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

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

Guidelines

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.