RAVE
Trial question
Is rituximab noninferior to cyclophosphamide in patients with severe ANCA-associated vasculitis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
49.0% female
51.0% male
N = 197
197 patients (97 female, 100 male).
Inclusion criteria: ANCA-positive patients with either Wegener's granulomatosis or microscopic polyangiitis.
Key exclusion criteria: Churg-Strauss syndrome or anti-GBM disease, alveolar hemorrhage severe enough to require mechanical ventilation, renal failure, active systemic infection, osteomyelitis, septic arthritis, or pneumonia complicated by empyema, or severe liver disease.
Interventions
N=99 rituximab (intravenous 375 mg per square meter of body-surface area per week for 4 weeks plus corticosteroid regimen).
N=98 cyclophosphamide (2 mg/kg of body weight per day, adjusted for renal insufficiency plus corticosteroid regimen).
Primary outcome
Remission of disease without use of prednisone at 6 months
64%
53%
64.0 %
48.0 %
32.0 %
16.0 %
0.0 %
Rituximab
Cyclophosphamide
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in remission of disease without the use of prednisone at 6 months (64% vs. 53%; ARD 11, 95% CI 4.47 to 17.53).
Secondary outcomes
Significant increase in remission induction of relapsing disease (67% vs. 42%; RR 1.6, 95% CI 0.38 to 2.82).
Significant increase in the rate of ANCA response, by 6 months (47% vs. 24%; RR 1.96, 95% CI 0.63 to 3.29).
Safety outcomes
No significant difference in rates of total or serious adverse events.
Conclusion
In ANCA-positive patients with either Wegener's granulomatosis or microscopic polyangiitis, rituximab was noninferior to cyclophosphamide with respect to remission of disease without the use of prednisone at 6 months.
Reference
Stone JH, Merkel PA, Spiera R et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32.
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