Rheumatoid Arthritis
Conditions
Brief summary
This study will compare the efficacy and safety of re-treatment with 2 doses of MabThera (rituximab) in patients with active rheumatoid arthritis (RA) who have previously experienced an inadequate response or intolerance to anti-tumor necrosis factor (anti-TNF) therapies etanercept, infliximab or adalimumab therapy. All patients will receive infusions of 1000 mg intravenous (IV) MabThera on Days 1 and 15; at Week 24 patients who have demonstrated a moderate or good response will be randomized to receive re-treatment with either 1 or 2 additional infusions of 1000 mg IV MabThera. The anticipated time on study treatment is 2+ years, and the target sample size is 100-500 individuals.
Interventions
DRUGrituximab
Arm A: 1000 mg IV (one infusion) every 2 months \\nArm B: 2 x 1000 mg IV (2 infusions) every 2 months
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients \>18 years of age * RA for \>=6 months * Receiving outpatient treatment * Ongoing treatment with methotrexate for \>=3 months, stable for \>=1 month * Inadequate response or intolerance to etanercept, infliximab or adalimumab
Exclusion criteria
* Previous treatment with MabThera * Concurrent treatment with any anti TNF-alfa therapy or biologic therapy * Previous treatment with any investigational cell-depleting therapies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (DAS28-CRP) Area Under the Curve (AUC) at Week 104 | Week 104 | DAS28-CRP was based on joint counts, overall participant assessment, and serum CRP levels (measured in milligrams per liter \[mg/L\]) at each visit. Joint counts included swollen joint count (SJC) and tender joint count (TJC). Total score range was 0 to 9.4; a higher score indicated more disease activity. DAS28-CRP less than or equal to (≤)3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity, and less than (\<)2.6 equals (=) remission. The AUC of all DAS28-CRP values between Day 1 and Week 104 (15 values of protocol visits) was calculated using the trapeze method (AUC between t1 and t2=(t2-t1)\*((DAS28-CRP at t1 + DAS28-CRP at t2)/2). The true visit dates were used to calculate the time between 2 DAS28-CRP evaluations. All the AUC were censored at Week 104 (linear extrapolation using the 2 last DAS28-CRP values (Weeks 96 and 104) to obtain the true DAS28-CRP value at the true Week 104). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DAS28-CRP During the Initial Treatment | Days 1 and 15, and Weeks 6, 12, and 24 | Mean DAS28-CRP at Week 24 of the Initial Treatment study. DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity, and \<2.6=remission. |
| DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | Day 1, 24 weeks following each infusion up to 72 Weeks | DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity, and \<2.6=remission. |
| Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) | Week 24 of the Initial Treatment, 24 weeks after first retreatment, and 24 weeks after second retreatment | Percentage of participants with clinical remission and low disease activity as measured by DAS28-CRP for Arm A and Arm B at Week 24 of the Initial Treatment, at 24 weeks after first re-treatment, and at 24 weeks after second retreatment. DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity and \<2.6 = remission. |
| DAS28-CRP AUC Weighted Time | Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 | DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity, and \<2.6=remission. |
| Time to Achieve DAS28-CRP Remission After the First Course | Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 | DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP \<2.6=remission. |
| Time to Achieve DAS28-CRP Remission After Retreatment | Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 | DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP \<2.6=remission. |
| Time to Achieve DAS28-CRP ≤3.2 After Retreatment | Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 | DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity. |
| Duration of DAS28-CRP Remission After the First Course of Treatment | Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 | DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP \<2.6=remission. |
| Duration of DAS28-CRP Remission After Retreatment | Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 | DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP \<2.6=remission. |
| Duration of DAS28-CRP ≤3.2 After the First Course of Treatment | Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 | DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity. |
| Duration of DAS28-CRP ≤3.2 After Retreatment | Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 | DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity. |
| Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | Week 24 of the initial treatment, 24 weeks after first retreatment, and 24 weeks after second retreatment | ACR20/50/70 response defined as ≥20%, 50%, or 70% improvement, respectively, in TJC and SJC, and ≥20%, 50%, or 70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: Patient Global Assessment of Pain, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity (on a visual analog scale \[VAS\]); Health Assessment Questionnaire-Disability Index (HAQ-DI); and CRP. |
| Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Day 15, Weeks 6, 12, and 24 | DAS28-based EULAR response criteria were used to measure individual response as no response, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders = change from baseline \>1.2 with a DAS28 score of ≤3.2; moderate responders = change from baseline \>1.2 with a DAS28 score of \>3.2 to ≤ 5.1 or change from baseline \>0.6 to ≤1.2 with a DAS28 score of ≤5.1; non-responders = change from baseline ≤0.6 or change from baseline \>0.6 and ≤ 1.2 with a DAS28 score of \>5.1. |
| Percentage of Participants Achieving a Response During Retreatment by EULAR Category | Week 24, 24 weeks after 1st retreatment, 24 weeks after 2nd retreatment | DAS28-based EULAR response criteria were used to measure individual response as no response, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders = change from baseline \>1.2 with a DAS28 score of ≤3.2; moderate responders = change from baseline \>1.2 with a DAS28 score of \>3.2 to ≤ 5.1 or change from baseline \>0.6 to ≤1.2 with a DAS28 score of ≤5.1; non-responders = change from baseline ≤0.6 or change from baseline \>0.6 and ≤ 1.2 with a DAS28 score of \>5.1. |
| Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment | Week 24 of the initial treatment, 24 weeks after first re-treatment, and 24 weeks after second retreatment | RF is the auto antibody directed against immunoglobulin G (IgG) and its concentration is observed in human serum or plasma. RF value higher than 20 international units per milliliter (IU/mL) is considered positive. |
| Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment | Week 24 of the initial treatment, 24 weeks after first re-treatment, and 24 weeks after second retreatment | Anti-CCP antibodies are auto antibodies (antibodies directed against 1 or more of an individual's own proteins) that are frequently detected in the blood of rheumatoid arthritis participants. Anti-CCP antibodies value higher than 10 U/mL is considered positive. |
| Physician's Global Assessment of Disease Activity | Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment | The Physician's Global Assessment of disease activity is assessed on a 0 to 100 millimeter (mm) horizontal VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as maximum disease activity (maximum arthritis disease activity). Physicians were asked to mark the line and the distance from the left edge was measured. Higher values correspond to worst state of participant (high disease activity). |
| Patient Global Assessment of Disease Activity | Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment | The Patient's Global Assessment of Disease Activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as maximum disease activity (maximum arthritis disease activity). Higher values correspond to worst state of participant (high disease activity). |
| Patient's Global Assessment of Pain | Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment | The participants assessed their pain over the past 24 hours on a 0 to 100 mm horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm as unbearable pain. Participants were asked to mark the line and the distance from the left edge was measured. Higher values correspond to worst state of participant (high pain levels). |
| Time to Achieve DAS28-CRP ≤3.2 After the First Course of Treatment | Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 | DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity. |
| Cortisone Intake AUC (Time- and Weight-Weighted) | Day 1 (each infusion), Week 24, Week 104 | All cortisone intakes (in mg) were taken into account (oral, IV \[including the cortisone administration before the rituximab infusion\], intramuscular, and intra-articular). |
| Total Mean Dose of Cortisone Between Week 24 and Week 104 | Week 24 to Week 104 | All cortisone intakes were taken into account, including oral, IV (including the cortisone administration before the rituximab infusion), intramuscular and intra-articular. |
| HAQ-DI Scores | Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0=least difficulty and 3 extreme difficulty. |
| Short Form 12 (SF-12) Physical Health Composite Score | Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment | Physical and Mental Health Composite Scores of SF-12 were computed using the scores of 12 questions and range from 0 to 100, where a 0 score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. |
| SF-12 Mental Health Composite Score | Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment | Mental Health Composite Scores of SF-12 were computed using the scores of 12 questions and range from 0 to 100, where a 0 score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. |
| Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index | Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment | The MOS Sleep Scale measures most constructs of sleep. The scale has a battery of questions to measure specific aspects of sleep in participants with co-morbidities. The SLP6 index is comprised of 6 items: provides a summary of sleep problems and contains questions from the sleep disturbance, sleep adequacy, respiratory impairment, and somnolence domains. The SLP6 index score ranges between 0 and 100, with higher values corresponding to more sleep problems. |
| Percentage of Participants Reporting Acceptable Disease Activity Symptom State Assessed Using Patient Acceptable and Unacceptable Symptom State (PASS) | Week 24, 12 and 24 weeks after 1st retreatment | Percentage of participants reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of disease activity they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of disease activity they had during the last 48 hours. In the case of missing data, participants who withdrew from the study because of inefficacy or toxicity were considered unacceptable. |
| Patient Global Assessment of Disease Activity in Participants Reporting Acceptable Symptoms Using PASS | Week 24, 12 and 24 weeks after 1st retreatment | The Patient's Global Assessment of Disease Activity assessed in participants reporting acceptable symptom state using PASS (acceptance to remain for the rest of their lives with the level of disease activity they had during the last 48 hours) on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as maximum disease activity (maximum arthritis disease activity). Higher values correspond to worst state of participant (high disease activity). |
