Rheumatoid Arthritis
Conditions
Brief summary
This open label, single arm study will assess the safety and efficacy of RoActemra/Actemra (tocilizumab) in patients with moderate to severe active rheumatoid arthritis who have an inadequate response to disease-modifying antirheumatic drugs (DMARDs). Patients will receive RoActemra/Actemra at a dose of 8 mg/kg intravenously every 4 weeks for 24 weeks (6 infusions).
Interventions
DRUGtocilizumab [RoActemra/Actemra]
8 mg/kg iv every 4 weeks, total of 6 infusions
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
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 * Moderate to severe active rheumatoid arthritis (DAS28 \> 3.2 at screening) * Inadequate response to DMARDs * Body weight \< 150 kg
Exclusion criteria
* Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months of enrollment * Rheumatic autoimmune disease other than RA * American College of Rheumatology (ACR) functional class IV * Prior history of or current inflammatory joint disease other than RA * Previous treatment with any biologic drug that is used in the treatment of RA * Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline * Pregnant or lactating women * Active current or history of recurrent infection, active TB within the previous 3 years, HIV infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | Percentage of participants with adverse events (AEs), serious adverse events (SAEs), severe AEs, AEs leading to withdrawal, AEs leading to death, and treatment-related AEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) to Highest Value | Baseline through Week 24 | The difference between baseline and highest values until Week 24 of ALT and AST. The values are measures as international units per liter (UI/L). The change was calculated as the value (highest) at a later timepoint up to Week 24, minus the value at Baseline. |
| Change From Baseline Low-Density Lipoprotein (LDL) and Total Cholesterol (TC) to Highest Values | Baseline through Week 24 | Levels of LDL and TC were measured in milligrams/deciliter (mg/dL). Change in LDL and TC were calculated as the value (highest) through Week 24, minus the value at Baseline. |
| Percentage of Participants With Lipid Elevations by Study Visit | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | Lipid panel assessed included TC, triglycerides, high-density lipoprotein (HDL), and LDL. Elevations were categorized as follows: LDL cholesterol: Optimal equals (=) less than (\<)100 mg/dL, Near optimal=100-129 mg/dL, Borderline high 130-159 mg/dL, High 160-189 mg/dL, Very High ≥190 mg/dL; Total cholesterol: Desirable \<200 mg/dL, Borderline high 200-239 mg/dL, High ≥240 mg/dL; HDL cholesterol: Low \<40 mg/dL, High ≥60 mg/dL; Triglycerides: Normal \<150 mg/dL, Borderline high 150-199 mg/dL, High 200-499 mg/dL, and Very high ≥500 mg/dL. |
| Disease Activity Score Based on 28-Joint Count (DAS28) | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR; in millimeters per hour \[mm/hour\]) and global health assessment (participant-rated global assessment of disease activity using 10-mm visual analog assessment \[VAS\]); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 less than or equal to (≤3.2) = low disease activity, DAS28 greater than (\>)3.2 to less than or equal to (≤) 5.1=moderate to high disease activity; DAS28 \>5.1=high disease activity. |
| Percentage of Participants by DAS28 Response Category | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 ≤3.2 =low disease activity, DAS28 \>3.2 to ≤5.1=moderate to high disease activity; DAS28 \>5.1=high disease activity. |
| Percentage of Participants With a Clinically Meaningful Improvement in Disease Activity | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. A reduction in DAS28 of at least 1.2 units was considered a clinically meaningful improvement. |
| Time to Achieve Clinically Meaningful Reduction in DAS28 | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | A clinically meaningful improvement in DAS28 was defined as a reduction of at least 1.2 units. Time to achieving clinically meanigful improvement was calculated as the number of days from the first infusion to the first achievement of reduction of 1.2 units in DAS28. |
| Percentage of Participants Achieving Remission (DAS28 <2.6) | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Participants with a DAS28 score \<2.6 were considered to have achieved remission. |
| Percentage of Participants With All-Cause Discontinuation of Tocilizumab by Study Visit | Weeks 4, 8, 12, 16, 20, and 24 | Percentage of participants discontinuing study treatment for any reason at every visit; causes of discontinuation in the summary included AEs, deaths, lost to follo-wup, AE and investigator decision and 'not determined'. |
| Swollen and Tender Joint Counts | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | The following 28 joints were assessed by the physician for swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). The following 28 joints were assessed by the physician for tenderness : metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). The change in SJC and TJC was determined as the difference in values from baseline at each visit. |
| Health Assessment Questionnaire (HAQ) | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | HAQ was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple-choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from 4 response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The change in HAQ was determined as the difference in values from baseline at each visit. |
