Rheumatoid Arthritis
Conditions
Brief summary
This 2 part study will investigate the safety, tolerability and efficacy of MabT hera in combination with RoActemra in patients with active rheumatoid arthritis despite a stable dose of methotrexate. In Part 1 of the study, patients will be randomized to receive either MabThera 0.5g iv or placebo on days 1 and 15, follo wed by RoActemra at one of the ascending doses between 2mg/kg and 8mg/kg at week s 4, 8 and 12 (MabThera arm) or 8mg/kg (placebo arm). In Part 2, additional pati ents will be randomized to one of 2 groups to receive MabThera 0.5g on days 1 an d 15 followed by the selected dose (from Part 1)of RoActemra at weeks 4, 8 and 1 2, or placebo on days 1 and 15 followed by RoActemra 8mg/kg at weeks 4,8 and 12. All patients will then be eligible to receive extension treatment withRoActemra every 4 weeks. The anticipated time on study treatment is 12 months, and the tar get sample size is \<100 individuals.
Interventions
DRUGPlacebo
iv on days 1 and 15 (Parts 1 and 2)
DRUGrituximab [MabThera/Rituxan]
0.5g iv on days 1 and 15 (Parts 1 and 2)
DRUGtocilizumab [RoActemra/Actemra]
2mg/kg-8mg/kg iv in Part 1 and selected dose in Part 2, on weeks 4, 8 and 12---Arm 1\\n8mg/kg iv on weeks 4,8 and 12 (Parts 1 and 2)--- Arm 2
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* adult patients, 18-65 years of age; * rheumatoid arthritis, functional status I-III; * SJC\>=4 (28 joint count) and TJC\>=4 (28 joint count) at screening and baseline; * RF and/or anti-CCP positive; * may have failed up to 1 approved anti-TNF agent (infliximab, etanercept or adalimumab); * inadequate response to methotrexate, at a dose of 7.5-25mg weekly for at least 12 weeks, at a stable dose for past 4 weeks.
Exclusion criteria
* rheumatic autoimmune disease other than rheumatoid arthritis, or significant systemic involvement secondary to rheumatoid arthritis; * history of, or current, inflammatory joint disease other than rheumatoid arthritis; * diagnosis of juvenile idiopathic arthritis and/or rheumatoid arthritis before age 16; * significant cardiac or pulmonary disease; * previous treatment with any biologic agent for rheumatoid arthritis (other than infliximab, etanercept or adalimumab).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 16 | The Disease Activity Score based on 28 joint count (DAS28) and Erythrocyte Sedimentation Rate (ESR), is a measure of the participant's disease activity. It is based on the Tender Joint Count (TJC \[28 joints\]), Swollen Joint Count (SJC \[28 joints\]), participant's global assessment of disease activity (PtGA) Visual Analog Scale (VAS) in millimeters (mm), and ESR in millimeters per hour (mm/hour). DAS28-ESR scores range from 0 - 10. Definition of LDA was based on DAS28-ESR scores. To achieve LDA the DAS28-ESR had to be (less than or equal to) ≤ 3.2. DAS28-ESR equals (=) (0.56 times (\*) (square root)√ TJC plus (+) (0.28 \* √ SJC + (0.70 \* ln(ESR))+(0.014 \* (Global Health) GH) Where: TJC = based on 28 joints SJC = based on 28 joints ESR = erythrocyte sedimentation rate in mm/hour GH = participant's global assessment of disease activity ln = natural log |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 | Week 16 | DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline (greater than) \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or DAS28-ESR \>5.1 or change from baseline \>0.6 to ≤1.2 with DAS28 ≤5.1; nonresponders: change from baseline ≤0.6 or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1. |
| Change From Baseline in DAS28-ESR | Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48 | The DAS28-ESR score is a measure of the participant's disease activity. It is based on the TJC (28 joints), SJC (28 joints), participant's global assessment of disease activity (mm), and ESR (mm/hour). DAS28-ESR is expressed as a score on a scale with the minimum score=0 (best) to maximum score=10 (worst). DAS28-ESR scores were calculated as follows: DAS28-ESR = (0.56 \* √TJC)+(0.28 \* √SJC)+(0.70 \* ln(ESR))+(0.014 \* GH). No imputation used for tender and swollen joint counts, ESR, and patient's global assessment of disease activity VAS. |
