Phase 3
Completed N=224
SMART Study: A Study of Re-treatment With MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Failed on Anti-TNF Alfa Therapy
Source: ClinicalTrials.gov NCT01126541 ↗Enrolled (actual)
224
Serious AEs
27.9%
Results posted
Sep 2014
Primary outcomePrimary: Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (DAS28-CRP) Area Under the Curve (AUC) at Week 104 — 2761.4; 2666.0 score on a scale*week
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (DAS28-CRP) Area Under the Curve (AUC) at Week 104 |
2761.4; 2666.0 | — |
| SECONDARY DAS28-CRP During the Initial Treatment |
5.82; 5.77; 5.33; 5.42; 4.69; 5.12 | — |
| SECONDARY DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course |
5.79; 5.84; 3.57; 3.73; -2.22; -2.11 | 0.465 |
| SECONDARY Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) |
14.3; 8.2; 18.2; 9.0; 16.3; 7.5 | — |
| SECONDARY DAS28-CRP AUC Weighted Time |
3.82; 3.88 | — |
| SECONDARY Time to Achieve DAS28-CRP Remission After the First Course |
56.0 | — |
| SECONDARY Time to Achieve DAS28-CRP Remission After Retreatment |
NA; 78.1; NA; NA | — |
| SECONDARY Time to Achieve DAS28-CRP ≤3.2 After the First Course of Treatment |
28.0 | — |
| SECONDARY Time to Achieve DAS28-CRP ≤3.2 After Retreatment |
31.0; 22.1; 16.9; 29.0 | — |
| SECONDARY Duration of DAS28-CRP Remission After the First Course of Treatment |
11.7 | — |
| SECONDARY Duration of DAS28-CRP Remission After Retreatment |
16.0; 8.0; 9.0; 8.0 | — |
| SECONDARY Duration of DAS28-CRP ≤3.2 After the First Course of Treatment |
14.3 | — |
| SECONDARY Duration of DAS28-CRP ≤3.2 After Retreatment |
27.0; 17.0; 10.1; 16.0 | — |
| SECONDARY Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) |
78.6; 75.3; 63.6; 61.2; 65.1; 60.0 | — |
| SECONDARY Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category |
4; 3; 5; 4; 15; 4 | — |
| SECONDARY Percentage of Participants Achieving a Response During Retreatment by EULAR Category |
37; 26; 35; 36; 28; 30 | — |
| SECONDARY Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment |
33.3; 38.0; 66.7; 62.0; 36.4; 48.8 | — |
| SECONDARY Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment |
17.4; 22.5; 82.6; 77.5; 22.7; 20.9 | — |
| SECONDARY Physician's Global Assessment of Disease Activity |
65.0; 64.1; 27.9; 27.2; 33.7; 26.9 | — |
| SECONDARY Patient Global Assessment of Disease Activity |
63.0; 64.2; 29.9; 32.6; 33.2; 34.7 | — |
| SECONDARY Patient's Global Assessment of Pain |
61.9; 60.1; 28.5; 30.0; 34.4; 32.9 | — |
| SECONDARY Participant Assessment of Fatigue |
62.1; 62.0; 37.1; 39.8; 44.5; 41.2 | — |
| SECONDARY Cortisone Intake AUC (Time- and Weight-Weighted) |
0.08; 0.09; 0.08; 0.09; 0.08; 0.09 | 0.389 |
| SECONDARY Total Mean Dose of Cortisone Between Week 24 and Week 104 |
2542.9; 2842.5; 2384.0; 2425.1; 199.1; 384.9 | 0.278 |
| SECONDARY HAQ-DI Scores |
1.74; 1.75; 1.25; 1.31; 1.26; 1.35 | — |
| SECONDARY Short Form 12 (SF-12) Physical Health Composite Score |
31.11; 31.07; 38.81; 40.05; 39.44; 39.52 | — |
| SECONDARY SF-12 Mental Health Composite Score |
36.03; 37.13; 43.08; 40.99; 44.94; 41.57 | — |
| SECONDARY Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index |
52.15; 49.89; 43.73; 40.50; 45.44; 41.27 | — |
| SECONDARY Percentage of Participants Reporting Acceptable Disease Activity Symptom State Assessed Using Patient Acceptable and Unacceptable Symptom State (PASS) |
73.4; 75.4; 73.3; 62.5; 70.5; 64.3 | — |
| SECONDARY Patient Global Assessment of Disease Activity in Participants Reporting Acceptable Symptoms Using PASS |
23.4; 28.4; 27.4; 27.3; 26.3; 25.7 | — |
| SECONDARY Percentage of Participants With Minimum Clinically Important Improvement (MCII) in Disease Activity |
75.4; 81.2; 65.6; 63.0; 66.7; 66.1 | — |
| SECONDARY Change From Baseline in Patient Global Assessment of Disease Activity in Participants With MCII |
-12.4; -4.6; -4.2; -9.2; -2.5; -2.9 | — |
| SECONDARY Percentage of Participants Reporting Acceptable Symptom State in Functioning Assessed Using PASS |
74.2; 72.7; 75.9; 60.0; 70.2; 62.1 | — |
| SECONDARY HAQ-DI Scores in Participants Reporting Acceptable Function Using PASS |
1.16; 1.16; 1.20; 1.08; 1.14; 1.08 | — |
| SECONDARY Percentage of Participants With MCII in Functioning |
73.4; 76.5; 65.0; 63.0; 65.5; 57.9 | — |
| SECONDARY Change From Baseline in HAQ-DI in Participants With MCII |
-0.11; -0.06; -0.03; -0.11; -0.07; -0.09 | — |
| SECONDARY Percentage of Participants With Acceptable Symptom State in Pain Assessed Using PASS |
74.2; 75.0; 70.2; 61.8; 72.9; 61.4 | — |
| SECONDARY Patient Global Assessment of Pain in Participants Reporting Acceptable Symptoms Using PASS |
21.5; 26.4; 26.8; 27.6; 26.3; 25.1 | — |
| SECONDARY Percentage of Participants With MCII in Pain |
76.2; 80.0; 71.2; 69.1; 68.9; 61.4 | — |
| SECONDARY Change From Baseline in Patient Global Assessment of Pain in Participants With MCII |
-13.5; -4.3; -2.7; -8.9; -3.5; -3.2 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01126541). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.