| Patient Global Assessment of Disease Activity (VAS) | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | The participant's overall assessment of their current disease activity was displayed on a 100-mm horizontal VAS. The left-hand extreme (0 mm) of the line was described as no disease activity (symptom free and no arthritis symptoms) and the right-hand extreme (100 mm) was described as maximum disease activity (maximum arthritis disease activity). The change in Patient Global Assessment of Disease Activity was determined as the difference in values from baseline at each visit. |
| Physician's Global Assessment of Disease Activity (VAS) | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | The physician's assessment of the participant's current disease activity was displayed on a 100-mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme (100 mm) was described as maximum disease activity. The Physician's Global Assessment of Disease Activity was completed by the Efficacy Assessor who could or could not be a physician. The change in Physician's Global Assessment of Disease Activity was determined as the difference in values from baseline at each visit. |
| Patient Assessment of of Pain (VAS) | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | The participant's assessment of their current level of pain was displayed on a 100-mm horizontal VAS. The left-hand extreme (0 mm) of the line was described as no pain and the right-hand extreme of the line (100 mm) was described as unbearable pain. The change in participant's perception of pain was determined as the difference in values from baseline at each visit. |
| C-Reactive Protein (CRP) | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | CRP is an acute phase inflammatory marker. Levels of CRP increase with inflammation. The change in CRP was determined as the difference in values from baseline and at each visit. |
| Erythrocyte Sedimentation Rate (ESR) | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | ESR indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. The change in ESR was determined as the difference in values from baseline at each visit. |
| Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | Weeks 4, 8, 12, 16, 20, and 24 | The ACR response rates ACR20, ACR50, ACR70 are defined as ≥20%, ≥50%, ≥70% improvement, respectively, in: swollen joint count (SJC) (66 joints) and tender joint count (TJC) (68 joints) and 3 of the following 5 assessments: Patient assessment of pain (VAS); Patient global assessment of disease activity (VAS); Investigator global assessment of disease activity (VAS); and acute phase response (ESR or CRP) |
Countries
Morocco
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab 8 mg/kg Participants received tocilizumab 8 mg/kg, IV, once every 4 weeks for a total of 6 infusions. | 117 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Adverse event and Investigator decision | 1 |
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Not determined | 5 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Tocilizumab 8 mg/kg |
|---|---|
| Age, Continuous | 46.3 years STANDARD_DEVIATION 12.5 |
| Sex: Female, Male Female | 96 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 59 / 121 |
| serious Total, serious adverse events | 13 / 121 |
Outcome results
Primary
Percentage of Participants With Adverse Events
Percentage of participants with adverse events (AEs), serious adverse events (SAEs), severe AEs, AEs leading to withdrawal, AEs leading to death, and treatment-related AEs.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: Safety population: all participants who received at least one dose of study medication where at least one post-baseline assessment of safety was available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab 8 mg/kg | Percentage of Participants With Adverse Events | AEs | 48.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Adverse Events | SAEs | 10.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Adverse Events | With severe AEs | 8.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Adverse Events | AEs leading to withdrawals | 5.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Adverse Events | AEs leading to death | 0.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Adverse Events | Treatment-related AEs | 10.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Adverse Events | Treatment-related SAEs | 4.1 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Adverse Events | Treatment-related severe AEs | 5.0 percentage of participants |
Secondary
Change From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) to Highest Value
The difference between baseline and highest values until Week 24 of ALT and AST. The values are measures as international units per liter (UI/L). The change was calculated as the value (highest) at a later timepoint up to Week 24, minus the value at Baseline.
Time frame: Baseline through Week 24
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab 8 mg/kg | Change From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) to Highest Value | ALT | 23.6 UI/L | Standard Deviation 34.7 |
| Tocilizumab 8 mg/kg | Change From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) to Highest Value | AST | 15.8 UI/L | Standard Deviation 22.1 |
Comparison: Difference in ALT from Baseline to Week 24p-value: <0.001t-test, 2 sided
Comparison: Difference in AST from Baseline to Week 24p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline Low-Density Lipoprotein (LDL) and Total Cholesterol (TC) to Highest Values
Levels of LDL and TC were measured in milligrams/deciliter (mg/dL). Change in LDL and TC were calculated as the value (highest) through Week 24, minus the value at Baseline.