| Clinical Disease Activity Index Scores | Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48 | The Clinical Disease Activity Index (CDAI) score was calculated according to the following formula: CDAI = SJC + TJC + GH/10 + EGA/10 Where: SJC = swollen joint count based on 28 joints; TJC = tender joint count based on 28 joints; GH = Participant's global assessment of disease activity; EGA = evaluator's (physician's) global assessment of disease activity. CDAI scores range from 0-76 and the following cut-off points for different disease activity states have been used: high disease activity \>22; moderate disease activity \>10 and ≤22; LDA \>2.8 and ≤10; and remission ≤ 2.8. No imputation used for TJC, SJC, Patient's Global Assessment of Disease Activity VAS and Physicians global assessment of disease activity VAS. |
| Simplified Disease Activity Index (SDAI) Scores | Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, and 48 | The SDAI is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), Participant and Physician assessed global disease activity (assessed on 0-100 mm VAS; higher scores = greater affection due to disease activity), and ESR (mm/hour). SDAI total score ranged from 0 to 86. Higher scores indicated greater disease activity. |
| Change From Baseline to Week 48 in SJC and TJC | Baseline and Week 48 | An assessment of 28 joints for swelling and tenderness will be made. Joints will be assessed and classified as swollen (1)/not swollen (0) and tender(1)/not tender (0) by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints were not taken into consideration for swelling or tenderness. The 28 joints assessed comprise shoulders (2 joints), elbows (2 joints), wrists (2 joints), metacarpophalangeal joints on digits 1-5 (10 joints), interphalangeal on digit 1 (2 joints), proximal interphalangeal joints on digits 2-5 (8 joints), and knees (2 joints). |
| Percentage of Participants Achieving Remission at Week 16 Assessed Using DAS28-ESR | Week 16 | The DAS28-ESR score is a measure of the participant's disease activity. It is based on the TJC (28 joints), SJC (28 joints), participant's global assessment of disease activity (mm), and ESR (mm/hour). DAS28-ESR is expressed on a unit on a scale with the minimum score=0 (best) to maximum score=10 (worst). Remission was defined as DAS28-ESR less than (\<) 2.6 |
| Change From Baseline to Week 48 in C-Reactive Protein (CRP) | Baseline and Week 48 | CRP is an acute phase reactant and is a measure of inflammation. |
| Change From Baseline to Week 48 in ESR | Baseline and Week 48 | ESR is an acute phase reactant and is a measure of inflammation. |
| Change From Baseline to Week 48 in Physician's Global Assessment of Disease Activity | Baseline and Week 48 | Physician Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm= maximum disease activity. The physician marked the line according to their assessment and the distance from the left edge was measured. |
| Change From Baseline to Week 48 in Participant's Global Assessment of Disease Activity | Baseline and Week 48 | Participant's Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm = maximum disease activity. The participant marked the line according to their assessment and the distance from the left edge was measured. |
| Change From Baseline to Week 48 in Participant's Assessment of Pain | Baseline and Week 48 | Participant's Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no pain and 100 mm = maximum pain. The participant marked the line according to their assessment and the distance from the left edge was measured. |
| Change From Baseline to Week 48 in Health Assessment Questionnaire (HAQ) | Baseline and Week 48 | The Stanford Health Assessment Questionnaire disability index specific for rheumatoid arthritis was completed by the participants for efficacy assessments. |
Countries
France, Germany, Greece, Netherlands, Poland, Spain, Switzerland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo + TCZ (8 mg/kg) Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | 3 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | 9 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Extended Safety Follow-Up | Withdrawal by Subject | 0 | 0 | 7 |
| Safety Follow-Up | Withdrawal by Subject | 1 | 0 | 0 |
| Treatment Period | Adverse Event | 0 | 2 | 0 |
| Treatment Period | Protocol Violation | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) | Total |
|---|---|---|---|---|
| Age, Continuous | 41.3 years STANDARD_DEVIATION 11.02 | 48.2 years STANDARD_DEVIATION 10.5 | 50.0 years STANDARD_DEVIATION 6.97 | 48.3 years STANDARD_DEVIATION 8.94 |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 9 / 9 | 11 / 12 |
