Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis
By John H. Stone, P. Merkel, R. Spiera, P. Seo, C. Langford, G. Hoffman, C. Kallenberg, E. S. St Clair, A. Turkiewicz, N. Tchao and 19 more. New England Journal of Medicine, 2010
2,370 citations recorded by the source corpus.
BACKGROUND Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. METHODS We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. RESULTS Nine centers enrolled 197 ANCA-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P = 0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. CONCLUSIONS Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.)
Subfields: Pathology and Forensic Medicine, Pulmonary and Respiratory Medicine, Rheumatology
View Paper: https://www.semanticscholar.org/paper/8566ef7ed8c5b4d14e8ba7b65f1c698db3f60b9d
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Citations in the corpus
- KDIGO Clinical Practice Guideline for Glomerulonephritis (2012, background): “03).(714) Although more experience will be needed with the use of rituximab for treatment of severe relapses, and although the long-term safety of rituximab remains uncertain, its use in relapse may provide an opportunity to minimize cumulative dosage and avoid the potential long-term toxicity of cy”
- ImmPort: disseminating data to the public for the future of immunology (2014, background): “…(NCT00104299, ImmPort: SDY91) was a prospective, randomized, controlled phase 2–3 study comparing the anti-CD20 monoclonal antibody rituximab against cyclophosphamide for the treatment of Wegener’s granuloma-tosis and microscopic polyangiitis, published in the New England Journal of Medicine [12].”
- EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis (2016, background): “56 57 In both studies patients initially received high-dose glucocorticoids with subsequent dose tapering.”