Time frame: Baseline through Week 24
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab 8 mg/kg | Change From Baseline Low-Density Lipoprotein (LDL) and Total Cholesterol (TC) to Highest Values | Total cholesterol | 57.2 mg/dL | Standard Deviation 78.1 |
| Tocilizumab 8 mg/kg | Change From Baseline Low-Density Lipoprotein (LDL) and Total Cholesterol (TC) to Highest Values | LDL cholesterol | 108.6 mg/dL | Standard Deviation 106.2 |
Comparison: Diffrence in total cholesterol from baseline to Week 24p-value: <0.001t-test, 2 sided
Comparison: Difference in LDL cholesterol from baseline to Week 24p-value: <0.001t-test, 2 sided
Secondary
C-Reactive Protein (CRP)
CRP is an acute phase inflammatory marker. Levels of CRP increase with inflammation. The change in CRP was determined as the difference in values from baseline and at each visit.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab 8 mg/kg | C-Reactive Protein (CRP) | Baseline | 22.9 mg/dL | Standard Deviation 24.1 |
| Tocilizumab 8 mg/kg | C-Reactive Protein (CRP) | Week 4 | 6.5 mg/dL | Standard Deviation 14.8 |
| Tocilizumab 8 mg/kg | C-Reactive Protein (CRP) | Change at Week 4 | 16.6 mg/dL | Standard Deviation 27.3 |
| Tocilizumab 8 mg/kg | C-Reactive Protein (CRP) | Week 8 | 4.9 mg/dL | Standard Deviation 6.4 |
| Tocilizumab 8 mg/kg | C-Reactive Protein (CRP) | Change at Week 8 | 17.7 mg/dL | Standard Deviation 23.1 |
| Tocilizumab 8 mg/kg | C-Reactive Protein (CRP) | Week 12 | 5.1 mg/dL | Standard Deviation 9.4 |
| Tocilizumab 8 mg/kg | C-Reactive Protein (CRP) | Change at Week 12 | 16.8 mg/dL | Standard Deviation 24.3 |
| Tocilizumab 8 mg/kg | C-Reactive Protein (CRP) | Week 16 | 5.2 mg/dL | Standard Deviation 7.5 |
| Tocilizumab 8 mg/kg | C-Reactive Protein (CRP) | Change at Week 16 | 17.2 mg/dL | Standard Deviation 23.3 |
| Tocilizumab 8 mg/kg | C-Reactive Protein (CRP) | Week 20 | 6.1 mg/dL | Standard Deviation 11.6 |
| Tocilizumab 8 mg/kg | C-Reactive Protein (CRP) | Change at Week 20 | 16.0 mg/dL | Standard Deviation 24.1 |
| Tocilizumab 8 mg/kg | C-Reactive Protein (CRP) | Week 24 | 6.7 mg/dL | Standard Deviation 8.7 |
| Tocilizumab 8 mg/kg | C-Reactive Protein (CRP) | Change at Week 24 | 16.1 mg/dL | Standard Deviation 24.3 |
Secondary
Disease Activity Score Based on 28-Joint Count (DAS28)
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR; in millimeters per hour \[mm/hour\]) and global health assessment (participant-rated global assessment of disease activity using 10-mm visual analog assessment \[VAS\]); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 less than or equal to (≤3.2) = low disease activity, DAS28 greater than (\>)3.2 to less than or equal to (≤) 5.1=moderate to high disease activity; DAS28 \>5.1=high disease activity.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab 8 mg/kg | Disease Activity Score Based on 28-Joint Count (DAS28) | Baseline (n=117) | 6.2 units on a scale | Standard Deviation 1.5 |
| Tocilizumab 8 mg/kg | Disease Activity Score Based on 28-Joint Count (DAS28) | Week 4 (n=116) | 4.0 units on a scale | Standard Deviation 1.6 |
| Tocilizumab 8 mg/kg | Disease Activity Score Based on 28-Joint Count (DAS28) | Week 8 (n=112) | 3.3 units on a scale | Standard Deviation 1.4 |
| Tocilizumab 8 mg/kg | Disease Activity Score Based on 28-Joint Count (DAS28) | Week 12 (n=109) | 2.8 units on a scale | Standard Deviation 1.4 |
| Tocilizumab 8 mg/kg | Disease Activity Score Based on 28-Joint Count (DAS28) | Week 16 (n=106) | 2.4 units on a scale | Standard Deviation 1.4 |
| Tocilizumab 8 mg/kg | Disease Activity Score Based on 28-Joint Count (DAS28) | Week 20 (n=103) | 2.1 units on a scale | Standard Deviation 1.2 |
| Tocilizumab 8 mg/kg | Disease Activity Score Based on 28-Joint Count (DAS28) | Week 24 (n=99) | 2.0 units on a scale | Standard Deviation 1.3 |
Secondary
Erythrocyte Sedimentation Rate (ESR)
ESR indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. The change in ESR was determined as the difference in values from baseline at each visit.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab 8 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Baseline | 31.4 mm/hr | Standard Deviation 23.3 |
| Tocilizumab 8 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 4 | 9.5 mm/hr | Standard Deviation 11.7 |
| Tocilizumab 8 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Change at Week 4 | 21.8 mm/hr | Standard Deviation 20.1 |
| Tocilizumab 8 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 8 | 8.3 mm/hr | Standard Deviation 11.6 |
| Tocilizumab 8 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Change at Week 8 | 22.4 mm/hr | Standard Deviation 20.7 |
| Tocilizumab 8 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 12 | 8.6 mm/hr | Standard Deviation 12 |
| Tocilizumab 8 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Change at Week 12 | 22.9 mm/hr | Standard Deviation 21.3 |
| Tocilizumab 8 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 16 | 8.1 mm/hr | Standard Deviation 13 |
| Tocilizumab 8 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Change at Week 16 | 23.0 mm/hr | Standard Deviation 18.9 |
| Tocilizumab 8 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 20 | 7.8 mm/hr | Standard Deviation 11.3 |
| Tocilizumab 8 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Change at Week 20 | 22.4 mm/hr | Standard Deviation 19.4 |
| Tocilizumab 8 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 24 | 8.2 mm/hr | Standard Deviation 9.7 |
| Tocilizumab 8 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Change at Week 24 | 22.2 mm/hr | Standard Deviation 2.4 |
Secondary
Health Assessment Questionnaire (HAQ)