| serious Total, serious adverse events | 1 / 3 | 2 / 9 | 3 / 12 |
Outcome results
Primary
Percentage of Participants Achieving Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR)
The Disease Activity Score based on 28 joint count (DAS28) and Erythrocyte Sedimentation Rate (ESR), is a measure of the participant's disease activity. It is based on the Tender Joint Count (TJC \[28 joints\]), Swollen Joint Count (SJC \[28 joints\]), participant's global assessment of disease activity (PtGA) Visual Analog Scale (VAS) in millimeters (mm), and ESR in millimeters per hour (mm/hour). DAS28-ESR scores range from 0 - 10. Definition of LDA was based on DAS28-ESR scores. To achieve LDA the DAS28-ESR had to be (less than or equal to) ≤ 3.2. DAS28-ESR equals (=) (0.56 times (\*) (square root)√ TJC plus (+) (0.28 \* √ SJC + (0.70 \* ln(ESR))+(0.014 \* (Global Health) GH) Where: TJC = based on 28 joints SJC = based on 28 joints ESR = erythrocyte sedimentation rate in mm/hour GH = participant's global assessment of disease activity ln = natural log
Time frame: Week 16
Population: Intent-to-Treat (ITT) Population: all randomized participants who received any part of an infusion of study medication. Last observation carried forward (LOCF) used for TJC and SJC, ESR and PtGA. If DAS28-ESR value was missing LDA was missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + TCZ (8 mg/kg) | Percentage of Participants Achieving Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) | 50.0 percentage of participants |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Percentage of Participants Achieving Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) | 11.1 percentage of participants |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Percentage of Participants Achieving Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) | 20.0 percentage of participants |
Secondary
Change From Baseline in DAS28-ESR
The DAS28-ESR score is a measure of the participant's disease activity. It is based on the TJC (28 joints), SJC (28 joints), participant's global assessment of disease activity (mm), and ESR (mm/hour). DAS28-ESR is expressed as a score on a scale with the minimum score=0 (best) to maximum score=10 (worst). DAS28-ESR scores were calculated as follows: DAS28-ESR = (0.56 \* √TJC)+(0.28 \* √SJC)+(0.70 \* ln(ESR))+(0.014 \* GH). No imputation used for tender and swollen joint counts, ESR, and patient's global assessment of disease activity VAS.
Time frame: Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48
Population: ITT Population; number (n) = number of participants analyzed at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + TCZ (8 mg/kg) | Change From Baseline in DAS28-ESR | Week 16 (n=4,9,9) | -3.0 units on a scale | Standard Deviation 0.8 |
| Placebo + TCZ (8 mg/kg) | Change From Baseline in DAS28-ESR | Week 48 (n=4,8,7) | -3.3 units on a scale | Standard Deviation 1.84 |
| Placebo + TCZ (8 mg/kg) | Change From Baseline in DAS28-ESR | Week 24 (n=4,9,8) | -3.5 units on a scale | Standard Deviation 1.28 |
| Placebo + TCZ (8 mg/kg) | Change From Baseline in DAS28-ESR | Week 20 (n=4,9,9) | -3.6 units on a scale | Standard Deviation 0.7 |
| Placebo + TCZ (8 mg/kg) | Change From Baseline in DAS28-ESR | Week 4 (n=4,9,10) | -1.9 units on a scale | Standard Deviation 1.73 |
| Placebo + TCZ (8 mg/kg) | Change From Baseline in DAS28-ESR | Week 40 (n=3,8,8) | -2.6 units on a scale | Standard Deviation 1.24 |
| Placebo + TCZ (8 mg/kg) | Change From Baseline in DAS28-ESR | Week 12 (n=4,10,9) | -2.7 units on a scale | Standard Deviation 0.57 |
| Placebo + TCZ (8 mg/kg) | Change From Baseline in DAS28-ESR | Week 8 (n=4,10,10) | -2.7 units on a scale | Standard Deviation 0.55 |
