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?
Study Design and Methods
This retrospective study included 3524 patients (hematologic diseases=2500; 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=2523) and a prophylaxis group (n=1001) according to the administration of prophylactic TMP-SMX during the first 28 days 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). 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. Secondary outcome included the incidence of adverse drug reactions (ADRs) related to TMP-SMX.
Over 2759.9 person-years, 92 PJP infections occurred, with a mortality rate of 27.2%. The prophylaxis group showed a significantly lower incidence of PJP (adjusted sub-distribution hazard ratio (aSHR), 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 (aSHR, 0.01 [0.003–0.16]). The incidence of adverse drug reactions (ADRs) related to TMP-SMX was 18.1 (14.6–22.2)/100 person-years, and most were of mild-to-moderate severity. Based on ten 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.
Keywords : Pneumocystis jirovecii, rituximab, prophylaxis, trimethoprim-sulfamethoxazole