HAQ was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple-choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from 4 response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The change in HAQ was determined as the difference in values from baseline at each visit.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab 8 mg/kg | Health Assessment Questionnaire (HAQ) | Baseline | 1.97 score on a scale | Standard Deviation 0.82 |
| Tocilizumab 8 mg/kg | Health Assessment Questionnaire (HAQ) | Week 4 | 1.44 score on a scale | Standard Deviation 0.83 |
| Tocilizumab 8 mg/kg | Health Assessment Questionnaire (HAQ) | Change at Week 4 | 0.52 score on a scale | Standard Deviation 0.55 |
| Tocilizumab 8 mg/kg | Health Assessment Questionnaire (HAQ) | Week 8 | 1.02 score on a scale | Standard Deviation 0.73 |
| Tocilizumab 8 mg/kg | Health Assessment Questionnaire (HAQ) | Change at Week 8 | 0.94 score on a scale | Standard Deviation 0.72 |
| Tocilizumab 8 mg/kg | Health Assessment Questionnaire (HAQ) | Week 12 | 0.80 score on a scale | Standard Deviation 0.7 |
| Tocilizumab 8 mg/kg | Health Assessment Questionnaire (HAQ) | Change at Week 12 | 1.14 score on a scale | Standard Deviation 0.79 |
| Tocilizumab 8 mg/kg | Health Assessment Questionnaire (HAQ) | Week 16 | 0.70 score on a scale | Standard Deviation 0.77 |
| Tocilizumab 8 mg/kg | Health Assessment Questionnaire (HAQ) | Change at Week 16 | 1.24 score on a scale | Standard Deviation 0.91 |
| Tocilizumab 8 mg/kg | Health Assessment Questionnaire (HAQ) | Week 20 | 0.56 score on a scale | Standard Deviation 0.66 |
| Tocilizumab 8 mg/kg | Health Assessment Questionnaire (HAQ) | Change at Week 20 | 1.33 score on a scale | Standard Deviation 0.86 |
| Tocilizumab 8 mg/kg | Health Assessment Questionnaire (HAQ) | HAQ Week 24 | 0.56 score on a scale | Standard Deviation 0.69 |
| Tocilizumab 8 mg/kg | Health Assessment Questionnaire (HAQ) | Change at Week 24 | 1.32 score on a scale | Standard Deviation 0.87 |
Secondary
Patient Assessment of of Pain (VAS)
The participant's assessment of their current level of pain was displayed on a 100-mm horizontal VAS. The left-hand extreme (0 mm) of the line was described as no pain and the right-hand extreme of the line (100 mm) was described as unbearable pain. The change in participant's perception of pain was determined as the difference in values from baseline at each visit.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab 8 mg/kg | Patient Assessment of of Pain (VAS) | Baseline | 63.4 mm | Standard Deviation 18.7 |
| Tocilizumab 8 mg/kg | Patient Assessment of of Pain (VAS) | Week 4 | 41.4 mm | Standard Deviation 21.1 |
| Tocilizumab 8 mg/kg | Patient Assessment of of Pain (VAS) | Change at Week 4 | 21.9 mm | Standard Deviation 20.7 |
| Tocilizumab 8 mg/kg | Patient Assessment of of Pain (VAS) | Week 8 | 29.1 mm | Standard Deviation 21 |
| Tocilizumab 8 mg/kg | Patient Assessment of of Pain (VAS) | Change at Week 8 | 34.5 mm | Standard Deviation 23.1 |
| Tocilizumab 8 mg/kg | Patient Assessment of of Pain (VAS) | Week 12 | 21.4 mm | Standard Deviation 18.1 |
| Tocilizumab 8 mg/kg | Patient Assessment of of Pain (VAS) | Change at Week 12 | 41.7 mm | Standard Deviation 24.1 |
| Tocilizumab 8 mg/kg | Patient Assessment of of Pain (VAS) | Week 16 | 16.3 mm | Standard Deviation 17.7 |
| Tocilizumab 8 mg/kg | Patient Assessment of of Pain (VAS) | Change at Week 16 | 46.6 mm | Standard Deviation 24.5 |
| Tocilizumab 8 mg/kg | Patient Assessment of of Pain (VAS) | Week 20 | 10.6 mm | Standard Deviation 10.9 |
| Tocilizumab 8 mg/kg | Patient Assessment of of Pain (VAS) | Change at Week 20 | 52.3 mm | Standard Deviation 21.8 |
| Tocilizumab 8 mg/kg | Patient Assessment of of Pain (VAS) | Week 24 | 11.3 mm | Standard Deviation 14.3 |
| Tocilizumab 8 mg/kg | Patient Assessment of of Pain (VAS) | Change at Week 24 | 51.5 mm | Standard Deviation 25.4 |
Secondary
Patient Global Assessment of Disease Activity (VAS)
The participant's overall assessment of their current disease activity was displayed on a 100-mm horizontal VAS. The left-hand extreme (0 mm) of the line was described as no disease activity (symptom free and no arthritis symptoms) and the right-hand extreme (100 mm) was described as maximum disease activity (maximum arthritis disease activity). The change in Patient Global Assessment of Disease Activity was determined as the difference in values from baseline at each visit.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab 8 mg/kg | Patient Global Assessment of Disease Activity (VAS) | Change at Week 8 | 35.6 mm | Standard Deviation 22 |
| Tocilizumab 8 mg/kg | Patient Global Assessment of Disease Activity (VAS) | Baseline | 64.2 mm | Standard Deviation 18.6 |
| Tocilizumab 8 mg/kg | Patient Global Assessment of Disease Activity (VAS) | Week 4 | 40.6 mm | Standard Deviation 20.7 |
| Tocilizumab 8 mg/kg | Patient Global Assessment of Disease Activity (VAS) | Change at Week 4 | 23.6 mm | Standard Deviation 21.5 |
| Tocilizumab 8 mg/kg | Patient Global Assessment of Disease Activity (VAS) | Week 8 | 28.8 mm | Standard Deviation 19.8 |
| Tocilizumab 8 mg/kg | Patient Global Assessment of Disease Activity (VAS) | Week 12 | 21.4 mm | Standard Deviation 18.1 |
| Tocilizumab 8 mg/kg | Patient Global Assessment of Disease Activity (VAS) | Change at Week 12 | 42.8 mm | Standard Deviation 23.8 |
| Tocilizumab 8 mg/kg | Patient Global Assessment of Disease Activity (VAS) | Week 16 | 18.1 mm | Standard Deviation 19.2 |
| Tocilizumab 8 mg/kg | Patient Global Assessment of Disease Activity (VAS) | Change at Week 16 | 46.4 mm | Standard Deviation 25.2 |
| Tocilizumab 8 mg/kg | Patient Global Assessment of Disease Activity (VAS) | Week 20 | 11.3 mm | Standard Deviation 12.3 |
| Tocilizumab 8 mg/kg | Patient Global Assessment of Disease Activity (VAS) | Change at Week 20 | 53.0 mm | Standard Deviation 22 |