| Placebo + TCZ (8 mg/kg) | Change From Baseline in DAS28-ESR | Week 32 (n=4,9,8) | -2.6 units on a scale | Standard Deviation 1.62 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Change From Baseline in DAS28-ESR | Week 20 (n=4,9,9) | -2.2 units on a scale | Standard Deviation 1.16 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Change From Baseline in DAS28-ESR | Week 4 (n=4,9,10) | -0.7 units on a scale | Standard Deviation 1.44 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Change From Baseline in DAS28-ESR | Week 8 (n=4,10,10) | -0.5 units on a scale | Standard Deviation 1.33 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Change From Baseline in DAS28-ESR | Week 12 (n=4,10,9) | -1.2 units on a scale | Standard Deviation 1.6 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Change From Baseline in DAS28-ESR | Week 16 (n=4,9,9) | -1.8 units on a scale | Standard Deviation 1.44 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Change From Baseline in DAS28-ESR | Week 24 (n=4,9,8) | -2.2 units on a scale | Standard Deviation 1.14 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Change From Baseline in DAS28-ESR | Week 32 (n=4,9,8) | -3.1 units on a scale | Standard Deviation 1.92 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Change From Baseline in DAS28-ESR | Week 40 (n=3,8,8) | -2.2 units on a scale | Standard Deviation 1.63 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Change From Baseline in DAS28-ESR | Week 48 (n=4,8,7) | -2.9 units on a scale | Standard Deviation 1.5 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Change From Baseline in DAS28-ESR | Week 12 (n=4,10,9) | -2.3 units on a scale | Standard Deviation 1.36 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Change From Baseline in DAS28-ESR | Week 4 (n=4,9,10) | -1.0 units on a scale | Standard Deviation 0.72 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Change From Baseline in DAS28-ESR | Week 32 (n=4,9,8) | -3.3 units on a scale | Standard Deviation 1.83 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Change From Baseline in DAS28-ESR | Week 8 (n=4,10,10) | -1.9 units on a scale | Standard Deviation 1.31 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Change From Baseline in DAS28-ESR | Week 48 (n=4,8,7) | -3.0 units on a scale | Standard Deviation 1.24 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Change From Baseline in DAS28-ESR | Week 20 (n=4,9,9) | -2.7 units on a scale | Standard Deviation 1.45 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Change From Baseline in DAS28-ESR | Week 16 (n=4,9,9) | -2.3 units on a scale | Standard Deviation 1.25 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Change From Baseline in DAS28-ESR | Week 40 (n=3,8,8) | -2.7 units on a scale | Standard Deviation 1.02 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Change From Baseline in DAS28-ESR | Week 24 (n=4,9,8) | -2.9 units on a scale | Standard Deviation 1.34 |
Secondary
Change From Baseline to Week 48 in C-Reactive Protein (CRP)
CRP is an acute phase reactant and is a measure of inflammation.
Time frame: Baseline and Week 48
Population: Data were not collected because the study was terminated early.
Secondary
Change From Baseline to Week 48 in ESR
ESR is an acute phase reactant and is a measure of inflammation.
Time frame: Baseline and Week 48
Population: Data were not collected because the study was terminated early.
Secondary
Change From Baseline to Week 48 in Health Assessment Questionnaire (HAQ)
The Stanford Health Assessment Questionnaire disability index specific for rheumatoid arthritis was completed by the participants for efficacy assessments.
Time frame: Baseline and Week 48
Population: Data were not collected because the study was terminated early.
Secondary
Change From Baseline to Week 48 in Participant's Assessment of Pain
Participant's Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no pain and 100 mm = maximum pain. The participant marked the line according to their assessment and the distance from the left edge was measured.
Time frame: Baseline and Week 48
Population: Data were not collected because the study was terminated early.
Secondary
Change From Baseline to Week 48 in Participant's Global Assessment of Disease Activity
Participant's Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm = maximum disease activity. The participant marked the line according to their assessment and the distance from the left edge was measured.
Time frame: Baseline and Week 48
Population: Data were not collected because the study was terminated early.
Secondary
Change From Baseline to Week 48 in Physician's Global Assessment of Disease Activity
Physician Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm= maximum disease activity. The physician marked the line according to their assessment and the distance from the left edge was measured.
Time frame: Baseline and Week 48
Population: Data were not collected because the study was terminated early.
