Is cotrimoxazole prophylaxis against Pneumocystis jirovecii pneumonia needed in patients with systemic autoimmune rheumatic diseases requiring immunosuppressive therapies?

Abstract

The incidence of Pneumocystis jirovecii pneumonia (PJP) has increased over recent years in patients with systemic autoimmune rheumatic diseases (SARD). PJP prognosis is poor in those receiving immunosuppressive therapy and glucocorticoids in particular. Despite the effectiveness of cotrimoxazole against PJP, the risk of adverse effects remains significant, and no consensus has emerged regarding the need for PJP prophylaxis in SARD patients undergoing immunosuppressor therapies.Objective:To evaluate the efficacy and safety of cotrimoxazole prophylaxis against PJP in SARD adult patients receiving immunosuppressive therapies. Methods: We performed a systematic review, consulting MEDLINE, EMBASE, and Cochrane Library databases up to April 2020. Outcomes covered prevention of PJP, other infections, morbidity, mortality, and safety. The information obtained was summarized with a narrative review and results were tabulated. Of the 318 identified references, 8 were included. Two were randomized controlled trials and six observational studies. The quality of studies was moderate or low. Despite disparities in the cotrimoxazole prophylaxis regimens described, results were consistent in terms of efficacy, particularly with glucocorticoid doses > 20mg/day. However, cotrimoxazole 400mg/80mg/day, prescribed three times/ week, or 200mg/40mg/day or in dose escalation, exhibited similar positive performances. Conversely, cotrimoxazole 400mg/80mg/day showed higher incidences of withdrawals and adverse effects. Cotrimoxazole prophylaxis against PJP exhibited efficacy in SARD, mainly in patients taking glucocorticoids ≥ 20mg/day. All cotrimoxazole regimens exposed seemed equally efficacious, although, higher quality trials are needed. Adverse effects were observed 2 months after initiation, particularly with the 400mg/80mg/day regimen. Conversely, escalation dosing or 200mg/40mg/day regimens appeared better tolerated.