| Percentage of Participants With Minimum Clinically Important Improvement (MCII) in Disease Activity | Week 24, 12 and 24 weeks after 1st retreatment | Participants were asked how their disease activity had been during the last 48 hours compared to baseline. Those participants that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse-more disease activity. |
| Change From Baseline in Patient Global Assessment of Disease Activity in Participants With MCII | Baseline, Week 24, 12 and 24 weeks after 1st retreatment | The Patient's Global Assessment of Disease Activity was assessed in participants reporting MCII on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as maximum disease activity (maximum arthritis disease activity). Higher values correspond to worst state of participant (high disease activity). |
| Percentage of Participants Reporting Acceptable Symptom State in Functioning Assessed Using PASS | Week 24, 12 and 24 weeks after 1st retreatment | Percentage of participants reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of function they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of function they had during the last 48 hours. In the case of missing data, participants who withdrew from the study because of inefficacy or toxicity were considered unacceptable. |
| HAQ-DI Scores in Participants Reporting Acceptable Function Using PASS | Week 24, 12 and 24 weeks after 1st retreatment | HAQ-DI was assessed in participants reporting acceptable symptom state using PASS (acceptance to remain for the rest of their lives with the level of disease activity they had during the last 48 hours). HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0=least difficulty and 3 extreme difficulty. |
| Percentage of Participants With MCII in Functioning | Week 24, 12 and 24 weeks after 1st retreatment | Participants were asked how their functioning had been during the last 48 hours compared to baseline. Those participants that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse. |
| Change From Baseline in HAQ-DI in Participants With MCII | Baseline, Week 24, 12 and 24 weeks after 1st retreatment | HAQ-DI was assessed in participants with MCII. HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0=least difficulty and 3 extreme difficulty. |
| Percentage of Participants With Acceptable Symptom State in Pain Assessed Using PASS | Week 24, 12 and 24 weeks after 1st retreatment | Percentage of participants reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of pain they had during the last 48 hours. In the case of missing data, participants who withdrew from the study because of inefficacy or toxicity were considered unacceptable. |
| Patient Global Assessment of Pain in Participants Reporting Acceptable Symptoms Using PASS | Week 24, 12 and 24 weeks after 1st retreatment | Patient Global Assessment of Pain assessed in participants reporting acceptable symptom state using PASS (acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours) on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm as unbearable pain. Higher values correspond to worst state of participant (high pain levels). |
| Percentage of Participants With MCII in Pain | Week 24, 12 and 24 weeks after 1st retreatment | Participants were asked how their pain had been during the last 48 hours compared to baseline. Those participants that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse pain. |
| Change From Baseline in Patient Global Assessment of Pain in Participants With MCII | Baseline, Week 24, 12 and 24 weeks after 1st retreatment | The participants assessed their pain over the past 24 hours on a 0 to 100 mm horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm as unbearable pain. Participants were asked to mark the line and the distance from the left edge was measured. Higher values correspond to worst state of participant (high pain levels). |
| Participant Assessment of Fatigue | Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment | Participants were asked to rate their level of fatigue over the last 7 days on a 100-mm VAS. The left-hand extreme of the line equals 0 mm, and is described as no fatigue and the right-hand extreme equals 100 mm as extreme fatigue. Participants were asked to mark the line and the distance from the left edge was measured. Higher values correspond to worst state of participant (high levels of fatigue). |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Randomized Retreatment Arm A: Rituximab 1000 mg Participants received rituximab 1000 mg IV on Days 1 and 15. After Week 24, if DAS28 was \>3.2, participants received one additional infusion of rituximab 1000 mg IV. Participants received methylprednisolone 100 mg IV 30 minutes before each rituximab infusion and MTX ≥10 mg/week by mouth or parenteral throughout course of treatment. | 70 |
| Randomized Retreatment Arm B: Rituximab 1000 mg x 2 Participants received rituximab 1000 mg IV on Days 1 and 15. After Week 24, if DAS28 was \>3.2, participants received two additional infusions of rituximab 1000 mg IV, 15 days apart. Participants received methylprednisolone 100 mg IV 30 minutes before each rituximab infusion and ≥10 mg/week MTX by mouth or parenteral throughout course of treatment. | 73 |
| Nonrandomized: Rituximab 1000 mg Participants received rituximab 1000 mg IV on Days 1 and 15, methylprednisolone 100 mg IV at 30 minutes before each rituximab infusion, and MTX ≥10 mg/week by mouth or parenterally throughout treatment course. | 81 |
| Total | 224 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative reason or other | 1 | 1 | 2 |
| Overall Study | Adverse Event | 0 | 2 | 4 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 6 | 1 | 11 |
| Overall Study | Lost to Follow-up | 1 | 2 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 5 | 6 |
Baseline characteristics
| Characteristic | Total | Randomized Retreatment Arm A: Rituximab 1000 mg | Randomized Retreatment Arm B: Rituximab 1000 mg x 2 | Nonrandomized: Rituximab 1000 mg |
|---|---|---|---|---|
| Age, Continuous | 56.0 years STANDARD_DEVIATION 11 | 54.5 years STANDARD_DEVIATION 11.5 | 57.2 years STANDARD_DEVIATION 10.4 | 56.1 years STANDARD_DEVIATION 11.2 |
| Sex: Female, Male Female | 187 Participants | 55 Participants | 62 Participants | 70 Participants |
| Sex: Female, Male Male | 37 Participants | 15 Participants | 11 Participants | 11 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 | 61 / 66 | 65 / 68 | 72 / 81 |
| serious Total, serious adverse events | 19 / 66 | 25 / 68 | 16 / 81 |
Outcome results
Primary
Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (DAS28-CRP) Area Under the Curve (AUC) at Week 104
DAS28-CRP was based on joint counts, overall participant assessment, and serum CRP levels (measured in milligrams per liter \[mg/L\]) at each visit. Joint counts included swollen joint count (SJC) and tender joint count (TJC). Total score range was 0 to 9.4; a higher score indicated more disease activity. DAS28-CRP less than or equal to (≤)3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity, and less than (\<)2.6 equals (=) remission. The AUC of all DAS28-CRP values between Day 1 and Week 104 (15 values of protocol visits) was calculated using the trapeze method (AUC between t1 and t2=(t2-t1)\*((DAS28-CRP at t1 + DAS28-CRP at t2)/2). The true visit dates were used to calculate the time between 2 DAS28-CRP evaluations. All the AUC were censored at Week 104 (linear extrapolation using the 2 last DAS28-CRP values (Weeks 96 and 104) to obtain the true DAS28-CRP value at the true Week 104).
Time frame: Week 104
Population: Per Protocol (PP) population: all randomized participants in the Intent-to-Treat (ITT) population (defined as all randomized participants) without major protocol violations. Participants were grouped according to their initially assigned treatment arm irrespective of the treatment actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Group | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (DAS28-CRP) Area Under the Curve (AUC) at Week 104 | 2761.4 score on a scale*week | Standard Error 507.8 |
| Nonrandomized Group | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (DAS28-CRP) Area Under the Curve (AUC) at Week 104 | 2666.0 score on a scale*week | Standard Error 490.4 |
95% CI: [-131.22, 233.98]
Secondary
Change From Baseline in HAQ-DI in Participants With MCII
HAQ-DI was assessed in participants with MCII. HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0=least difficulty and 3 extreme difficulty.
Time frame: Baseline, Week 24, 12 and 24 weeks after 1st retreatment
Population: ITT population; only participants with MCII were included in the analysis. n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | Change From Baseline in HAQ-DI in Participants With MCII | Week 24 (n=47,52) | -0.11 units on a scale | Standard Deviation 0.46 |
| Randomized Group | Change From Baseline in HAQ-DI in Participants With MCII | 1st retreatment, Week 12 (n=38,30) | -0.03 units on a scale | Standard Deviation 0.3 |
| Randomized Group | Change From Baseline in HAQ-DI in Participants With MCII | 1st retreatment, Week 24 (n=38,30) | -0.07 units on a scale | Standard Deviation 0.24 |
| Nonrandomized Group | Change From Baseline in HAQ-DI in Participants With MCII | Week 24 (n=47,52) | -0.06 units on a scale | Standard Deviation 0.56 |
| Nonrandomized Group | Change From Baseline in HAQ-DI in Participants With MCII | 1st retreatment, Week 12 (n=38,30) | -0.11 units on a scale | Standard Deviation 0.39 |
| Nonrandomized Group | Change From Baseline in HAQ-DI in Participants With MCII | 1st retreatment, Week 24 (n=38,30) | -0.09 units on a scale | Standard Deviation 0.29 |
Secondary
Change From Baseline in Patient Global Assessment of Disease Activity in Participants With MCII
The Patient's Global Assessment of Disease Activity was assessed in participants reporting MCII on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as maximum disease activity (maximum arthritis disease activity). Higher values correspond to worst state of participant (high disease activity).
Time frame: Baseline, Week 24, 12 and 24 weeks after 1st retreatment
Population: ITT population; only participants with MCII were included in the analysis. n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | Change From Baseline in Patient Global Assessment of Disease Activity in Participants With MCII | Week 24 (n=49,56) | -12.4 mm | Standard Deviation 20.7 |
| Randomized Group | Change From Baseline in Patient Global Assessment of Disease Activity in Participants With MCII | 1st retreatment, Week 12 (n=38,30) | -4.2 mm | Standard Deviation 16 |
| Randomized Group | Change From Baseline in Patient Global Assessment of Disease Activity in Participants With MCII | 1st retreatment, Week 24 (n=40,37) | -2.5 mm | Standard Deviation 17.8 |
| Nonrandomized Group | Change From Baseline in Patient Global Assessment of Disease Activity in Participants With MCII | Week 24 (n=49,56) | -4.6 mm | Standard Deviation 22.9 |
| Nonrandomized Group | Change From Baseline in Patient Global Assessment of Disease Activity in Participants With MCII | 1st retreatment, Week 12 (n=38,30) | -9.2 mm | Standard Deviation 17.7 |
| Nonrandomized Group | Change From Baseline in Patient Global Assessment of Disease Activity in Participants With MCII | 1st retreatment, Week 24 (n=40,37) | -2.9 mm | Standard Deviation 20.6 |
Secondary
Change From Baseline in Patient Global Assessment of Pain in Participants With MCII
The participants assessed their pain over the past 24 hours on a 0 to 100 mm horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm as unbearable pain. Participants were asked to mark the line and the distance from the left edge was measured. Higher values correspond to worst state of participant (high pain levels).
