at Week 24 | -31.22 units on a scale | Standard Deviation 28.43 |
Primary
Change From Baseline in Patient Pain VAS
Patient Pain VAS represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement.
Time frame: Baseline, Week 24
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in Patient Pain VAS | Baseline | 64.82 units on a scale | Standard Deviation 26.39 |
| Tocilizumab | Change From Baseline in Patient Pain VAS | Change from Baseline at Week 24 | -29.11 units on a scale | Standard Deviation 29.16 |
Primary
Change From Baseline in Percentage of Participants on Tocilizumab Monotherapy
Participants were either on tocilizumab monotherapy or tocilizumab plus non-biologic disease modifying anti-rheumatic drugs (DMARDs). Reported here is the percentage of participants on tocilizumab monotherapy at baseline and the change from baseline at Week 24. A positive change from baseline at Week 24 indicates the percentage of participants, who discontinued DMARDs during the study.
Time frame: Baseline, Week 24
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Change From Baseline in Percentage of Participants on Tocilizumab Monotherapy | Baseline | 26 percentage of participants |
| Tocilizumab | Change From Baseline in Percentage of Participants on Tocilizumab Monotherapy | Change from Baseline at Week 24 | 12 percentage of participants |
Primary
Change From Baseline in SDAI
Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in mg/L. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A negative change from baseline indicates an improvement.
Time frame: Baseline, Week 24
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in SDAI | Baseline | 33.73 units on a scale | Standard Deviation 14.83 |
| Tocilizumab | Change From Baseline in SDAI | Change from Baseline at Week 24 | -21.41 units on a scale | Standard Deviation 14.99 |
Primary
Change From Baseline in TJC and SJC
The number of tender joints (based on 68 joints) and swollen joints (based on 66 joints) were counted at each visit. TJC was determined by identifying the joints that were painful under pressure or to passive motion; no tenderness =0, tenderness =1. SJC was determined by identifying swelling; no swelling =0, swelling =1. A negative change from baseline indicates an improvement.
Time frame: Baseline, Week 24
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in TJC and SJC | TJC at Baseline | 21.42 joint count | Standard Deviation 15.2 |
| Tocilizumab | Change From Baseline in TJC and SJC | TJC Change from Baseline at Week 24 | -11.91 joint count | Standard Deviation 13.59 |
| Tocilizumab | Change From Baseline in TJC and SJC | SJC at Baseline | 10.30 joint count | Standard Deviation 10.27 |
| Tocilizumab | Change From Baseline in TJC and SJC | SJC Change from Baseline at Week 24 | -7.54 joint count | Standard Deviation 9.6 |
Primary
Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70)
An ACR20 response requires at least 20% improvement compared to baseline in SJC (based on 66 joints) and TJC (based on 68 joints) as well as at least 20% improvement in 3 of the following 5 assessments: 1) PGA pain VAS, 2) PGA VAS; 3) physician's global assessment of disease activity VAS, 4) Health Assessment Questionnaire-Disability Index (HAQ-DI) with 20 questions consisting of 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do; and 5) CRP in mg/L or ESR in mm/hr. ACR50 and ACR70 responses are defined in a similar way except that they required a 50% and 70% improvement from baseline, respectively. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity).
Time frame: Week 24
Population: The analysis population included those participants from the FAS for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70) | ACR20 | 62.4 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70) | ACR50 | 37.6 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70) | ACR70 | 20.0 percentage of participants |
Primary
Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission and CDAI Low Disease Activity
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. Remission is defined as CDAI ≤2.8 and Low Disease Activity (LDA) is defined as 2.8\< CDAI ≤10.
Time frame: Week 24
Population: The analysis population included those participants from the full analysis set (FAS) for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission and CDAI Low Disease Activity | CDAI Remission | 16.5 percentage of participants |
| Tocilizumab | Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission and CDAI Low Disease Activity | CDAI LDA | 34.1 percentage of participants |
Primary
Percentage of Participants With Good to Moderate European League Against Rheumatism (EULAR) Response
Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit. Participants with a score lesser than or equal to (\</=) 3.2 and reduction of greater than (\>) 1.2 points were assessed as having a 'good' response. Participants with a score \>3.2 with reduction of \>1.2 points, or a score \<=5.1 with reduction of \>0.6 to \<=1.2 points, were assessed as having a 'moderate' response. Participants with a score \>5.1 with reduction of \>0.6 to \<=1.2 points, or any score with reduction \<=0.6 points, were assessed as non-responders with response recorded as 'none.'
Time frame: Week 24
Population: The analysis population included those participants from the FAS for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants With Good to Moderate European League Against Rheumatism (EULAR) Response | 96.4 percentage of participants |
Primary
Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission and SDAI Low Disease Activity
Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in milligram/liter (mg/L). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. An SDAI score of ≤ 3.3 represents clinical remission, a score of ≤ 11.0 represents low disease activity.
