PDF: MAINRITSAN
(2014)Objective
To compare rituximab versus azathioprine for maintenance of remission in ANCA-associated vasculitides after cyclophosphamide-glucocorticoid induction
Study Summary
• NNT with rituximab to prevent 1 major relapse: 4 (95% CI 3-9)
• Minor relapses: 11% rituximab vs 16% azathioprine (P=0.43)
• Severe adverse events: 25 patients per group (P=0.92)
• Severe infections: 14% azathioprine vs 19% rituximab
• Deaths: 2 in azathioprine group (sepsis, pancreatic cancer), 0 in rituximab group
Intervention
Rituximab 500 mg IV on days 0, 14 and at months 6, 12, 18 after randomization vs azathioprine 2 mg/kg/day tapering over 22 months; both groups received prednisone tapering
Inclusion Criteria
Age 18-75; newly diagnosed or relapsing GPA, MPA, or renal-limited ANCA-associated vasculitis; in complete remission (BVAS 0) after cyclophosphamide-glucocorticoid induction; ANCA-positive at diagnosis or during disease. Excluded: prior rituximab or biologic therapy
Study Design
Arms: Array
Patients per Arm: Rituximab: 57; Azathioprine: 58
Outcome
• NNT: 4 (3-9)
• Minor relapse: 11% vs 16% (P=0.43)
• Severe adverse events similar between groups
• 2 deaths in azathioprine group, 0 in rituximab
Bottom Line
Rituximab maintenance therapy was markedly superior to azathioprine for preventing major relapses in ANCA-associated vasculitis (5% vs 29% at month 28, HR 6.61, P=0.002). The NNT was 4 to prevent one major relapse. Severe adverse event rates were similar. This trial established rituximab as the preferred maintenance therapy for AAV.
Major Points
- MAINRITSAN was a non-blinded, randomized, controlled trial enrolling 118 patients with newly diagnosed or relapsing GPA, MPA, or renal-limited ANCA-associated vasculitis in France.
- All patients achieved complete remission (BVAS 0) after cyclophosphamide-glucocorticoid induction before randomization.
- Patients were randomized 1:1 to rituximab (500 mg IV on days 0, 14, and months 6, 12, 18) or azathioprine (2 mg/kg/day tapering over 22 months).
- At month 28, major relapse occurred in 3/57 (5%) rituximab patients vs 17/58 (29%) azathioprine patients (HR 6.61, 95% CI 1.56-27.96, P=0.002).
- The number needed to treat with rituximab to prevent one major relapse was 4 (95% CI 3-9).
- Minor relapses occurred in 11% (rituximab) vs 16% (azathioprine), P=0.43.
- Severe adverse events occurred in 25 patients per group (P=0.92). Two deaths occurred in the azathioprine group (sepsis, pancreatic cancer).
- A lower rituximab dose (500 mg rather than 375 mg/m2) was chosen based on its established efficacy for rheumatoid arthritis maintenance.
Study Design
- Study Type
- Multicenter, randomized, open-label, controlled trial
- Randomization
- Yes
- Blinding
- Non-blinded; patients, investigators, and data committee aware of assignments
- Sample Size
- 115
- Follow-up
- 28 months (10 or 6 months after last rituximab or azathioprine dose)
- Countries
- France
Primary Outcome
Definition: Major relapse at month 28: 5% (rituximab) vs 29% (azathioprine); HR 6.61 (95% CI 1.56-27.96), P=0.002
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 6.61 (1.56-27.96) | P=0.002 |
Citation
N Engl J Med 2014;371:1771-80