Trimethoprim-sulfamethoxazole prophylaxis prevents severe/life-threatening infections following rituximab in antineutrophil cytoplasm antibody-associated vasculitis

Ann Rheum Dis. 2018 Oct;77(10):1440-1447. doi: 10.1136/annrheumdis-2017-212861. Epub 2018 Jun 27.

Abstract

Objective: We aimed to assess risk factors for the development of severe infection in patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV) receiving rituximab.

Methods: 192 patients with AAV were identified. Univariate and multivariate analyses were performed to identify risk factors for severe infection following rituximab. Severe infections were classified as grade ≥3 as proposed by the Common Terminology Criteria for Adverse Events V.4.0.

Results: 95 severe infections were recorded in 49 (25.52%) patients, corresponding to an event rate of 26.06 per 100 person-years. The prophylactic use of trimethoprim-sulfamethoxazole was associated with a lower frequency of severe infections (HR 0.30, 95% CI 0.13 to 0.69), while older age (HR 1.03, 95% CI 1.01 to 1.05), endobronchial involvement (HR 2.21, 95% CI 1.14 to 4.26), presence of chronic obstructive pulmonary disease (HR 6.30, 95% CI 1.08 to 36.75) and previous alemtuzumab use (HR 3.97, 95% CI 1.50 to 10.54) increased the risk. When analysis was restricted to respiratory tract infections (66.3% of all infections), endobronchial involvement (HR 4.27, 95% CI 1.81 to 10.06), severe bronchiectasis (HR 6.14, 95% CI 1.18 to 31.91), higher neutrophil count (HR 1.19, 95% CI 1.06 to 1.33) and major relapse (HR 3.07, 95% CI 1.30 to 7.23) as indication for rituximab use conferred a higher risk, while refractory disease (HR 0.25, 95% CI 0.07 to 0.90) as indication had a lower frequency of severe infections.

Conclusions: We found severe infections in one quarter of patients with AAV receiving rituximab. Trimethoprim-sulfamethoxazole prophylaxis reduced the risk, while especially bronchiectasis and endobronchial involvement are risk factors for severe respiratory infections.

Keywords: ANCA; infections; rituximab; trimethoprim-sulfamethoxazole; vasculitis.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / drug therapy*
  • Antibiotic Prophylaxis / methods*
  • Female
  • Humans
  • Immunologic Factors / adverse effects*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Respiratory Tract Infections / chemically induced
  • Respiratory Tract Infections / prevention & control*
  • Risk Factors
  • Rituximab / adverse effects*
  • Treatment Outcome
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use*
  • Young Adult

Substances

  • Immunologic Factors
  • Rituximab
  • Trimethoprim, Sulfamethoxazole Drug Combination