Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis

Abstract

Background The 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is unknown. Methods In a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months. Results A total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide–azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (P<0.001, with a noninferiority margin of 20%). There was no significant difference between the groups in any efficacy measure, including the duration of complete remission and the frequency or severity of relapses. Among the 101 patients who had relapsing disease at baseline, rituximab was superior to conventional immunosuppression at 6 months (P = 0.01) and at 12 months (P = 0.009) but not at 18 months (P = 0.06), at which time most patients in the rituximab group had reconstituted B cells. There was no significant between-group difference in adverse events. Conclusions In patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the National Institute of Allergy and Infectious Diseases and others; RAVE 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). …”

Is Newer Safer? Adverse Events Associated with First-Line Therapies for ANCA-Associated Vasculitis and Lupus Nephritis

“…Rituximab met criterion for noninferiority; 64% of patients reached the primary endpoint compared with 53% in the CYC group (P,0.001). Longer follow-up of the RAVE trial found sustained remission rates of 48% and 39% with rituximab at 12 and 18 months, respectively, compared with 39% and 33% in the control group (P,0.001) (6). Similar remission rates were observed between groups in patients with major renal disease (75% complete remission in the rituximab group versus 76% in the CYC group).…”

An Unusual Case of Hematuria

“…In a subgroup analysis, RTX at 6 months was found to be superior to CYC in inducing remission in those who relapsed than CYC in patients enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial (39). Evaluation over a longer period of time of patients in the RAVE trial with severe AAV found that a single course of RTX was as effective as continuous conventional immunosuppressive therapy for induction and maintenance of remission over an 18-month period (44). RTX also has been used to maintain remission in noncontrolled trials, with promising results in an ongoing randomized controlled trial (40,42).…”