Secondary
Change From Baseline to Week 48 in SJC and TJC
An assessment of 28 joints for swelling and tenderness will be made. Joints will be assessed and classified as swollen (1)/not swollen (0) and tender(1)/not tender (0) by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints were not taken into consideration for swelling or tenderness. The 28 joints assessed comprise shoulders (2 joints), elbows (2 joints), wrists (2 joints), metacarpophalangeal joints on digits 1-5 (10 joints), interphalangeal on digit 1 (2 joints), proximal interphalangeal joints on digits 2-5 (8 joints), and knees (2 joints).
Time frame: Baseline and Week 48
Population: Data were not collected because the study was terminated early.
Secondary
Clinical Disease Activity Index Scores
The Clinical Disease Activity Index (CDAI) score was calculated according to the following formula: CDAI = SJC + TJC + GH/10 + EGA/10 Where: SJC = swollen joint count based on 28 joints; TJC = tender joint count based on 28 joints; GH = Participant's global assessment of disease activity; EGA = evaluator's (physician's) global assessment of disease activity. CDAI scores range from 0-76 and the following cut-off points for different disease activity states have been used: high disease activity \>22; moderate disease activity \>10 and ≤22; LDA \>2.8 and ≤10; and remission ≤ 2.8. No imputation used for TJC, SJC, Patient's Global Assessment of Disease Activity VAS and Physicians global assessment of disease activity VAS.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48
Population: ITT Population; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + TCZ (8 mg/kg) | Clinical Disease Activity Index Scores | Week 4 (n=4, 8, 10) | 21.2 units on a scale | Standard Deviation 14.19 |
| Placebo + TCZ (8 mg/kg) | Clinical Disease Activity Index Scores | Week 24 (n=4, 9, 8) | 9.2 units on a scale | Standard Deviation 6.71 |
| Placebo + TCZ (8 mg/kg) | Clinical Disease Activity Index Scores | Week 16 (n=4,10, 9) | 9.5 units on a scale | Standard Deviation 5.7 |
| Placebo + TCZ (8 mg/kg) | Clinical Disease Activity Index Scores | Baseline (n=4, 10, 10) | 37.7 units on a scale | Standard Deviation 4.59 |
| Placebo + TCZ (8 mg/kg) | Clinical Disease Activity Index Scores | Week 20 (n=4, 8, 9) | 10.8 units on a scale | Standard Deviation 4.46 |
| Placebo + TCZ (8 mg/kg) | Clinical Disease Activity Index Scores | Week 40 (n=3, 8, 8) | 20.3 units on a scale | Standard Deviation 8.35 |
| Placebo + TCZ (8 mg/kg) | Clinical Disease Activity Index Scores | Week 8 (n=4,10,10) | 14.6 units on a scale | Standard Deviation 4.38 |
| Placebo + TCZ (8 mg/kg) | Clinical Disease Activity Index Scores | Week 48 (n=4, 7, 8) | 11.6 units on a scale | Standard Deviation 10.11 |
| Placebo + TCZ (8 mg/kg) | Clinical Disease Activity Index Scores | Week 32 (n=4, 9, 8) | 15.2 units on a scale | Standard Deviation 10.42 |
| Placebo + TCZ (8 mg/kg) | Clinical Disease Activity Index Scores | Week 12 (n=4,10, 9) | 16.3 units on a scale | Standard Deviation 10.52 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Clinical Disease Activity Index Scores | Baseline (n=4, 10, 10) | 36.4 units on a scale | Standard Deviation 9.16 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Clinical Disease Activity Index Scores | Week 4 (n=4, 8, 10) | 23.4 units on a scale | Standard Deviation 12.38 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Clinical Disease Activity Index Scores | Week 8 (n=4,10,10) | 29.4 units on a scale | Standard Deviation 14.91 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Clinical Disease Activity Index Scores | Week 12 (n=4,10, 9) | 23.2 units on a scale | Standard Deviation 12.47 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Clinical Disease Activity Index Scores | Week 16 (n=4,10, 9) | 19.5 units on a scale | Standard Deviation 15.42 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Clinical Disease Activity Index Scores | Week 20 (n=4, 8, 9) | 15.4 units on a scale | Standard Deviation 7.76 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Clinical Disease Activity Index Scores | Week 24 (n=4, 9, 8) | 12.6 units on a scale | Standard Deviation 3.98 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Clinical Disease Activity Index Scores | Week 32 (n=4, 9, 8) | 11.5 units on a scale | Standard Deviation 13.14 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Clinical Disease Activity Index Scores | Week 40 (n=3, 8, 8) | 17.9 units on a scale | Standard Deviation 16.4 |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Clinical Disease Activity Index Scores | Week 48 (n=4, 7, 8) | 12.8 units on a scale | Standard Deviation 12.15 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Clinical Disease Activity Index Scores | Week 24 (n=4, 9, 8) | 10.9 units on a scale | Standard Deviation 5.47 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Clinical Disease Activity Index Scores | Week 8 (n=4,10,10) | 15.5 units on a scale | Standard Deviation 9.96 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Clinical Disease Activity Index Scores | Baseline (n=4, 10, 10) | 33.0 units on a scale | Standard Deviation 7.69 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Clinical Disease Activity Index Scores | Week 32 (n=4, 9, 8) | 9.3 units on a scale | Standard Deviation 9.42 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Clinical Disease Activity Index Scores | Week 4 (n=4, 8, 10) | 20.0 units on a scale | Standard Deviation 6.97 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Clinical Disease Activity Index Scores | Week 16 (n=4,10, 9) | 12.7 units on a scale | Standard Deviation 8.32 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Clinical Disease Activity Index Scores | Week 48 (n=4, 7, 8) | 7.1 units on a scale | Standard Deviation 6.41 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Clinical Disease Activity Index Scores | Week 20 (n=4, 8, 9) | 11.6 units on a scale | Standard Deviation 6.64 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Clinical Disease Activity Index Scores | Week 12 (n=4,10, 9) | 13.4 units on a scale | Standard Deviation 8.4 |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Clinical Disease Activity Index Scores | Week 40 (n=3, 8, 8) | 11.8 units on a scale | Standard Deviation 5.31 |
Secondary
Percentage of Participants Achieving Remission at Week 16 Assessed Using DAS28-ESR
The DAS28-ESR score is a measure of the participant's disease activity. It is based on the TJC (28 joints), SJC (28 joints), participant's global assessment of disease activity (mm), and ESR (mm/hour). DAS28-ESR is expressed on a unit on a scale with the minimum score=0 (best) to maximum score=10 (worst). Remission was defined as DAS28-ESR less than (\<) 2.6
Time frame: Week 16
Population: ITT Population; LOCF used for TJC, ESR, and PtGA. If the DAS28-ESR value was missing then remission or LDA was missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + TCZ (8 mg/kg) | Percentage of Participants Achieving Remission at Week 16 Assessed Using DAS28-ESR | 0.0 percentage of participants |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Percentage of Participants Achieving Remission at Week 16 Assessed Using DAS28-ESR | 0.0 percentage of participants |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Percentage of Participants Achieving Remission at Week 16 Assessed Using DAS28-ESR | 10.0 percentage of participants |
Secondary
Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16
DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline (greater than) \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or DAS28-ESR \>5.1 or change from baseline \>0.6 to ≤1.2 with DAS28 ≤5.1; nonresponders: change from baseline ≤0.6 or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1.
Time frame: Week 16
Population: ITT Population; No imputation used for TJC, SJC, ESR, and PtGA. EULAR response was set to missing when the DAS28 score was missing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + TCZ (8 mg/kg) | Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 | Moderate Response | 50.0 percentage of participants |
| Placebo + TCZ (8 mg/kg) | Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 | No Response | 0.0 percentage of participants |
| Placebo + TCZ (8 mg/kg) | Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 | Good Response | 50.0 percentage of participants |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 | Moderate Response | 66.7 percentage of participants |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 | No Response | 22.2 percentage of participants |
| Rituximab (0.5 g) + TCZ (2 mg/kg) | Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 | Good Response | 11.1 percentage of participants |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 | No Response | 11.1 percentage of participants |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 | Good Response | 22.2 percentage of participants |
| Rituximab (0.5 g) + TCZ (4 mg/kg) | Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 | Moderate Response | 66.7 percentage of participants |
Secondary
Simplified Disease Activity Index (SDAI) Scores
The SDAI is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), Participant and Physician assessed global disease activity (assessed on 0-100 mm VAS; higher scores = greater affection due to disease activity), and ESR (mm/hour). SDAI total score ranged from 0 to 86. Higher scores indicated greater disease activity.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, and 48
Population: Data were not collected because the study was terminated early.