Time frame: Baseline, Week 24, 12 and 24 weeks after 1st retreatment
Population: ITT population; only participants with MCII were included in the analysis. n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | Change From Baseline in Patient Global Assessment of Pain in Participants With MCII | Week 24 (n=48,56) | -13.5 mm | Standard Deviation 21 |
| Randomized Group | Change From Baseline in Patient Global Assessment of Pain in Participants With MCII | 1st retreatment, Week 12 (n=39,35) | -2.7 mm | Standard Deviation 13.6 |
| Randomized Group | Change From Baseline in Patient Global Assessment of Pain in Participants With MCII | 1st retreatment, Week 24 (n=42,35) | -3.5 mm | Standard Deviation 24.3 |
| Nonrandomized Group | Change From Baseline in Patient Global Assessment of Pain in Participants With MCII | Week 24 (n=48,56) | -4.3 mm | Standard Deviation 23.9 |
| Nonrandomized Group | Change From Baseline in Patient Global Assessment of Pain in Participants With MCII | 1st retreatment, Week 12 (n=39,35) | -8.9 mm | Standard Deviation 16.4 |
| Nonrandomized Group | Change From Baseline in Patient Global Assessment of Pain in Participants With MCII | 1st retreatment, Week 24 (n=42,35) | -3.2 mm | Standard Deviation 18.4 |
Secondary
Cortisone Intake AUC (Time- and Weight-Weighted)
All cortisone intakes (in mg) were taken into account (oral, IV \[including the cortisone administration before the rituximab infusion\], intramuscular, and intra-articular).
Time frame: Day 1 (each infusion), Week 24, Week 104
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | Cortisone Intake AUC (Time- and Weight-Weighted) | Day 1 to Week 104 (n=69,73) | 0.08 mg*week | Standard Error 0.06 |
| Randomized Group | Cortisone Intake AUC (Time- and Weight-Weighted) | 1st retreatment to Week 104 (n=65,68) | 0.08 mg*week | Standard Error 0.06 |
| Randomized Group | Cortisone Intake AUC (Time- and Weight-Weighted) | Week 24 to Week 104 (n=69,73) | 0.08 mg*week | Standard Error 0.06 |
| Nonrandomized Group | Cortisone Intake AUC (Time- and Weight-Weighted) | Day 1 to Week 104 (n=69,73) | 0.09 mg*week | Standard Error 0.06 |
| Nonrandomized Group | Cortisone Intake AUC (Time- and Weight-Weighted) | 1st retreatment to Week 104 (n=65,68) | 0.09 mg*week | Standard Error 0.06 |
| Nonrandomized Group | Cortisone Intake AUC (Time- and Weight-Weighted) | Week 24 to Week 104 (n=69,73) | 0.09 mg*week | Standard Error 0.06 |
Comparison: Day 1 to Week 104p-value: 0.389Wilcoxon (Mann-Whitney)
Comparison: 1st retreatment to Week 104p-value: 0.374Wilcoxon (Mann-Whitney)
Comparison: Weel 24 to Week 104p-value: 0.277Wilcoxon (Mann-Whitney)
Secondary
DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course
DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity, and \<2.6=remission.
Time frame: Day 1, 24 weeks following each infusion up to 72 Weeks
Population: ITT Population; number (n)=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | Initial treatment, Week 24 (n=70,73) | 3.57 units on a scale | Standard Deviation 0.89 |
| Randomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | 1st retreatment, Change at Week 24 (n=66,68) | -0.67 units on a scale | Standard Deviation 1.15 |
| Randomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | 1st retreatment, Day 1 (n=66,68) | 4.33 units on a scale | Standard Deviation 0.91 |
| Randomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | 2nd retreatment, Day 1 (n=49,48) | 4.60 units on a scale | Standard Deviation 0.87 |
| Randomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | Change at Week 24 (n=70,73) | -2.22 units on a scale | Standard Deviation 0.96 |
| Randomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | 2nd retreatment, Week 24 (n=41,39) | 3.72 units on a scale | Standard Deviation 1.1 |
| Randomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | 1st retreatment, Week 24 (n=66,68) | 3.67 units on a scale | Standard Deviation 1.15 |
| Randomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | 2nd retreatment, Change at Week 24 (n=41,39) | -0.94 units on a scale | Standard Deviation 1.17 |
| Randomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | Initial treatment, Day 1 (n=70,73) | 5.79 units on a scale | Standard Deviation 0.85 |
| Nonrandomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | 2nd retreatment, Change at Week 24 (n=41,39) | -0.78 units on a scale | Standard Deviation 1.07 |
| Nonrandomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | Initial treatment, Day 1 (n=70,73) | 5.84 units on a scale | Standard Deviation 0.86 |
| Nonrandomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | Initial treatment, Week 24 (n=70,73) | 3.73 units on a scale | Standard Deviation 0.8 |
| Nonrandomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | Change at Week 24 (n=70,73) | -2.11 units on a scale | Standard Deviation 0.93 |
| Nonrandomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | 1st retreatment, Day 1 (n=66,68) | 4.45 units on a scale | Standard Deviation 0.8 |
| Nonrandomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | 1st retreatment, Week 24 (n=66,68) | 3.69 units on a scale | Standard Deviation 1.05 |
| Nonrandomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | 1st retreatment, Change at Week 24 (n=66,68) | -0.79 units on a scale | Standard Deviation 1.13 |
| Nonrandomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | 2nd retreatment, Day 1 (n=49,48) | 4.55 units on a scale | Standard Deviation 0.96 |
| Nonrandomized Group | DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course | 2nd retreatment, Week 24 (n=41,39) | 3.76 units on a scale | Standard Deviation 1.12 |
Comparison: Change from Day 1 to Week 24 (initial treatment)p-value: 0.465Wilcoxon (Mann-Whitney)
Comparison: Arm A vs. Arm B: Change from 1st retreatment to 24 weeks afterp-value: 0.161Wilcoxon (Mann-Whitney)
Comparison: Arm A vs. Arm B: Change from 2nd retreatment to 24 weeks afterp-value: 0.524Student t-test
Secondary
DAS28-CRP AUC Weighted Time
DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity, and \<2.6=remission.
Time frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Group | DAS28-CRP AUC Weighted Time | 3.82 units on a scale*week | Standard Deviation 0.71 |
| Nonrandomized Group | DAS28-CRP AUC Weighted Time | 3.88 units on a scale*week | Standard Deviation 0.71 |
Secondary
DAS28-CRP During the Initial Treatment
Mean DAS28-CRP at Week 24 of the Initial Treatment study. DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity, and \<2.6=remission.
Time frame: Days 1 and 15, and Weeks 6, 12, and 24
Population: Overall population: all participants with at least one treatment intake.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | DAS28-CRP During the Initial Treatment | First Course, Day 15 | 5.33 units on a scale | Standard Deviation 1.09 |
| Randomized Group | DAS28-CRP During the Initial Treatment | Follow-up, Week 12 | 4.13 units on a scale | Standard Deviation 0.91 |
| Randomized Group | DAS28-CRP During the Initial Treatment | Follow-up, Week 6 | 4.69 units on a scale | Standard Deviation 0.95 |
| Randomized Group | DAS28-CRP During the Initial Treatment | Follow-up, Week 24 | 3.65 units on a scale | Standard Deviation 0.85 |
| Randomized Group | DAS28-CRP During the Initial Treatment | First Course, Day 1 | 5.82 units on a scale | Standard Deviation 0.85 |
| Nonrandomized Group | DAS28-CRP During the Initial Treatment | Follow-up, Week 24 | 5.24 units on a scale | Standard Deviation 1.08 |
| Nonrandomized Group | DAS28-CRP During the Initial Treatment | First Course, Day 1 | 5.77 units on a scale | Standard Deviation 0.9 |
| Nonrandomized Group | DAS28-CRP During the Initial Treatment | First Course, Day 15 | 5.42 units on a scale | Standard Deviation 1.07 |
| Nonrandomized Group | DAS28-CRP During the Initial Treatment | Follow-up, Week 6 | 5.12 units on a scale | Standard Deviation 1.05 |
| Nonrandomized Group | DAS28-CRP During the Initial Treatment | Follow-up, Week 12 | 5.00 units on a scale | Standard Deviation 1.19 |
Secondary
Duration of DAS28-CRP ≤3.2 After Retreatment
DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity.
Time frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
Population: ITT population; only participants with a response (DAS28-CRP ≤3.2) during retreatment (at any point) were included in the analysis. n=number of participants assessed at a given visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Randomized Group | Duration of DAS28-CRP ≤3.2 After Retreatment | 1st retreatment (n=35,40) | 27.0 weeks |
| Randomized Group | Duration of DAS28-CRP ≤3.2 After Retreatment | 2nd retreatment (n=29,23) | 10.1 weeks |
| Nonrandomized Group | Duration of DAS28-CRP ≤3.2 After Retreatment | 1st retreatment (n=35,40) | 17.0 weeks |
| Nonrandomized Group | Duration of DAS28-CRP ≤3.2 After Retreatment | 2nd retreatment (n=29,23) | 16.0 weeks |
Secondary
Duration of DAS28-CRP ≤3.2 After the First Course of Treatment
DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity.