| Tocilizumab 8 mg/kg | Patient Global Assessment of Disease Activity (VAS) | Week 24 | 12.0 mm | Standard Deviation 15.3 |
| Tocilizumab 8 mg/kg | Patient Global Assessment of Disease Activity (VAS) | Change at Week 24 | 51.6 mm | Standard Deviation 25.3 |
Secondary
Percentage of Participants Achieving Remission (DAS28 <2.6)
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Participants with a DAS28 score \<2.6 were considered to have achieved remission.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab 8 mg/kg | Percentage of Participants Achieving Remission (DAS28 <2.6) | Week 24 (n=99) | 74.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants Achieving Remission (DAS28 <2.6) | Baseline (n=117) | 0.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants Achieving Remission (DAS28 <2.6) | Week 4 (n=116) | 16.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants Achieving Remission (DAS28 <2.6) | Week 8 (n=112) | 30.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants Achieving Remission (DAS28 <2.6) | Week 12 (n=109) | 48.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants Achieving Remission (DAS28 <2.6) | Week 16 (n=106) | 63.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants Achieving Remission (DAS28 <2.6) | Week 20 (n=103) | 73.8 percentage of participants |
Secondary
Percentage of Participants by DAS28 Response Category
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 ≤3.2 =low disease activity, DAS28 \>3.2 to ≤5.1=moderate to high disease activity; DAS28 \>5.1=high disease activity.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 ≤3.2, Baseline (n=117) | 0.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 ≤3.2, Week 4 (n=116) | 31.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 ≤3.2, Week 8 (n=112) | 50.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 ≤3.2, Week 12 (n=109) | 67.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 ≤3.2, Week 16 (n=106) | 81.1 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 ≤3.2, Week 20 (n=103) | 88.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 ≤3.2, Week 24 (n=99) | 83.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 >3.2 and ≤5.1, Baseline (n=117) | 25.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 >3.2 and ≤5.1, Week 4 (n=116) | 43.1 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 >3.2 and ≤5.1, Week 8 (n=112) | 40.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 >3.2 and ≤5.1, Week 12 (n=109) | 25.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 >3.2 and ≤5.1, Week 16 (n=106) | 13.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 >3.2 and ≤5.1, Week 20 (n=103) | 9.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 >3.2 and ≤5.1, Week 24 (n=99) | 13.1 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 >5.1, Baseline (n=117) | 73.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 >5.1, Week 4 (n=116) | 25.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 >5.1, Week 8 (n=112) | 8.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 >5.1, Week 12 (n=109) | 6.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 >5.1, Week 16 (n=106) | 5.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 >5.1, Week 20 (n=103) | 1.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants by DAS28 Response Category | DAS28 >5.1, Week 24 (n=99) | 3.0 percentage of participants |
Secondary
Percentage of Participants With a Clinically Meaningful Improvement in Disease Activity
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. A reduction in DAS28 of at least 1.2 units was considered a clinically meaningful improvement.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab 8 mg/kg | Percentage of Participants With a Clinically Meaningful Improvement in Disease Activity | Baseline | 0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Clinically Meaningful Improvement in Disease Activity | Week 4 | 76.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Clinically Meaningful Improvement in Disease Activity | Week 8 | 91.1 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Clinically Meaningful Improvement in Disease Activity | Week 12 | 91.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Clinically Meaningful Improvement in Disease Activity | Week 16 | 96.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Clinically Meaningful Improvement in Disease Activity | Week 20 | 98.1 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Clinically Meaningful Improvement in Disease Activity | Week 24 | 100 percentage of participants |
Secondary
Percentage of Participants With All-Cause Discontinuation of Tocilizumab by Study Visit
Percentage of participants discontinuing study treatment for any reason at every visit; causes of discontinuation in the summary included AEs, deaths, lost to follo-wup, AE and investigator decision and 'not determined'.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Population: All enrolled participants were included in the analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab 8 mg/kg | Percentage of Participants With All-Cause Discontinuation of Tocilizumab by Study Visit | Week 20 | 2.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With All-Cause Discontinuation of Tocilizumab by Study Visit | Week 4 | 3.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With All-Cause Discontinuation of Tocilizumab by Study Visit | Week 8 | 3.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With All-Cause Discontinuation of Tocilizumab by Study Visit | Week 12 | 2.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With All-Cause Discontinuation of Tocilizumab by Study Visit | Week 16 | 2.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With All-Cause Discontinuation of Tocilizumab by Study Visit | Week 24 | 3.3 percentage of participants |
Secondary
Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria
The ACR response rates ACR20, ACR50, ACR70 are defined as ≥20%, ≥50%, ≥70% improvement, respectively, in: swollen joint count (SJC) (66 joints) and tender joint count (TJC) (68 joints) and 3 of the following 5 assessments: Patient assessment of pain (VAS); Patient global assessment of disease activity (VAS); Investigator global assessment of disease activity (VAS); and acute phase response (ESR or CRP)
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR20, Week 4 (n=121) | 62.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR20, Week 8 (n=112) | 73.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR20, Week 12 (n=109) | 78.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR20, Week 16 (n=106) | 85.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR20, Week 20 (n=103) | 90.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR20, Week 24 (n=99) | 87.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR50, Week 4 (n=116) | 27.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR50, Week 8 (n=112) | 50.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR50, Week 12 (n=109) | 63.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR50, Week 16 (n=106) | 77.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR50, Week 20 (n=103) | 85.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR50, Week 24 (n=99) | 80.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR70, Week 4 (n=115) | 6.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR70, Week 8 (n=112) | 29.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR70, Week 12 (n=109) | 32.1 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR70, Week 16 (n=106) | 48.1 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR70, Week 20 (n=103) | 56.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria | ACR70, Week 24 (n=99) | 61.6 percentage of participants |
Secondary
Percentage of Participants With Lipid Elevations by Study Visit
Lipid panel assessed included TC, triglycerides, high-density lipoprotein (HDL), and LDL. Elevations were categorized as follows: LDL cholesterol: Optimal equals (=) less than (\<)100 mg/dL, Near optimal=100-129 mg/dL, Borderline high 130-159 mg/dL, High 160-189 mg/dL, Very High ≥190 mg/dL; Total cholesterol: Desirable \<200 mg/dL, Borderline high 200-239 mg/dL, High ≥240 mg/dL; HDL cholesterol: Low \<40 mg/dL, High ≥60 mg/dL; Triglycerides: Normal \<150 mg/dL, Borderline high 150-199 mg/dL, High 200-499 mg/dL, and Very high ≥500 mg/dL.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: Safety population; n (number) = number of participants assessed for the parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Optimal, Baseline (n=120) | 53.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Optimal, Week 4 (n=116) | 32.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Optimal, Week 8 (n=112) | 42.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Optimal, Week 12 (n=109) | 33.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Optimal, Week 16 (n=106) | 18.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Optimal, Week 20 (n=102) | 38.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Optimal, Week 24 (n=98) | 28.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Near Optimal, Baseline (n=120) | 30.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Near Optimal, Week 4 (n=116) | 31.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Near Optimal, Week 8 (n=112) | 22.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Near Optimal, Week 12 (n=109) | 25.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Near Optimal, Week 16 (n=106) | 17.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Near Optimal, Week 20 (n=102) | 22.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Near Optimal, Week 24 (n=98) | 27.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Borderline High, Baseline (n=120) | 12.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Borderline High, Week 4 (n=116) | 21.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Borderline High Week 8 (n=112) | 23.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Borderline High, Week 12 (n=109) | 20.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Borderline High, Week 16 (n=106) | 15.1 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Brderline High, Week 20 (n=102) | 25.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Borderline High, Week 24 (n=98) | 29.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: High, Baseline (n=120) | 2.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: High, Week 4 (n=116) | 7.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: High, Week 8 (n=112) | 9.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: High, Week 12 (n=109) | 14.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: High, Week 16 (n=106) | 9.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: High, Week 20 (n=102) | 10.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: High, Week 24 (n=98) | 9.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Very High, Baseline (n=120) | 0.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Very High, Week 4 (n=116) | 6.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Very High, Week 8 (n=112) | 1.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Very High, Week 12 (n=109) | 5.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Very High, Week 16 (n=106) | 38.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Very High, Week 20 (n=102) | 2.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | LDL Cholesterol: Very High, Week 24 (n=98) | 5.1 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: Desirable, Baseline (n=120) | 77.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: Desirable, Week 4 (n=116) | 58.