Risk–Benefit Analysis of Primary Prophylaxis Against Pneumocystis Jirovecii Pneumonia in Patients With Rheumatic Diseases Receiving Rituximab

Abstract

ObjectiveTo identify a specific population of patients with rheumatic diseases receiving rituximab treatment for whom the benefit from primary prophylaxis against Pneumocystis jirovecii pneumonia (PJP) outweighs the risk of adverse events (AEs)MethodsThis study included 818 patients treated with rituximab for rheumatic diseases. Of these, 419 received prophylactic trimethoprim‐sulfamethoxazole (TMP‐SMX) with rituximab while the remainder did not. Differences in 1‐year PJP incidence between the groups were estimated using Cox regression. Risk‐benefit assessment was performed in the subgroup stratified according to risk factors based on the number needed to treat (NNT) to prevent one case of PJP and the number needed to harm (NNH) due to severe AEs. Inverse probability of treatment weighting was applied to minimize the confounding by indication.ResultsDuring the 663.1 person‐years, there were 11 PJP cases, with a mortality rate of 63.6%. Concomitant use of high‐dose glucocorticoids (≥30mg/day of prednisone during 4 weeks after rituximab administration) was the most important risk factor. The PJP incidence (per 100 person‐years) was 7.93 (2.91–17.25) in the subgroup receiving high‐dose glucocorticoids, compared with 0.40 (0.01–2.25) in the subgroup without high‐dose glucocorticoids. Although prophylactic TMP‐SMX significantly reduced the overall PJP incidence (HR 0.11 [0.03–0.37]), the NNT to prevent one PJP was higher than the NNH (146 vs. 86). In contrast, the NNT fell to 20 (10.7–65.7) in patients receiving concomitant high‐dose glucocorticoids.ConclusionThe benefit associated with primary PJP prophylaxis overweighs the risk of severe AEs in patients receiving rituximab and concomitant high‐dose glucocorticoid treatment.This article is protected by copyright. All rights reserved.image

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