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

BACKGROUND: The risk of infectious complications among patients with pemphigus managed by rituximab is yet to be precisely elucidated.

OBJECTIVE: To evaluate the risk of infections in patients with pemphigus managed by rituximab versus first-line corticosteroid-sparing agents (azathioprine and mycophenolate mofetil [MMF]).

METHODS: A global population-based cohort study compared pemphigus patients initiating rituximab (n = 963) versus azathioprine or MMF (n = 963) regarding the risk of 26 different infections. Propensity score matching was conducted to optimize comparability.

RESULTS: In 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 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 (HR, 2.06; 95% CI, 1.03-4.11; P = 0.037), and cytomegalovirus (HR, 1.63; 95% CI, 1.07-2.49; P = 0.023) infections.

CONCLUSION: 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 one year following therapy. No signal for elevated risk of tuberculosis, hepatitis B virus reactivation, pneumocystis jiroveci pneumonia, and progressive multifocal leukoencephalopathy.