Time frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
Population: ITT population; only participants with a response (DAS28-CRP ≤3.2) during first course of treatment (at any point) were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized Group | Duration of DAS28-CRP ≤3.2 After the First Course of Treatment | 14.3 weeks |
Secondary
Duration of DAS28-CRP Remission After Retreatment
DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP \<2.6=remission.
Time frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
Population: ITT population; only participants with a response (DAS28-CRP \<2.6) during retreatment (at any point) were included in the analysis. n=number of participants assessed at a given visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Randomized Group | Duration of DAS28-CRP Remission After Retreatment | 1st retreatment (n=21,22) | 16.0 weeks |
| Randomized Group | Duration of DAS28-CRP Remission After Retreatment | 2nd retreatment (n=17,11) | 9.0 weeks |
| Nonrandomized Group | Duration of DAS28-CRP Remission After Retreatment | 1st retreatment (n=21,22) | 8.0 weeks |
| Nonrandomized Group | Duration of DAS28-CRP Remission After Retreatment | 2nd retreatment (n=17,11) | 8.0 weeks |
Secondary
Duration of DAS28-CRP Remission After the First Course of Treatment
DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP \<2.6=remission.
Time frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
Population: ITT population; only participants with a response (DAS28-CRP \<2.6) during initial treatment (at any point) were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized Group | Duration of DAS28-CRP Remission After the First Course of Treatment | 11.7 weeks |
Secondary
HAQ-DI Scores
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0=least difficulty and 3 extreme difficulty.
Time frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | HAQ-DI Scores | Before 1st retreatment (n=64,67) | 1.26 units on a scale | Standard Deviation 0.67 |
| Randomized Group | HAQ-DI Scores | 1st retreatment, Day 1 (n=58,58) | 1.32 units on a scale | Standard Deviation 0.68 |
| Randomized Group | HAQ-DI Scores | 1st retreatment, Week 12 (n=62,61) | 1.31 units on a scale | Standard Deviation 0.66 |
| Randomized Group | HAQ-DI Scores | Initial treatment, Week 24 (n=68,72) | 1.25 units on a scale | Standard Deviation 0.67 |
| Randomized Group | HAQ-DI Scores | 1st retreatment, Week 24 (n=63,59) | 1.26 units on a scale | Standard Deviation 0.72 |
| Randomized Group | HAQ-DI Scores | Initial treatment, Day 1 (n=70,69) | 1.74 units on a scale | Standard Deviation 0.61 |
| Nonrandomized Group | HAQ-DI Scores | 1st retreatment, Week 24 (n=63,59) | 1.32 units on a scale | Standard Deviation 0.72 |
| Nonrandomized Group | HAQ-DI Scores | Initial treatment, Day 1 (n=70,69) | 1.75 units on a scale | Standard Deviation 0.69 |
| Nonrandomized Group | HAQ-DI Scores | Initial treatment, Week 24 (n=68,72) | 1.31 units on a scale | Standard Deviation 0.74 |
| Nonrandomized Group | HAQ-DI Scores | 1st retreatment, Day 1 (n=58,58) | 1.42 units on a scale | Standard Deviation 0.73 |
| Nonrandomized Group | HAQ-DI Scores | 1st retreatment, Week 12 (n=62,61) | 1.33 units on a scale | Standard Deviation 0.72 |
| Nonrandomized Group | HAQ-DI Scores | Before 1st retreatment (n=64,67) | 1.35 units on a scale | Standard Deviation 0.73 |
Secondary
HAQ-DI Scores in Participants Reporting Acceptable Function Using PASS
HAQ-DI was assessed in participants reporting acceptable symptom state using PASS (acceptance to remain for the rest of their lives with the level of disease activity they had during the last 48 hours). HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0=least difficulty and 3 extreme difficulty.
Time frame: Week 24, 12 and 24 weeks after 1st retreatment
Population: ITT population; only participants with 'acceptable' symptom state assessed using PASS were included in the analysis. n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | HAQ-DI Scores in Participants Reporting Acceptable Function Using PASS | Week 24 (n=46,48) | 1.16 units on a scale | Standard Deviation 0.69 |
| Randomized Group | HAQ-DI Scores in Participants Reporting Acceptable Function Using PASS | 1st retreatment, Week 12 (n=44,33) | 1.20 units on a scale | Standard Deviation 0.7 |
| Randomized Group | HAQ-DI Scores in Participants Reporting Acceptable Function Using PASS | 1st retreatment, Week 24 (n=40,36) | 1.14 units on a scale | Standard Deviation 0.75 |
| Nonrandomized Group | HAQ-DI Scores in Participants Reporting Acceptable Function Using PASS | Week 24 (n=46,48) | 1.16 units on a scale | Standard Deviation 0.74 |
| Nonrandomized Group | HAQ-DI Scores in Participants Reporting Acceptable Function Using PASS | 1st retreatment, Week 12 (n=44,33) | 1.08 units on a scale | Standard Deviation 0.71 |
| Nonrandomized Group | HAQ-DI Scores in Participants Reporting Acceptable Function Using PASS | 1st retreatment, Week 24 (n=40,36) | 1.08 units on a scale | Standard Deviation 0.72 |
Secondary
Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index
The MOS Sleep Scale measures most constructs of sleep. The scale has a battery of questions to measure specific aspects of sleep in participants with co-morbidities. The SLP6 index is comprised of 6 items: provides a summary of sleep problems and contains questions from the sleep disturbance, sleep adequacy, respiratory impairment, and somnolence domains. The SLP6 index score ranges between 0 and 100, with higher values corresponding to more sleep problems.
Time frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
Population: ITT population;n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index | Initial treatment, Day 1 (n=68,66) | 52.15 units on a scale | Standard Deviation 15.32 |
| Randomized Group | Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index | Initial treatment, Week 24 (n=65,70) | 43.73 units on a scale | Standard Deviation 14.9 |
| Randomized Group | Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index | Before 1st retreatment (n=62,65) | 45.44 units on a scale | Standard Deviation 13.97 |
| Randomized Group | Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index | 1st retreatment, Day 1 (n=57,56) | 46.25 units on a scale | Standard Deviation 16.53 |
| Randomized Group | Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index | 1st retreatment, Week 12 (n=61,59) | 43.64 units on a scale | Standard Deviation 14.41 |
| Randomized Group | Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index | 1st retreatment, Week 24 (n=63,59) | 44.74 units on a scale | Standard Deviation 15.35 |
| Nonrandomized Group | Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index | 1st retreatment, Week 12 (n=61,59) | 43.74 units on a scale | Standard Deviation 18.6 |
| Nonrandomized Group | Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index | Initial treatment, Day 1 (n=68,66) | 49.89 units on a scale | Standard Deviation 15.81 |
| Nonrandomized Group | Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index | 1st retreatment, Day 1 (n=57,56) | 44.94 units on a scale | Standard Deviation 16.02 |
| Nonrandomized Group | Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index | Initial treatment, Week 24 (n=65,70) | 40.50 units on a scale | Standard Deviation 17.17 |
| Nonrandomized Group | Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index | 1st retreatment, Week 24 (n=63,59) | 40.08 units on a scale | Standard Deviation 16.76 |
| Nonrandomized Group | Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index | Before 1st retreatment (n=62,65) | 41.27 units on a scale | Standard Deviation 17.01 |
Secondary
Participant Assessment of Fatigue
Participants were asked to rate their level of fatigue over the last 7 days on a 100-mm VAS. The left-hand extreme of the line equals 0 mm, and is described as no fatigue and the right-hand extreme equals 100 mm as extreme fatigue. Participants were asked to mark the line and the distance from the left edge was measured. Higher values correspond to worst state of participant (high levels of fatigue).
Time frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | Participant Assessment of Fatigue | Initial Treatment, Week 24 (n=70,73) | 37.1 mm | Standard Deviation 24.2 |
| Randomized Group | Participant Assessment of Fatigue | 1st retreatment, Day 1 (n=65,64) | 50.6 mm | Standard Deviation 22.6 |
| Randomized Group | Participant Assessment of Fatigue | Initial Treatment, Day 1 (n=70,73) | 62.1 mm | Standard Deviation 21.4 |
| Randomized Group | Participant Assessment of Fatigue | 1st retreatment, Week 12 (n=63,65) | 45.2 mm | Standard Deviation 23 |
| Randomized Group | Participant Assessment of Fatigue | Before 1st retreatment (n=64,66) | 44.5 mm | Standard Deviation 20.8 |
| Randomized Group | Participant Assessment of Fatigue | 1st retreatment, Week 24 (n=64,60) | 43.0 mm | Standard Deviation 25.3 |
| Nonrandomized Group | Participant Assessment of Fatigue | 1st retreatment, Week 24 (n=64,60) | 38.9 mm | Standard Deviation 23.6 |
| Nonrandomized Group | Participant Assessment of Fatigue | Initial Treatment, Day 1 (n=70,73) | 62.0 mm | Standard Deviation 22.5 |
| Nonrandomized Group | Participant Assessment of Fatigue | Initial Treatment, Week 24 (n=70,73) | 39.8 mm | Standard Deviation 25.8 |
| Nonrandomized Group | Participant Assessment of Fatigue | Before 1st retreatment (n=64,66) | 41.2 mm | Standard Deviation 26.1 |
| Nonrandomized Group | Participant Assessment of Fatigue | 1st retreatment, Day 1 (n=65,64) | 51.7 mm | Standard Deviation 21.6 |
| Nonrandomized Group | Participant Assessment of Fatigue | 1st retreatment, Week 12 (n=63,65) | 45.3 mm | Standard Deviation 25.5 |
Secondary
Patient Global Assessment of Disease Activity
The Patient's Global Assessment of Disease Activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as maximum disease activity (maximum arthritis disease activity). Higher values correspond to worst state of participant (high disease activity).
