Primary Prophylaxis for Pneumocystis jirovecii Pneumonia in Patients Receiving Rituximab

Abstract

Although previous studies suggested that rituximab increases the risk of Pneumocystis jirovecii pneumonia (PJP), it is uncertain whether its primary prophylaxis for PJP is justified. Does the benefit of primary prophylaxis for PJP in patients receiving rituximab treatment outweigh the potential risk of the prophylaxis? This retrospective study included 3,524 patients (hematologic diseases, 2,500; rheumatic diseases, 559; pre/post-solid organ transplantation, 465) first exposed to rituximab between 2002 and 2018 in a tertiary referral center in South Korea. Patients were classified into a control group (n= 2,523) and a prophylaxis group (n= 1,001) according to the administration of prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) during the first 28days after the start of rituximab (intention-to-treat analysis). In addition, exposure to TMP-SMX was examined as a time-varying variable (time-varying analysis). The primary outcome was the prophylactic effect of TMP-SMX on the 1-year incidence of PJP. Inverse probability of treatment weights was applied to minimize the baseline imbalance. The secondary outcome included the incidence of adverse drug reactions (ADRs) related to TMP-SMX. Over 2,759.9 person-years, 92 PJP infections occurred, with a mortality rate of 27.2%. The prophylaxis group showed a significantly lower incidence of PJP (adjusted subdistribution hazard ratio, 0.20 [95%CI, 0.10-0.42]) than the control group. This result was consistent with the results of time-varying analysis, in which only one PJP infection occurred during TMP-SMX administration (adjusted subdistribution hazard ratio, 0.01 [0.003-0.16]). The incidence of ADRs related to TMP-SMX was 18.1 (14.6-22.2)/100 person-years, and most were of mild to moderate severity. On the basis of 10 severe ADRs, the number needed to harm was 101 (61.9-261.1), whereas the number needed to prevent one PJP infection was 32 (24.8-39.4). TMP-SMX prophylaxis significantly reduces PJP incidence with a tolerable safety profile in patients receiving rituximab treatment.