Trimethoprim sulfamethoxazole prophylaxis and serious infections in granulomatosis with polyangiitis treated with rituximab

Abstract Objective To assess the association of trimethoprim sulfamethoxazole (TMP-SMX) prophylaxis with serious infections in rituximab-treated patients with granulomatosis with polyangiitis (GPA). Methods This retrospective cohort study included adults with GPA (2011–2020) within the United States Merative™ Marketscan® Research Databases with ≥6 months’ enrolment prior to first (index) rituximab treatment. We defined TMP-SMX prophylaxis as a ≥28-day prescription dispensed after or overlapping the index date. Serious infection was a hospital primary diagnosis for infection (excluding viral or mycobacterial codes). Secondary outcomes were outpatient infection, Pneumocystis jirovecii pneumonia (PJP) and adverse events potentially attributable to TMP-SMX. Cox proportional hazards regression assessed the association of time-varying TMP-SMX with outcomes of interest, adjusting for potential confounders. Individuals were followed until the outcome of interest, end of database enrolment or 31 Decamber 2020. Results Among 919 rituximab-treated individuals (53% female), mean (s.d.) age was 52.1 (16) years and 281 (31%) were dispensed TMP-SMX within 30 days of index date. Over a median of 496 (interquartile range 138–979) days, 130 serious infections occurred among 104 individuals (incidence 6.1 95% CI: 5.0, 7.4 per 100 person-years). Time-varying TMP-SMX was negatively associated with serious infection (adjusted hazard ratio aHR 0.5; 95% CI: 0.3, 0.9). The aHR for outpatient infections was 0.8 (95% CI: 0.6, 1.1). The estimate for PJP was imprecise (13 events, unadjusted HR 0.2; 95% CI: 0.03–1.8). TMP-SMX was potentially associated with adverse events (aHR 1.3; 95% CI: 0.9, 1.9). Conclusions TMP-SMX prophylaxis was associated with reduced serious infections in rituximab-treated GPA, but may increase adverse events, warranting further study of optimal prophylaxis strategies.