Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis

Ulrich Specks, Peter A. Merkel, Philip Seo, Robert Spiera, Carol A. Langford, Gary S. Hoffman, Cees G. M. Kallenberg, E. William St. Clair, Barri J. Fessler, Linna Ding, Lisa Viviano, Nadia K. Tchao, Deborah J. Phippard, Adam L. Asare, Noha Lim, David Ikle, Brett Jepson, Paul Brunetta, Nancy B. Allen, Fernando C. FervenzaDuvuru Geetha, Karina Keogh, Eugene Y. Kissin, Paul A. Monach, Tobias Peikert, Coen Stegeman, Steven R. Ytterberg, Mark Mueller, Lourdes P. Sejismundo, Kathleen Mieras, John H. Stone*, RAVE-ITN Res Grp

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

415 Citations (Scopus)

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

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, .)

Original languageEnglish
Pages (from-to)417-427
Number of pages11
JournalNew England Journal of Medicine
Volume369
Issue number5
DOIs
Publication statusPublished - 1-Aug-2013

Keywords

  • ANTIBODY-ASSOCIATED VASCULITIS
  • ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES
  • WEGENERS-GRANULOMATOSIS
  • RANDOMIZED-TRIAL
  • SYSTEMIC VASCULITIDES
  • RENAL VASCULITIS
  • CELL-ACTIVATION
  • CYCLOPHOSPHAMIDE
  • MAINTENANCE
  • RITUXIMAB

Cite this