Time frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | Patient Global Assessment of Disease Activity | Initial treatment, Day 1 (n=70,73) | 63.0 mm | Standard Deviation 20.4 |
| Randomized Group | Patient Global Assessment of Disease Activity | Initial treatment, Week 24 (n=70,73) | 29.9 mm | Standard Deviation 22.3 |
| Randomized Group | Patient Global Assessment of Disease Activity | Before 1st retreatment (n=65,67) | 33.2 mm | Standard Deviation 19.6 |
| Randomized Group | Patient Global Assessment of Disease Activity | 1st retreatment, Day 1 (n=65,66) | 43.7 mm | Standard Deviation 21.2 |
| Randomized Group | Patient Global Assessment of Disease Activity | 1st retreatment, Week 12 (n=63,65) | 34.8 mm | Standard Deviation 21.2 |
| Randomized Group | Patient Global Assessment of Disease Activity | 1st retreatment, Week 24 (n=64,60) | 35.1 mm | Standard Deviation 24.6 |
| Nonrandomized Group | Patient Global Assessment of Disease Activity | 1st retreatment, Week 12 (n=63,65) | 34.5 mm | Standard Deviation 25.3 |
| Nonrandomized Group | Patient Global Assessment of Disease Activity | Initial treatment, Day 1 (n=70,73) | 64.2 mm | Standard Deviation 18 |
| Nonrandomized Group | Patient Global Assessment of Disease Activity | 1st retreatment, Day 1 (n=65,66) | 46.6 mm | Standard Deviation 21.3 |
| Nonrandomized Group | Patient Global Assessment of Disease Activity | Initial treatment, Week 24 (n=70,73) | 32.6 mm | Standard Deviation 22.7 |
| Nonrandomized Group | Patient Global Assessment of Disease Activity | 1st retreatment, Week 24 (n=64,60) | 34.1 mm | Standard Deviation 23.1 |
| Nonrandomized Group | Patient Global Assessment of Disease Activity | Before 1st retreatment (n=65,67) | 34.7 mm | Standard Deviation 22.3 |
Secondary
Patient Global Assessment of Disease Activity in Participants Reporting Acceptable Symptoms Using PASS
The Patient's Global Assessment of Disease Activity assessed in participants reporting acceptable symptom state using PASS (acceptance to remain for the rest of their lives with the level of disease activity they had during the last 48 hours) on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as maximum disease activity (maximum arthritis disease activity). Higher values correspond to worst state of participant (high disease activity).
Time frame: Week 24, 12 and 24 weeks after 1st retreatment
Population: ITT population; only participants with 'acceptable' symptom state assessed using PASS were included in the analysis. n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | Patient Global Assessment of Disease Activity in Participants Reporting Acceptable Symptoms Using PASS | Week 24 (n=47,52) | 23.4 mm | Standard Deviation 18.5 |
| Randomized Group | Patient Global Assessment of Disease Activity in Participants Reporting Acceptable Symptoms Using PASS | 1st retreatment, Week 12 (n=44,35) | 27.4 mm | Standard Deviation 16.6 |
| Randomized Group | Patient Global Assessment of Disease Activity in Participants Reporting Acceptable Symptoms Using PASS | 1st retreatment, Week 24 (n=43,36) | 26.3 mm | Standard Deviation 19.5 |
| Nonrandomized Group | Patient Global Assessment of Disease Activity in Participants Reporting Acceptable Symptoms Using PASS | Week 24 (n=47,52) | 28.4 mm | Standard Deviation 19.1 |
| Nonrandomized Group | Patient Global Assessment of Disease Activity in Participants Reporting Acceptable Symptoms Using PASS | 1st retreatment, Week 12 (n=44,35) | 27.3 mm | Standard Deviation 21.8 |
| Nonrandomized Group | Patient Global Assessment of Disease Activity in Participants Reporting Acceptable Symptoms Using PASS | 1st retreatment, Week 24 (n=43,36) | 25.7 mm | Standard Deviation 16.4 |
Secondary
Patient Global Assessment of Pain in Participants Reporting Acceptable Symptoms Using PASS
Patient Global Assessment of Pain assessed in participants reporting acceptable symptom state using PASS (acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours) on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm as unbearable pain. Higher values correspond to worst state of participant (high pain levels).
Time frame: Week 24, 12 and 24 weeks after 1st retreatment
Population: ITT population; only participants with 'acceptable' symptom state assessed using PASS were included in the analysis. n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | Patient Global Assessment of Pain in Participants Reporting Acceptable Symptoms Using PASS | Week 24 (n=46,51) | 21.5 mm | Standard Deviation 16.2 |
| Randomized Group | Patient Global Assessment of Pain in Participants Reporting Acceptable Symptoms Using PASS | 1st retreatment, Week 12 (n=40,34) | 26.8 mm | Standard Deviation 17.3 |
| Randomized Group | Patient Global Assessment of Pain in Participants Reporting Acceptable Symptoms Using PASS | 1st retreatment, Week 24 (n=43,35) | 26.3 mm | Standard Deviation 20.1 |
| Nonrandomized Group | Patient Global Assessment of Pain in Participants Reporting Acceptable Symptoms Using PASS | 1st retreatment, Week 12 (n=40,34) | 27.6 mm | Standard Deviation 22.4 |
| Nonrandomized Group | Patient Global Assessment of Pain in Participants Reporting Acceptable Symptoms Using PASS | Week 24 (n=46,51) | 26.4 mm | Standard Deviation 18.5 |
| Nonrandomized Group | Patient Global Assessment of Pain in Participants Reporting Acceptable Symptoms Using PASS | 1st retreatment, Week 24 (n=43,35) | 25.1 mm | Standard Deviation 17.3 |
Secondary
Patient's Global Assessment of Pain
The participants assessed their pain over the past 24 hours on a 0 to 100 mm horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm as unbearable pain. Participants were asked to mark the line and the distance from the left edge was measured. Higher values correspond to worst state of participant (high pain levels).
Time frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | Patient's Global Assessment of Pain | Initial Treatment, Day 1 (n=70,73) | 61.9 mm | Standard Deviation 22.3 |
| Randomized Group | Patient's Global Assessment of Pain | Initial Treatment, Week 24 (n=70,73) | 28.5 mm | Standard Deviation 22 |
| Randomized Group | Patient's Global Assessment of Pain | Before 1st retreatment (n=65,67) | 34.4 mm | Standard Deviation 21.3 |
| Randomized Group | Patient's Global Assessment of Pain | 1st re-treatment, Day 1 (n=65,67) | 41.1 mm | Standard Deviation 21.5 |
| Randomized Group | Patient's Global Assessment of Pain | 1st retreatment, Week 12 (n=64,60) | 34.3 mm | Standard Deviation 21.4 |
| Randomized Group | Patient's Global Assessment of Pain | 1st retreatment, Week 24 (n=64,60) | 34.4 mm | Standard Deviation 24.6 |
| Nonrandomized Group | Patient's Global Assessment of Pain | 1st retreatment, Week 12 (n=64,60) | 33.9 mm | Standard Deviation 25.6 |
| Nonrandomized Group | Patient's Global Assessment of Pain | Initial Treatment, Day 1 (n=70,73) | 60.1 mm | Standard Deviation 19.9 |
| Nonrandomized Group | Patient's Global Assessment of Pain | 1st re-treatment, Day 1 (n=65,67) | 45.2 mm | Standard Deviation 22.4 |
| Nonrandomized Group | Patient's Global Assessment of Pain | Initial Treatment, Week 24 (n=70,73) | 30.0 mm | Standard Deviation 21.7 |
| Nonrandomized Group | Patient's Global Assessment of Pain | 1st retreatment, Week 24 (n=64,60) | 34.3 mm | Standard Deviation 23.7 |
| Nonrandomized Group | Patient's Global Assessment of Pain | Before 1st retreatment (n=65,67) | 32.9 mm | Standard Deviation 23 |
Secondary
Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70)
ACR20/50/70 response defined as ≥20%, 50%, or 70% improvement, respectively, in TJC and SJC, and ≥20%, 50%, or 70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: Patient Global Assessment of Pain, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity (on a visual analog scale \[VAS\]); Health Assessment Questionnaire-Disability Index (HAQ-DI); and CRP.
