Risk of infections in patients with pemphigus treated with rituximab vs. azathioprine or mycophenolate mofetil: a large-scale global cohort study

Khalaf Kridin*, Noor Mruwat, Kyle T. Amber, Ralf J. Ludwig

*Corresponding author for this work
6 Citations (Scopus)

Abstract

Background: The risk of infectious complications among patients with pemphigus managed by rituximab is yet to be precisely elucidated. Objectives: To evaluate the risk of infections in patients with pemphigus managed by rituximab vs. first-line corticosteroid-sparing agents [azathioprine and mycophenolate mofetil (MMF)]. Methods: A global population-based cohort study compared patients with pemphigus initiating rituximab (n = 963) vs. azathioprine or MMF (n = 963) regarding the risk of 26 different infections. Propensity score matching was conducted to optimize comparability. Results: During the initial 12 months following treatment, patients under rituximab experienced elevated risk of COVID-19 [hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.06-3.14; P = 0.028], parasitic diseases (HR 3.22, 95% CI 1.04-9.97; P = 0.032) and cytomegalovirus (CMV) infection (HR 1.63, 95% CI 1.04-2.58; P = 0.033). When evaluating infections developing ≥ 12 months after drug initiation, rituximab was associated with greater risk of pneumonia (HR 1.45, 95% CI 1.00-2.10; P = 0.047), COVID-19 (HR 1.87, 95% CI 1.49-2.33; P < 0.001), osteomyelitis (HR 2.42, 95% CI 1.11-5.31; P = 0.023), herpes simplex virus (HR 2.06, 95% CI 1.03-4.11; P = 0.037) and CMV (HR 1.63, 95% CI 1.07-2.49; P = 0.023) infections. Conclusions: Within the first 12 months after treatment, patients under rituximab experience an elevated risk of COVID-19, parasitic and CMV infections. Rituximab is associated with pneumonia, osteomyelitis and viral diseases even beyond the first year after therapy. Pneumococcal vaccine and suppressive antiviral therapy should be considered even 1 year following therapy. There is no signal for elevated risk of tuberculosis, hepatitis B virus reactivation, Pneumocystis jiroveci pneumonia and progressive multifocal leukoencephalopathy.

Original languageEnglish
JournalBritish Journal of Dermatology
Volume188
Issue number4
Pages (from-to)499-505
Number of pages7
ISSN0007-0963
DOIs
Publication statusPublished - 04.2023

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

  • 205-19 Dermatology
  • 204-05 Immunology
  • 205-22 Clinical Immunology and Allergology

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