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: Desirable, Week 8 (n=85) | 28.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: Desirable, Week 12 (n=109) | 56.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: Desirable, Week 16 (n=106) | 56.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: Desirable, Week 20 (n=103) | 52.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: Desirable, Week 24 (n=98) | 51.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: Borderline High, Baseline (n=120) | 18.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: Borderline High, Week 4 (n=116) | 25.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: Borderline High, Week 8 (n=85) | 28.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: Borderline High, Week 12 (n=109) | 23.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: Borderline High, Week 16 (n=106) | 26.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: Borderline High, Week 20 (n=103) | 28.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: Borderline High, Week 24 (n=98) | 26.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: High, Baseline (n=120) | 4.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: High, Week 4 (n=116) | 16.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: High, Week 8 (n=85) | 18.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: High, Week 12 (n=109) | 20.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: High, Week 16 (n=106) | 17.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: High, Week 20 (n=103) | 19.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | TC: High, Week 24 (n=98) | 22.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | HDL Cholesterol: Low, Baseline (n=49) | 28.1 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | HDL Cholesterol: Low, Week 4 (n=47) | 12.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | HDL Cholesterol: Low, Week 8 (n=54) | 17.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | HDL Cholesterol: Low, Week 12 (n=42) | 11.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | HDL Cholesterol: Low, Week 16 (n=51) | 24.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | HDL Cholesterol: Low, Week 20 (n=52) | 22.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | HDL Cholesterol: Low, Week 24 (n=48) | 19.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | HDL Cholesterol: High, Baseline (n=49) | 12.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | HDL Cholesterol: High, Week 4 (n=47) | 27.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | HDL Cholesterol: High, Week 8 (n=54) | 30.1 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | HDL Cholesterol: High, Week 12 (n=42) | 27.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | HDL Cholesterol: High, Week 16 (n=51) | 23.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | HDL Cholesterol: High, Week 20 (n=52) | 28.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | HDL Cholesterol: High, Week 24 (n=48) | 29.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Normal, Baseline (n=121) | 88.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Normal, Week 4 (n=116) | 40.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Normal, Week 8 (n=112) | 82.1 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Normal, Week 12 (n=109) | 80.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Normal, Week 16 (n=106) | 82.1 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Normal, Week 20 (n=103) | 75.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Normal, Week 24 (n=98) | 72.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Borderline High, Baseline (n=121) | 8.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Borderline High, Week 4 (n=116) | 28.4 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Borderline High, Week 8 (n=112) | 8.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Borderline High, Week 12 (n=109) | 8.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Borderline High, Week 16 (n=106) | 8.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Borderline High, Week 20 (n=103) | 9.7 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Borderline High, Week 24 (n=98) | 16.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: High, Baseline (n=121) | 3.3 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: High, Week 4 (n=116) | 25.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: High, Week 8 (n=112) | 9.8 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: High, Week 12 (n=109) | 11 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: High, Week 16 (n=106) | 8.5 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: High, Week 20 (n=103) | 14.6 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: High, Week 24 (n=98) | 11.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Very High, Baseline (n=121) | 0.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Very High, Week 4 (n=116) | 5.2 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Very High, Week 8 (n=112) | 0.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Very High, Week 12 (n=109) | 0.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Very High, Week 16 (n=106) | 0.9 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Very High, Week 20 (n=103) | 0.0 percentage of participants |
| Tocilizumab 8 mg/kg | Percentage of Participants With Lipid Elevations by Study Visit | Triglycerides: Very High, Week 24 (n=98) | 0.0 percentage of participants |
Secondary
Physician's Global Assessment of Disease Activity (VAS)