Time frame: Week 24 of the initial treatment, 24 weeks after first retreatment, and 24 weeks after second retreatment
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR20: 1st Retreatment, Week 24 | 63.6 percentage of participants |
| Randomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR50: 2nd Retreatment, Week 24 | 32.6 percentage of participants |
| Randomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR50: Initial Treatment, Week 24 | 35.7 percentage of participants |
| Randomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR70: Initial Treatment, Week 24 | 12.9 percentage of participants |
| Randomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR20: 2nd Retreatment, Week 24 | 65.1 percentage of participants |
| Randomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR70: 1st Retreatment, Week 24 | 16.7 percentage of participants |
| Randomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR50: 1st Retreatment, Week 24 | 33.3 percentage of participants |
| Randomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR70: 2nd Retreatment, Week 24 | 18.6 percentage of participants |
| Randomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR20: Initial Treatment, Week 24 | 78.6 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR70: 2nd Retreatment, Week 24 | 20.0 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR20: Initial Treatment, Week 24 | 75.3 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR20: 1st Retreatment, Week 24 | 61.2 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR20: 2nd Retreatment, Week 24 | 60.0 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR50: Initial Treatment, Week 24 | 32.9 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR50: 1st Retreatment, Week 24 | 32.8 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR50: 2nd Retreatment, Week 24 | 42.5 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR70: Initial Treatment, Week 24 | 11.0 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) | ACR70: 1st Retreatment, Week 24 | 19.4 percentage of participants |
Secondary
Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category
DAS28-based EULAR response criteria were used to measure individual response as no response, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders = change from baseline \>1.2 with a DAS28 score of ≤3.2; moderate responders = change from baseline \>1.2 with a DAS28 score of \>3.2 to ≤ 5.1 or change from baseline \>0.6 to ≤1.2 with a DAS28 score of ≤5.1; non-responders = change from baseline ≤0.6 or change from baseline \>0.6 and ≤ 1.2 with a DAS28 score of \>5.1.
Time frame: Day 15, Weeks 6, 12, and 24
Population: Overall population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | No response: Week 6 | 36 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | No response: Week 12 | 11 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | No response: Week 24 | 3 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Good response: Day 15 | 4 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Good response: Week 6 | 5 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Good response: Week 12 | 15 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Good response: Week 24 | 32 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Moderate response: Day 15 | 22 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Moderate response: Week 6 | 59 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Moderate response: Week 12 | 73 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Moderate response: Week 24 | 66 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | No response: Day 15 | 74 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Moderate response: Week 24 | 15 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | No response: Week 6 | 67 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Good response: Week 24 | 3 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | No response: Week 12 | 61 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Moderate response: Week 12 | 35 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | No response: Week 24 | 82 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Moderate response: Day 15 | 20 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Good response: Day 15 | 3 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | No response: Day 15 | 78 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Good response: Week 6 | 4 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Moderate response: Week 6 | 29 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category | Good response: Week 12 | 4 percentage of participants |
Secondary
Percentage of Participants Achieving a Response During Retreatment by EULAR Category
DAS28-based EULAR response criteria were used to measure individual response as no response, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders = change from baseline \>1.2 with a DAS28 score of ≤3.2; moderate responders = change from baseline \>1.2 with a DAS28 score of \>3.2 to ≤ 5.1 or change from baseline \>0.6 to ≤1.2 with a DAS28 score of ≤5.1; non-responders = change from baseline ≤0.6 or change from baseline \>0.6 and ≤ 1.2 with a DAS28 score of \>5.1.
Time frame: Week 24, 24 weeks after 1st retreatment, 24 weeks after 2nd retreatment
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | Good response: 1st retreatment (n=66,67) | 35 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | Moderate response: 2nd retreatment (n=43,40) | 54 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | Moderate response: Week 24 (n=70,73) | 60 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | No response: Week 24 (n=70,73) | 3 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | Good response: 2nd retreatment (n=43,40) | 28 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | No response: 1st retreatment (n=66,67) | 12 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | Moderate response: 1st retreatment (n=66,67) | 53 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | No response: 2nd retreatment (n=43,40) | 19 percentage of participants |
| Randomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | Good response: Week 24 (n=70,73) | 37 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | No response: 2nd retreatment (n=43,40) | 20 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | Good response: Week 24 (n=70,73) | 26 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | Good response: 1st retreatment (n=66,67) | 36 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | Good response: 2nd retreatment (n=43,40) | 30 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | Moderate response: Week 24 (n=70,73) | 71 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | Moderate response: 1st retreatment (n=66,67) | 52 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | Moderate response: 2nd retreatment (n=43,40) | 50 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | No response: Week 24 (n=70,73) | 3 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving a Response During Retreatment by EULAR Category | No response: 1st retreatment (n=66,67) | 12 percentage of participants |
Secondary
Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2)
Percentage of participants with clinical remission and low disease activity as measured by DAS28-CRP for Arm A and Arm B at Week 24 of the Initial Treatment, at 24 weeks after first re-treatment, and at 24 weeks after second retreatment. DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity and \<2.6 = remission.
Time frame: Week 24 of the Initial Treatment, 24 weeks after first retreatment, and 24 weeks after second retreatment
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Group | Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) | Remission: 1st Re-treatment, Week 24 (n=66,67) | 18.2 percentage of participants |
| Randomized Group | Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) | Low activity: Initial Treatment, Week 24 (n=70,73) | 37.1 percentage of participants |
| Randomized Group | Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) | Remission: Initial Treatment, Week 24 (n=70,73) | 14.3 percentage of participants |
| Randomized Group | Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) | Low activity: 1st Retreatment, Week 24 (n=66,67) | 34.8 percentage of participants |
| Randomized Group | Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) | Low activity: 2nd Retreatment, Week 24 (n=43,40) | 27.9 percentage of participants |
| Randomized Group | Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) | Remission: 2nd Retreatment, Week 24 (n=43,40) | 16.3 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) | Low activity: 2nd Retreatment, Week 24 (n=43,40) | 30.0 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) | Remission: Initial Treatment, Week 24 (n=70,73) | 8.2 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) | Remission: 1st Re-treatment, Week 24 (n=66,67) | 9.0 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) | Remission: 2nd Retreatment, Week 24 (n=43,40) | 7.5 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) | Low activity: Initial Treatment, Week 24 (n=70,73) | 27.4 percentage of participants |
| Nonrandomized Group | Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) | Low activity: 1st Retreatment, Week 24 (n=66,67) | 35.8 percentage of participants |
Secondary
Percentage of Participants Reporting Acceptable Disease Activity Symptom State Assessed Using Patient Acceptable and Unacceptable Symptom State (PASS)
Percentage of participants reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of disease activity they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of disease activity they had during the last 48 hours. In the case of missing data, participants who withdrew from the study because of inefficacy or toxicity were considered unacceptable.
Time frame: Week 24, 12 and 24 weeks after 1st retreatment
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Group | Percentage of Participants Reporting Acceptable Disease Activity Symptom State Assessed Using Patient Acceptable and Unacceptable Symptom State (PASS) | Week 24 | 73.4 percentage of participants |
| Randomized Group | Percentage of Participants Reporting Acceptable Disease Activity Symptom State Assessed Using Patient Acceptable and Unacceptable Symptom State (PASS) | 1st retreatment, Week 12 | 73.3 percentage of participants |
| Randomized Group | Percentage of Participants Reporting Acceptable Disease Activity Symptom State Assessed Using Patient Acceptable and Unacceptable Symptom State (PASS) | 1st retreatment, Week 24 | 70.5 percentage of participants |
| Nonrandomized Group | Percentage of Participants Reporting Acceptable Disease Activity Symptom State Assessed Using Patient Acceptable and Unacceptable Symptom State (PASS) | Week 24 | 75.4 percentage of participants |
| Nonrandomized Group | Percentage of Participants Reporting Acceptable Disease Activity Symptom State Assessed Using Patient Acceptable and Unacceptable Symptom State (PASS) | 1st retreatment, Week 12 | 62.5 percentage of participants |
| Nonrandomized Group | Percentage of Participants Reporting Acceptable Disease Activity Symptom State Assessed Using Patient Acceptable and Unacceptable Symptom State (PASS) | 1st retreatment, Week 24 | 64.3 percentage of participants |
Secondary
Percentage of Participants Reporting Acceptable Symptom State in Functioning Assessed Using PASS
Percentage of participants reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of function they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of function they had during the last 48 hours. In the case of missing data, participants who withdrew from the study because of inefficacy or toxicity were considered unacceptable.
Time frame: Week 24, 12 and 24 weeks after 1st retreatment
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Group | Percentage of Participants Reporting Acceptable Symptom State in Functioning Assessed Using PASS | Week 24 | 74.2 percentage of participants |
| Randomized Group | Percentage of Participants Reporting Acceptable Symptom State in Functioning Assessed Using PASS | 1st retreatment, Week 12 | 75.9 percentage of participants |
| Randomized Group | Percentage of Participants Reporting Acceptable Symptom State in Functioning Assessed Using PASS | 1st retreatment, Week 24 | 70.2 percentage of participants |
| Nonrandomized Group | Percentage of Participants Reporting Acceptable Symptom State in Functioning Assessed Using PASS | Week 24 | 72.7 percentage of participants |
| Nonrandomized Group | Percentage of Participants Reporting Acceptable Symptom State in Functioning Assessed Using PASS | 1st retreatment, Week 12 | 60.0 percentage of participants |
| Nonrandomized Group | Percentage of Participants Reporting Acceptable Symptom State in Functioning Assessed Using PASS | 1st retreatment, Week 24 | 62.1 percentage of participants |
Secondary
Percentage of Participants With Acceptable Symptom State in Pain Assessed Using PASS
Percentage of participants reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of pain they had during the last 48 hours. In the case of missing data, participants who withdrew from the study because of inefficacy or toxicity were considered unacceptable.
