Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis

Abstract

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.)

Intravenous Immunoglobulin as an Immunomodulating Agent in Antineutrophil Cytoplasmic Antibody–Associated Vasculitides: A French Nationwide Study of Ninety‐Two Patients

“…Although the population was heterogeneous, it reflects the features of patients from real life with baseline BVAS and clinical manifestations similar to those observed in patients included in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial (20,21). The findings of our study strongly suggest that IVIG exhibits overall efficacy, with an acceptable safety profile and with remission rates at 12 months that are comparable to those observed in the RAVE trial (20,21). …”

Pregnancy in women diagnosed with Antineutrophil cytoplasmic antibody–associated vasculitis: Outcome for the mother and the child

“…Adequate short-term disease control has been reported, and gonadal toxicity has not been reported and is also not expected with this therapy (28). Rituximab could therefore be the first-choice treatment in young women of childbearing age to prevent gonadal toxicity and fertility-related problems.…”

Immune Mediated Diseases and Immune Modulation in the Neurocritical Care Unit

“…Once diagnosed, induction therapy for treatment of WG usually consists of parenteral corticosteroids and cyclophosphamide [146]. In a recent study in which all patients were treated with highdose corticosteroids to induce remission, rituximab was shown to be as good as cyclophosphamide for treating ANCA-associated vasculitides and better than cyclophosphamide for patients with relapsing-remitting disease [147,148]. There are insufficient data to recommend IVIG for treating WG [149].…”

“…In a recent study in which all patients were treated with high-dose corticosteroids to induce remission, rituximab was shown to be as good as cyclophosphamide for treating AAVs and better than cyclophosphamide for patients with relapsingremitting disease [147,148]. The survival rate for MPA is reported to be 45 to 76% at 5 years [136,151].…”

“…A typical dose of oral cyclophosphamide for the treatment of vasculitis is 2 mg/kg with a maximum of 150 mg/day (adjusted dose in renal insufficiency) daily for 4 weeks [147]. Typical dosing of intravenous cyclophosphamide for the treatment of primary CNS vasculitis is 15 mg/kg every 2 to 3 weeks [343].…”