A single cycle of rituximab for the treatment of severe pemphigus

N Engl J Med. 2007 Aug 9;357(6):545-52. doi: 10.1056/NEJMoa067752.

Abstract

Background: The combination of multiple cycles of rituximab and intravenous immune globulins has been reported to be effective in patients with severe pemphigus. The aim of this study was to assess the efficacy of a single cycle of rituximab in severe types of pemphigus.

Methods: We studied 21 patients with pemphigus whose disease had not responded to an 8-week course of 1.5 mg of prednisone per kilogram of body weight per day (corticosteroid-refractory disease), who had had at least two relapses despite doses of prednisone higher than 20 mg per day (corticosteroid-dependent disease), or who had severe contraindications to corticosteroids. The patients were treated with four weekly infusions of 375 mg of rituximab per square meter of body-surface area. The primary end point was complete remission 3 months after the end of rituximab treatment; complete remission was defined as epithelialization of all skin and mucosal lesions.

Results: Eighteen of 21 patients (86%; 95% confidence interval, 64 to 97%) had a complete remission at 3 months. The disease relapsed in nine patients after a mean of 18.9+/-7.9 months. After a median follow-up of 34 months, 18 patients (86%) were free of disease, including 8 who were not receiving corticosteroids; the mean prednisone dose decreased from 94.0+/-10.2 to 12.0+/-7.5 mg per day (P=0.04) in patients with corticosteroid-refractory disease and from 29.1+/-12.4 to 10.9+/-16.5 mg per day (P=0.007) in patients with corticosteroid-dependent disease. Pyelonephritis developed in one patient 12 months after rituximab treatment, and one patient died of septicemia 18 months after rituximab treatment. These patients had a profound decrease in the number of circulating B lymphocytes but normal serum levels of IgG.

Conclusions: A single cycle of rituximab is an effective treatment for pemphigus. Because of its potentially severe side effects, its use should be limited to the most severe types of the disease. (ClinicalTrials.gov number, NCT00213512 [ClinicalTrials.gov].).

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents / administration & dosage
  • Antibodies / blood
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Murine-Derived
  • B-Lymphocytes
  • Desmogleins / immunology
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin Isotypes / blood
  • Immunologic Factors / administration & dosage*
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Pemphigus / drug therapy*
  • Pemphigus / immunology
  • Prednisone / administration & dosage
  • Remission Induction
  • Rituximab

Substances

  • Anti-Inflammatory Agents
  • Antibodies
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Desmogleins
  • Immunoglobulin Isotypes
  • Immunologic Factors
  • Rituximab
  • Prednisone

Associated data

  • ClinicalTrials.gov/NCT00213512