Effectiveness and safety of lower dose sulfamethoxazole/trimethoprim for Pneumocystis jirovecii pneumonia prophylaxis in patients with systemic rheumatic diseases receiving moderate-to high-dose glucocorticoids

Objectives: To compare the effectiveness and safety of low-dose sulfamethoxazole/trimethoprim (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in patients with systemic rheumatic disease (SRD) who were receiving glucocorticoids. Methods: We retrospectively analyzed data obtained from Japanese patients with SRD who received glucocorticoids between January 2006 and April 2024. Patients were divided into two groups based on the initial dose of SMX/TMP: low-dose (one tablet twice weekly on non-consecutive days); conventional-dose (one tablet per day). The primary endpoint was the incidence of PCP after 1 year since the initiation of SMX/TMP. Secondary endpoints were discontinuation rates of SMX/TMP therapy and severe adverse drug reactions (ADRs) after 1 year since the initiation of SMX/TMP in both groups, before and after adjusting for patient characteristics. Results: A total of 186 patients were included in this study: 60 in the low-dose group and 126 in the conventionaldose group. No patients developed PCP within one year after starting SMX/TMP; however, two patients in the low-dose group required escalation of the SMX/TMP dose to the conventional dose due to subclinical PCP. In the adjusted analysis, the low-dose group had a significantly lower discontinuation rate and a lower incidence rate of severe ADRs than the conventional-dose group. Conclusions: Lower-dose SMX/TMP therapy was as effective as conventional therapy for PCP prophylaxis and was associated with lower discontinuation rates in patients with SRD receiving glucocorticoids.