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RAVE

"Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis". The New England Journal of Medicine. 2010. 363:221-232. PubMed•Full

Links to original sources: Wiki Journal Post Full Journal Article

Contents 1 Clinical Question 2 Bottom Line 3 Major Points 4 Guidelines 5 Design 6 Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Baseline Characteristics 7 Interventions 8 Outcomes 8.1 Primary Outcome 8.2 Secondary Outcomes 9 Criticisms 10 Funding 11 Further Reading

Clinical Question


In patients with ANCA-associated vasculitis, is rituximab as effective as cyclophosphamide for inducing remission?

Bottom Line


Rituximab was not inferior to cyclophosphamide for inducing remission in patients with severe ANCA-associated vasculitis and may be superior in patients with relapsing disease.

Major Points


ANCA-associated vasculitis, which includes Wegener's granulomatosis and microscopic polyangiitis, has traditionally been treated with cyclophosphamide and glucocorticoids for remission induction. Rituximab, an anti-CD20 monoclonal antibody, has shown promise in uncontrolled studies for remission induction in ANCA-associated vasculitis. The Rituximab in ANCA-Associated Vasculitis (RAVE) trial demonstrated that rituximab was not inferior to cyclophosphamide for inducing remission and may be superior in relapsing disease.

Guidelines


No formal guidelines were discussed in this article. However, the RAVE trial contributes significantly to the evidence base for using rituximab in the management of ANCA-associated vasculitis.

Design


Multicenter, randomized, double-blind, double-dummy, noninferiority trial

Population


Inclusion Criteria: ANCA-positive patients with Wegener's granulomatosis or microscopic polyangiitis and a BVAS/WG score of ≥3. Exclusion Criteria: Severe alveolar hemorrhage requiring ventilatory support or advanced renal dysfunction (serum creatinine >4.0 mg/dL). Baseline Characteristics: Similar between two groups, including disease activity, organ involvement, and proportion of relapsing disease.

Interventions


Rituximab group received intravenous rituximab (375 mg/m^2 weekly for 4 weeks) plus daily placebo-cyclophosphamide. Control group received placebo-rituximab infusions plus daily cyclophosphamide (2 mg/kg per day). Both groups were tapered off of glucocorticoids.

Outcomes


Primary Outcome: Remission of disease without prednisone use at 6 months. Secondary Outcomes: Rates of disease flares, BVAS/WG score, cumulative glucocorticoid doses, rates of adverse events, and quality of life (SF-36 scores).

Criticisms


Long-term management, including retreatment with rituximab, was not addressed. The trial only included patients with severe ANCA-associated vasculitis who were ANCA-positive.

Funding


National Institute of Allergy and Infectious Diseases, Genentech, Biogen, and others.

Further Reading


The full article text and supplementary materials are available at The New England Journal of Medicine.