Rituximab for remission induction and maintenance in refractory granulomatosis with polyangiitis (Wegener's): ten-year experience at a single center

Arthritis Rheum. 2012 Nov;64(11):3770-8. doi: 10.1002/art.34584.

Abstract

Objective: This study was conducted to evaluate the efficacy and safety of repeated and prolonged B cell depletion with rituximab (RTX) for the maintenance of long-term remission in patients with chronic relapsing granulomatosis with polyangiitis (Wegener's) (GPA).

Methods: We conducted a single-center observational study of all patients with chronic relapsing GPA treated with at least 2 courses of RTX between January 1, 2000 and May 31, 2010. Participants in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were excluded from this analysis. Data were abstracted from electronic medical records.

Results: Fifty-three patients with refractory GPA (median age 46 years [interquartile range (IQR) 30-61 years]; 53% women) received at least 2 courses of RTX to treat GPA relapses or to maintain remission. All but 1 patient had antineutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3). These patients received a median of 4 courses of RTX (IQR 3-5); all had depletion of B cells, and the median time to return of B cells was 8.5 months (IQR 6-11 months). All observed relapses occurred after reconstitution of B cells and were accompanied or preceded by an increase in ANCA levels, except for the 1 ANCA-negative patient. Infusion-related adverse events occurred in 16 patients. During the period of B cell depletion, 30 infections requiring antimicrobial therapy were recorded.

Conclusion: RTX appeared to be effective and safe for the induction and maintenance of remission in patients with chronic relapsing GPA. Repeated depletion of B lymphocytes seems to be associated with a low risk of infections. Preemptive re-treatment decisions can be individualized based on serial B lymphocyte and PR3 ANCA monitoring. The use of RTX for the maintenance of long-term remission merits further formal investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage*
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Glucocorticoids / administration & dosage
  • Granulomatosis with Polyangiitis / drug therapy*
  • Granulomatosis with Polyangiitis / immunology
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / adverse effects
  • Male
  • Middle Aged
  • Remission Induction
  • Rituximab
  • Secondary Prevention
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Glucocorticoids
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunologic Factors
  • Rituximab