Time frame: Week 24
Population: The analysis population included those participants from the FAS for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission and SDAI Low Disease Activity | SDAI Remission | 19.2 percentage of participants |
| Tocilizumab | Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission and SDAI Low Disease Activity | SDAI LDA | 38.5 percentage of participants |
Primary
Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS)
The HDRS is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. A higher score indicates a worse outcome. HAS is a clinician-administered assessment to measure the severity of anxiety symptoms and consists of 14 items with a total score range from 0 to 56. A higher score indicates a worse outcome.
Time frame: Baseline, Week 24
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) | HDRS at Baseline | 7.87 units on a scale | Standard Deviation 7.19 |
| Tocilizumab | Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) | HDRS at Week 24 | 4.94 units on a scale | Standard Deviation 5.85 |
| Tocilizumab | Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) | HAS at Baseline | 8.56 units on a scale | Standard Deviation 8.43 |
| Tocilizumab | Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) | HAS at Week 24 | 5.93 units on a scale | Standard Deviation 7.17 |
Secondary
Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels
A positive change from Week 1 indicates an increase in sIL-6R levels.
Time frame: Week 1, Week 12, Week 24, Follow-up Week 32 and Early Withdrawal
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels | Week 1 | 38.33 nanograms/milliliter (ng/mL) | Standard Deviation 10.3 |
| Tocilizumab | Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels | Change from Week 1 at Week 12 | 475.79 nanograms/milliliter (ng/mL) | Standard Deviation 120.98 |
| Tocilizumab | Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels | Change from Week 1 at Week 24 | 503.67 nanograms/milliliter (ng/mL) | Standard Deviation 127.13 |
| Tocilizumab | Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels | Change from Week 1 at Follow-up at Week 32 | 382.26 nanograms/milliliter (ng/mL) | Standard Deviation 240.95 |
| Tocilizumab | Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels | Change from Week 1 at Early withdrawal | 309.91 nanograms/milliliter (ng/mL) | Standard Deviation 183.07 |
Secondary
Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies
Reported is the percentage of participants positive for anti-tocilizumab antibodies in the confirmatory anti-tocilizumab antibody assay, which followed an initial anti-tocilizumab screen. Participants, who withdrew from the study
Time frame: Baseline, Week 24, Follow-up Week 32 and Early Withdrawal
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies | Early Withdrawal | 0 percentage of participants |
| Tocilizumab | Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies | Baseline | 1.0 percentage of participants |
| Tocilizumab | Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies | Week 24 | 0 percentage of participants |
| Tocilizumab | Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies | Follow-up Visit Week 32 | 0 percentage of participants |
Secondary
Immunogenicity: Tocilizumab Levels
Time frame: Week 12, Week 24, Follow-up Week 32 and Early Withdrawal
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Immunogenicity: Tocilizumab Levels | Week 12 | 35.49 microgram/milliliter (mcg/mL) | Standard Deviation 17.81 |
| Tocilizumab | Immunogenicity: Tocilizumab Levels | Week 24 | 41.63 microgram/milliliter (mcg/mL) | Standard Deviation 22.79 |
| Tocilizumab | Immunogenicity: Tocilizumab Levels | Follow-up Week 32 | 39.53 microgram/milliliter (mcg/mL) | Standard Deviation 28.47 |
| Tocilizumab | Immunogenicity: Tocilizumab Levels | Early withdrawal | 19.04 microgram/milliliter (mcg/mL) | Standard Deviation 15.69 |
Secondary
Percentage of Participants Who Required Dose Modifications or Discontinued Study Due to AEs
Time frame: Up to Week 24
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Who Required Dose Modifications or Discontinued Study Due to AEs | % of Particpants with Dose Modifications | 16 percentage of participants |
| Tocilizumab | Percentage of Participants Who Required Dose Modifications or Discontinued Study Due to AEs | % of Participants Who Discontinued Study | 5 percentage of participants |
Secondary
Percentage of Participants With Adverse Events (AEs) and AEs of Special Interest (AESIs)
An AE is any untoward medical occurrence in a participant administered a drug and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, whether or not considered related to the drug. Preexisting conditions which worsen during a study are also considered as AEs. AESIs are AEs that occur in categories of special interest with regard to the benefit-risk profile and overall safety of a drug. The following nine categories of AESIs were identified for tocilizumab: 1) serious and/or medically significant infections, 2) myocardial infarction/acute coronary syndrome, 3) gastrointestinal perforations, 4) malignancies, 5) anaphylaxis/hypersensitivity reactions, 6) demyelinating disorders, 7) stroke, 8) serious and/or medically significant bleeding events, and 9) serious and/or medically significant hepatic events.
Time frame: Up to Follow-up Week 32
Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Adverse Events (AEs) and AEs of Special Interest (AESIs) | AEs | 70.0 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs) and AEs of Special Interest (AESIs) | AESIs | 7.0 percentage of participants |