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

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.