Time frame: Week 24, 12 and 24 weeks after 1st retreatment
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Group | Percentage of Participants With Acceptable Symptom State in Pain Assessed Using PASS | Week 24 | 74.2 percentage of participants |
| Randomized Group | Percentage of Participants With Acceptable Symptom State in Pain Assessed Using PASS | 1st retreatment Week 12 | 70.2 percentage of participants |
| Randomized Group | Percentage of Participants With Acceptable Symptom State in Pain Assessed Using PASS | 1st retreatment, Week 24 | 72.9 percentage of participants |
| Nonrandomized Group | Percentage of Participants With Acceptable Symptom State in Pain Assessed Using PASS | Week 24 | 75.0 percentage of participants |
| Nonrandomized Group | Percentage of Participants With Acceptable Symptom State in Pain Assessed Using PASS | 1st retreatment Week 12 | 61.8 percentage of participants |
| Nonrandomized Group | Percentage of Participants With Acceptable Symptom State in Pain Assessed Using PASS | 1st retreatment, Week 24 | 61.4 percentage of participants |
Secondary
Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment
Anti-CCP antibodies are auto antibodies (antibodies directed against 1 or more of an individual's own proteins) that are frequently detected in the blood of rheumatoid arthritis participants. Anti-CCP antibodies value higher than 10 U/mL is considered positive.
Time frame: Week 24 of the initial treatment, 24 weeks after first re-treatment, and 24 weeks after second retreatment
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Group | Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment | Negative: Initial treatment, Week 24 (n=69,71) | 17.4 percentage of participants |
| Randomized Group | Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment | Positive: Initial treatment, Week 24 (n=69,71) | 82.6 percentage of participants |
| Randomized Group | Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment | Negative: 1st Retreatment, Week 24 (n=44,43) | 22.7 percentage of participants |
| Randomized Group | Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment | Positive: 1st Retreatment, Week 24 (n=44,43) | 77.3 percentage of participants |
| Randomized Group | Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment | Negative: 2nd retreatment, Week 24 (n=15,12) | 13.3 percentage of participants |
| Randomized Group | Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment | Positive: 2nd retreatment, Week 24 (n=15,12) | 86.7 percentage of participants |
| Nonrandomized Group | Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment | Negative: 2nd retreatment, Week 24 (n=15,12) | 41.7 percentage of participants |
| Nonrandomized Group | Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment | Negative: Initial treatment, Week 24 (n=69,71) | 22.5 percentage of participants |
| Nonrandomized Group | Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment | Positive: 1st Retreatment, Week 24 (n=44,43) | 79.1 percentage of participants |
| Nonrandomized Group | Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment | Positive: Initial treatment, Week 24 (n=69,71) | 77.5 percentage of participants |
| Nonrandomized Group | Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment | Positive: 2nd retreatment, Week 24 (n=15,12) | 58.3 percentage of participants |
| Nonrandomized Group | Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment | Negative: 1st Retreatment, Week 24 (n=44,43) | 20.9 percentage of participants |
Secondary
Percentage of Participants With MCII in Functioning
Participants were asked how their functioning had been during the last 48 hours compared to baseline. Those participants that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse.
Time frame: Week 24, 12 and 24 weeks after 1st retreatment
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Group | Percentage of Participants With MCII in Functioning | Week 24 | 73.4 percentage of participants |
| Randomized Group | Percentage of Participants With MCII in Functioning | 1st retreatment, Week 12 | 65.0 percentage of participants |
| Randomized Group | Percentage of Participants With MCII in Functioning | 1st retreatment, Week 24 | 65.5 percentage of participants |
| Nonrandomized Group | Percentage of Participants With MCII in Functioning | 1st retreatment, Week 24 | 57.9 percentage of participants |
| Nonrandomized Group | Percentage of Participants With MCII in Functioning | Week 24 | 76.5 percentage of participants |
| Nonrandomized Group | Percentage of Participants With MCII in Functioning | 1st retreatment, Week 12 | 63.0 percentage of participants |
Secondary
Percentage of Participants With MCII in Pain
Participants were asked how their pain had been during the last 48 hours compared to baseline. Those participants that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse pain.
Time frame: Week 24, 12 and 24 weeks after 1st retreatment
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Group | Percentage of Participants With MCII in Pain | Week 24 (n=63,70) | 76.2 percentage of participants |
| Randomized Group | Percentage of Participants With MCII in Pain | 1st retreatment, Week 12 (n=59,55) | 71.2 percentage of participants |
| Randomized Group | Percentage of Participants With MCII in Pain | 1st retreatment, Week 24 (n=61,57) | 68.9 percentage of participants |
| Nonrandomized Group | Percentage of Participants With MCII in Pain | Week 24 (n=63,70) | 80.0 percentage of participants |
| Nonrandomized Group | Percentage of Participants With MCII in Pain | 1st retreatment, Week 12 (n=59,55) | 69.1 percentage of participants |
| Nonrandomized Group | Percentage of Participants With MCII in Pain | 1st retreatment, Week 24 (n=61,57) | 61.4 percentage of participants |
Secondary
Percentage of Participants With Minimum Clinically Important Improvement (MCII) in Disease Activity
Participants were asked how their disease activity had been during the last 48 hours compared to baseline. Those participants that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse-more disease activity.
Time frame: Week 24, 12 and 24 weeks after 1st retreatment
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Group | Percentage of Participants With Minimum Clinically Important Improvement (MCII) in Disease Activity | 1st retreatment, Week 24 | 66.7 percentage of participants |
| Randomized Group | Percentage of Participants With Minimum Clinically Important Improvement (MCII) in Disease Activity | Week 24 | 75.4 percentage of participants |
| Randomized Group | Percentage of Participants With Minimum Clinically Important Improvement (MCII) in Disease Activity | 1st retreatment, Week 12 | 65.6 percentage of participants |
| Nonrandomized Group | Percentage of Participants With Minimum Clinically Important Improvement (MCII) in Disease Activity | Week 24 | 81.2 percentage of participants |
| Nonrandomized Group | Percentage of Participants With Minimum Clinically Important Improvement (MCII) in Disease Activity | 1st retreatment, Week 12 | 63.0 percentage of participants |
| Nonrandomized Group | Percentage of Participants With Minimum Clinically Important Improvement (MCII) in Disease Activity | 1st retreatment, Week 24 | 66.1 percentage of participants |
Secondary
Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment
RF is the auto antibody directed against immunoglobulin G (IgG) and its concentration is observed in human serum or plasma. RF value higher than 20 international units per milliliter (IU/mL) is considered positive.
Time frame: Week 24 of the initial treatment, 24 weeks after first re-treatment, and 24 weeks after second retreatment
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Randomized Group | Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment | Positive: 1st Retreatment, Week 24 (n=44,43) | 63.6 percentage of participants | 75.68 |
| Randomized Group | Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment | Negative: Initial treatment, Week 24 (n=69,71) | 33.3 percentage of participants | 273.09 |
| Randomized Group | Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment | Negative: 2nd retreatment, Week 24 (n=15,12) | 46.7 percentage of participants | — |
| Randomized Group | Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment | Negative: 1st Retreatment, Week 24 (n=44,43) | 36.4 percentage of participants | 79.14 |
| Randomized Group | Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment | Positive: 2nd retreatment, Week 24 (n=15,12) | 53.3 percentage of participants | — |
| Randomized Group | Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment | Positive: Initial treatment, Week 24 (n=69,71) | 66.7 percentage of participants | 114.63 |
| Nonrandomized Group | Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment | Positive: 2nd retreatment, Week 24 (n=15,12) | 16.7 percentage of participants | — |
| Nonrandomized Group | Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment | Positive: Initial treatment, Week 24 (n=69,71) | 62.0 percentage of participants | 386.02 |
| Nonrandomized Group | Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment | Negative: 1st Retreatment, Week 24 (n=44,43) | 48.8 percentage of participants | 65.29 |
| Nonrandomized Group | Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment | Positive: 1st Retreatment, Week 24 (n=44,43) | 51.2 percentage of participants | 41.01 |
| Nonrandomized Group | Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment | Negative: 2nd retreatment, Week 24 (n=15,12) | 83.3 percentage of participants | — |
| Nonrandomized Group | Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment | Negative: Initial treatment, Week 24 (n=69,71) | 38.0 percentage of participants | 408.24 |
Secondary
Physician's Global Assessment of Disease Activity
The Physician's Global Assessment of disease activity is assessed on a 0 to 100 millimeter (mm) horizontal VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as maximum disease activity (maximum arthritis disease activity). Physicians were asked to mark the line and the distance from the left edge was measured. Higher values correspond to worst state of participant (high disease activity).