The physician's assessment of the participant's current disease activity was displayed on a 100-mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme (100 mm) was described as maximum disease activity. The Physician's Global Assessment of Disease Activity was completed by the Efficacy Assessor who could or could not be a physician. The change in Physician's Global Assessment of Disease Activity was determined as the difference in values from baseline at each visit.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab 8 mg/kg | Physician's Global Assessment of Disease Activity (VAS) | Baseline | 61.8 mm | Standard Deviation 18.3 |
| Tocilizumab 8 mg/kg | Physician's Global Assessment of Disease Activity (VAS) | Week 4 | 37.7 mm | Standard Deviation 20.5 |
| Tocilizumab 8 mg/kg | Physician's Global Assessment of Disease Activity (VAS) | Change at Week 4 | 24.3 mm | Standard Deviation 20.3 |
| Tocilizumab 8 mg/kg | Physician's Global Assessment of Disease Activity (VAS) | Week 8 | 26.7 mm | Standard Deviation 19.4 |
| Tocilizumab 8 mg/kg | Physician's Global Assessment of Disease Activity (VAS) | Change at Week 8 | 35.4 mm | Standard Deviation 21.7 |
| Tocilizumab 8 mg/kg | Physician's Global Assessment of Disease Activity (VAS) | Week 12 | 20.0 mm | Standard Deviation 17.3 |
| Tocilizumab 8 mg/kg | Physician's Global Assessment of Disease Activity (VAS) | Change at Week 12 | 41.6 mm | Standard Deviation 23.5 |
| Tocilizumab 8 mg/kg | Physician's Global Assessment of Disease Activity (VAS) | Week 16 | 16.0 mm | Standard Deviation 18.8 |
| Tocilizumab 8 mg/kg | Physician's Global Assessment of Disease Activity (VAS) | Change at Week 16 | 46.0 mm | Standard Deviation 24.6 |
| Tocilizumab 8 mg/kg | Physician's Global Assessment of Disease Activity (VAS) | Week 20 | 10.0 mm | Standard Deviation 10.9 |
| Tocilizumab 8 mg/kg | Physician's Global Assessment of Disease Activity (VAS) | Change at Week 20 | 51.8 mm | Standard Deviation 21 |
| Tocilizumab 8 mg/kg | Physician's Global Assessment of Disease Activity (VAS) | Week 24 | 10.7 mm | Standard Deviation 13.2 |
| Tocilizumab 8 mg/kg | Physician's Global Assessment of Disease Activity (VAS) | Change at Week 24 | 50.6 mm | Standard Deviation 23.3 |
Secondary
Swollen and Tender Joint Counts
The following 28 joints were assessed by the physician for swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). The following 28 joints were assessed by the physician for tenderness : metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). The change in SJC and TJC was determined as the difference in values from baseline at each visit.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | TJC Week 12 | 4.7 joints | Standard Deviation 5.8 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | SJC Baseline | 10.8 joints | Standard Deviation 7.4 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | SJC Week 4 | 4.8 joints | Standard Deviation 6 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | Change in SJC at Week 4 | 6.0 joints | Standard Deviation 6.5 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | SJC Week 8 | 3.1 joints | Standard Deviation 4.6 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | Change in SJC at Week 8 | 7.5 joints | Standard Deviation 6.8 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | SJC Week 12 | 2.8 joints | Standard Deviation 4.5 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | Change in SJC at Week 12 | 7.8 joints | Standard Deviation 6.9 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | SJC Week 16 | 1.8 joints | Standard Deviation 3.4 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | Change in SJC at Week 16 | 8.9 joints | Standard Deviation 7.4 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | SJC Week 20 | 0.9 joints | Standard Deviation 1.9 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | Change in SJC at Week 20 | 9.8 joints | Standard Deviation 7.4 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | SJC Week 24 | 1.0 joints | Standard Deviation 2.2 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | Change in SJC at Week 24 | 9.9 joints | Standard Deviation 7.6 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | TJC Baseline | 15.4 joints | Standard Deviation 8.8 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | TJC Week 4 | 9.3 joints | Standard Deviation 7.7 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | Change in TJC at Week 4 | 6.1 joints | Standard Deviation 7.6 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | TJC Week 8 | 6.2 joints | Standard Deviation 5.7 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | Change in TJC at Week 8 | 9.1 joints | Standard Deviation 7.2 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | Change in TJC at Week 12 | 10.4 joints | Standard Deviation 7.4 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | TJC Week 16 | 3.3 joints | Standard Deviation 4.5 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | Change in TJC at Week 16 | 12.0 joints | Standard Deviation 7.6 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | TJC Week 20 | 2.5 joints | Standard Deviation 3.5 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | Change in TJC at Week 20 | 12.7 joints | Standard Deviation 7.8 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | TJC Week 24 | 2.3 joints | Standard Deviation 4.1 |
| Tocilizumab 8 mg/kg | Swollen and Tender Joint Counts | Change in TJC at Week 24 | 13.0 joints | Standard Deviation 8.4 |
Secondary
Time to Achieve Clinically Meaningful Reduction in DAS28
A clinically meaningful improvement in DAS28 was defined as a reduction of at least 1.2 units. Time to achieving clinically meanigful improvement was calculated as the number of days from the first infusion to the first achievement of reduction of 1.2 units in DAS28.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab 8 mg/kg | Time to Achieve Clinically Meaningful Reduction in DAS28 | 44.7 days | Standard Deviation 29.1 |