FRI0529 IS COTRIMOXAZOLE PROPHYLAXIS AGAINST PNEUMOCISTIS JIROVENCII PNEUMONIA RECOMMENDED IN PATIENTS WITH SYSTEMIC AUTOIMMUNE DISEASES REQUIRING IMMUNOSUPPRESSIVE THERAPIES? A SYSTEMATIC LITERATURE REVIEW.
Authors: C. A. Pereda Testa, M. B. Nishishinya, P. Díaz del Campo Fontecha, N. Brito-García
Journal: Annals of the Rheumatic Diseases (2020)

Background: The incidence of Pneumocistis jirovencii pneumonia (PCP) has increased substantially during the past years in patients with systemic autoimmune diseases (SAD). Mortality associated to PCP was reported to be up to 20 to 58%, particularly in those receiving immunosuppressive therapy, such as tumoral necrosis antagonist factors or glucocorticoid therapy. Though, there is clear evidence of the effectiveness of Cotrimoxazole against PCP, the risk of adverse effects is important, increasing morbidity and mortality. Up to date, there is no consensus about the need of PCP prophylaxis in SAD patients with immunosuppressed therapies. Objectives: To analyse the efficacy and safety of Cotrimoxazole prophylaxis against PCP in SAD adult patients receiving immunosuppressive therapies. Methods: We performed a comprehensive literature search, screening different databases, MEDLINE, EMBASE and Cochrane Library up to April 2019. Outcomes covered prevention of PCP or other infections, morbidity, mortality and safety. All categories of studies were included. Two reviewers selected and extracted data from studies. The information obtained was summarized through a narrative review and results tabulated. Results: From the initial 340 identified references, 12 were finally included. Two were randomized controlled trials, six observational studies, and four case reports. The quality in the majority of studies resulted moderate or low, with limited level of evidence. Besides, all Cotrimoxazole prophylaxis regimens described in each study were distinct. Results were consistent to exhibit the efficacy of Cotrimoxazole prophylaxis, compared to non-prophylaxis in the prevention of PCP in patients receiving immunosupresor therapy, particularly, those taking high glucocorticoid dose above 20mg/day. In terms of efficacy, Cotrimoxazole 400mg/80mg/day, given three times per week, or 200mg/40mg/day or in dose escale exhibited a similar performance. In contrast, Cotrimoxazole 400mg/80mg/day displayed a higher incidence of adverse effects. Conclusion: Cotrimoxazole prophylaxis against PCP exhibited efficacy compared to non-prophylaxis, mainly in patients treated with high dose of glucocorticoids (≥20mg/day), causing a significant reduction in mortality. Positive efficacy results did not differ despite the diverse Cotrimoxazol regimens exposed. However, Cotrimoxazole adverse effects were observed after two months from initiation; particularly with daily dose of 400mg/80mg. In contrast, escalate dose or 200mg/40mg/day dose regimens appeared better tolerated. **This review is part of the Spanish Rheumatology Society –SER- recommendations on Systemic Autoimmune Diseases. References: [1] Utsunomiya, M., et al. (2017). “Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: results from a non-blinded, randomized controlled trial.” Arthritis Res Ther 19(1): 7. [2] Yamamoto, T., et al. (2014). “A feasibility study assessing tolerability of daily versus twice weekly trimethoprim-sulfamethoxazole regimen for prophylaxis against pneumocystis pneumonia in patients with systemic autoimmune diseases on glucocorticoid therapy.” Japanese Journal of Clinical Pharmacology and Therapeutics 45(3): 89-92. Disclosure of Interests: None declared