Time frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | Physician's Global Assessment of Disease Activity | Initial treatment, Day 1 (n=70,73) | 65.0 mm | Standard Deviation 15 |
| Randomized Group | Physician's Global Assessment of Disease Activity | Initial treatment, Week 24 (n=69,71) | 27.9 mm | Standard Deviation 18.6 |
| Randomized Group | Physician's Global Assessment of Disease Activity | Before 1st retreatment (n=64,63) | 33.7 mm | Standard Deviation 17.4 |
| Randomized Group | Physician's Global Assessment of Disease Activity | 1st retreatment, Day 1 (n=60,61) | 44.4 mm | Standard Deviation 20.8 |
| Randomized Group | Physician's Global Assessment of Disease Activity | 1st retreatment, Week 12 (n=56,62) | 30.4 mm | Standard Deviation 18.8 |
| Randomized Group | Physician's Global Assessment of Disease Activity | 1st retreatment, Week 24 (n=60,59) | 31.9 mm | Standard Deviation 19.1 |
| Nonrandomized Group | Physician's Global Assessment of Disease Activity | Before 1st retreatment (n=64,63) | 26.9 mm | Standard Deviation 17.1 |
| Nonrandomized Group | Physician's Global Assessment of Disease Activity | Initial treatment, Day 1 (n=70,73) | 64.1 mm | Standard Deviation 15 |
| Nonrandomized Group | Physician's Global Assessment of Disease Activity | 1st retreatment, Week 12 (n=56,62) | 28.4 mm | Standard Deviation 18 |
| Nonrandomized Group | Physician's Global Assessment of Disease Activity | 1st retreatment, Week 24 (n=60,59) | 24.8 mm | Standard Deviation 16.3 |
| Nonrandomized Group | Physician's Global Assessment of Disease Activity | Initial treatment, Week 24 (n=69,71) | 27.2 mm | Standard Deviation 16.2 |
| Nonrandomized Group | Physician's Global Assessment of Disease Activity | 1st retreatment, Day 1 (n=60,61) | 43.3 mm | Standard Deviation 18.5 |
Secondary
SF-12 Mental Health Composite Score
Mental Health Composite Scores of SF-12 were computed using the scores of 12 questions and range from 0 to 100, where a 0 score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | SF-12 Mental Health Composite Score | Initial treatment, Day 1 (n=62,65) | 36.03 units on a scale | Standard Deviation 10.03 |
| Randomized Group | SF-12 Mental Health Composite Score | Initial treatment, Week 24 (n=63,68) | 43.08 units on a scale | Standard Deviation 9.74 |
| Randomized Group | SF-12 Mental Health Composite Score | Before 1st retreatment (n=21,22) | 44.94 units on a scale | Standard Deviation 9.94 |
| Randomized Group | SF-12 Mental Health Composite Score | 1st retreatment, Day 1 (n=47,44) | 40.87 units on a scale | Standard Deviation 10.53 |
| Randomized Group | SF-12 Mental Health Composite Score | 1st retreatment, Week 12 (n=13,10) | 41.84 units on a scale | Standard Deviation 11.36 |
| Randomized Group | SF-12 Mental Health Composite Score | 1st retreatment, Week 24 (n=40,36) | 40.90 units on a scale | Standard Deviation 10.61 |
| Nonrandomized Group | SF-12 Mental Health Composite Score | 1st retreatment, Week 12 (n=13,10) | 34.69 units on a scale | Standard Deviation 11.06 |
| Nonrandomized Group | SF-12 Mental Health Composite Score | Initial treatment, Day 1 (n=62,65) | 37.13 units on a scale | Standard Deviation 9.4 |
| Nonrandomized Group | SF-12 Mental Health Composite Score | 1st retreatment, Day 1 (n=47,44) | 38.52 units on a scale | Standard Deviation 7.87 |
| Nonrandomized Group | SF-12 Mental Health Composite Score | Initial treatment, Week 24 (n=63,68) | 40.99 units on a scale | Standard Deviation 9.01 |
| Nonrandomized Group | SF-12 Mental Health Composite Score | 1st retreatment, Week 24 (n=40,36) | 41.60 units on a scale | Standard Deviation 8.87 |
| Nonrandomized Group | SF-12 Mental Health Composite Score | Before 1st retreatment (n=21,22) | 41.57 units on a scale | Standard Deviation 8.66 |
Secondary
Short Form 12 (SF-12) Physical Health Composite Score
Physical and Mental Health Composite Scores of SF-12 were computed using the scores of 12 questions and range from 0 to 100, where a 0 score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | Short Form 12 (SF-12) Physical Health Composite Score | Initial treatment, Day 1 (n=62,65) | 31.11 units on a scale | Standard Deviation 7.55 |
| Randomized Group | Short Form 12 (SF-12) Physical Health Composite Score | Initial Tteatment, Week 24 (n=63,68) | 38.81 units on a scale | Standard Deviation 8.39 |
| Randomized Group | Short Form 12 (SF-12) Physical Health Composite Score | Before 1st retreatment (n=21,22) | 39.44 units on a scale | Standard Deviation 8.45 |
| Randomized Group | Short Form 12 (SF-12) Physical Health Composite Score | 1st retreatment, Day 1 (n=47,44) | 36.57 units on a scale | Standard Deviation 6.75 |
| Randomized Group | Short Form 12 (SF-12) Physical Health Composite Score | 1st retreatment, Week 12 (n=13,10) | 38.36 units on a scale | Standard Deviation 9.3 |
| Randomized Group | Short Form 12 (SF-12) Physical Health Composite Score | 1st retreatment, Week 24 (n=40,36) | 36.53 units on a scale | Standard Deviation 7.75 |
| Nonrandomized Group | Short Form 12 (SF-12) Physical Health Composite Score | 1st retreatment, Week 12 (n=13,10) | 38.05 units on a scale | Standard Deviation 10.77 |
| Nonrandomized Group | Short Form 12 (SF-12) Physical Health Composite Score | Initial treatment, Day 1 (n=62,65) | 31.07 units on a scale | Standard Deviation 7.41 |
| Nonrandomized Group | Short Form 12 (SF-12) Physical Health Composite Score | 1st retreatment, Day 1 (n=47,44) | 35.81 units on a scale | Standard Deviation 8.97 |
| Nonrandomized Group | Short Form 12 (SF-12) Physical Health Composite Score | Initial Tteatment, Week 24 (n=63,68) | 40.05 units on a scale | Standard Deviation 8.64 |
| Nonrandomized Group | Short Form 12 (SF-12) Physical Health Composite Score | 1st retreatment, Week 24 (n=40,36) | 36.86 units on a scale | Standard Deviation 8.13 |
| Nonrandomized Group | Short Form 12 (SF-12) Physical Health Composite Score | Before 1st retreatment (n=21,22) | 39.52 units on a scale | Standard Deviation 9.99 |
Secondary
Time to Achieve DAS28-CRP ≤3.2 After Retreatment
DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity.
Time frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
Population: ITT population; n=number of participants assessed at a given visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Randomized Group | Time to Achieve DAS28-CRP ≤3.2 After Retreatment | 1st retreatment (n=66,68) | 31.0 weeks |
| Randomized Group | Time to Achieve DAS28-CRP ≤3.2 After Retreatment | 2nd retreatment (n=49,48) | 16.9 weeks |
| Nonrandomized Group | Time to Achieve DAS28-CRP ≤3.2 After Retreatment | 1st retreatment (n=66,68) | 22.1 weeks |
| Nonrandomized Group | Time to Achieve DAS28-CRP ≤3.2 After Retreatment | 2nd retreatment (n=49,48) | 29.0 weeks |
Secondary
Time to Achieve DAS28-CRP ≤3.2 After the First Course of Treatment
DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity.
Time frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized Group | Time to Achieve DAS28-CRP ≤3.2 After the First Course of Treatment | 28.0 weeks |
Secondary
Time to Achieve DAS28-CRP Remission After Retreatment
DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP \<2.6=remission.
Time frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
Population: ITT population; n=number of participants assessed at a given visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Randomized Group | Time to Achieve DAS28-CRP Remission After Retreatment | 1st retreatment (n=66,68) | NA weeks |
| Randomized Group | Time to Achieve DAS28-CRP Remission After Retreatment | 2nd retreatment (n=49,48) | NA weeks |
| Nonrandomized Group | Time to Achieve DAS28-CRP Remission After Retreatment | 1st retreatment (n=66,68) | 78.1 weeks |
| Nonrandomized Group | Time to Achieve DAS28-CRP Remission After Retreatment | 2nd retreatment (n=49,48) | NA weeks |
Secondary
Time to Achieve DAS28-CRP Remission After the First Course
DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP \<2.6=remission.
Time frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized Group | Time to Achieve DAS28-CRP Remission After the First Course | 56.0 weeks |
Secondary
Total Mean Dose of Cortisone Between Week 24 and Week 104
All cortisone intakes were taken into account, including oral, IV (including the cortisone administration before the rituximab infusion), intramuscular and intra-articular.
Time frame: Week 24 to Week 104
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Group | Total Mean Dose of Cortisone Between Week 24 and Week 104 | Total cortisone: Week 24 to Week 104 | 2542.9 mg | Standard Deviation 2085.6 |
| Randomized Group | Total Mean Dose of Cortisone Between Week 24 and Week 104 | Oral cortisone: Week 24 to Week 104 | 2384.0 mg | Standard Deviation 2092.6 |
| Randomized Group | Total Mean Dose of Cortisone Between Week 24 and Week 104 | IV cortisone: Week 24 to Week 104 | 199.1 mg | Standard Deviation 92.3 |
| Nonrandomized Group | Total Mean Dose of Cortisone Between Week 24 and Week 104 | Total cortisone: Week 24 to Week 104 | 2842.5 mg | Standard Deviation 2124.9 |
| Nonrandomized Group | Total Mean Dose of Cortisone Between Week 24 and Week 104 | Oral cortisone: Week 24 to Week 104 | 2425.1 mg | Standard Deviation 2046.6 |
| Nonrandomized Group | Total Mean Dose of Cortisone Between Week 24 and Week 104 | IV cortisone: Week 24 to Week 104 | 384.9 mg | Standard Deviation 193.5 |
Comparison: Total cortisone: Week 24 to Week 104p-value: 0.278Wilcoxon (Mann-Whitney)
Comparison: Oral cortisone: Week 24 to Week 104p-value: 0.887Wilcoxon (Mann-Whitney)
Comparison: IV cortisone: Week 24 to Week 104p-value: <0.001Wilcoxon (Mann-Whitney)