Prophylaxis against pneumocystis pneumonia in rheumatoid arthritis patients treated with b/tsDMARDs: insights from 3787 cases in the FIRST registry

Abstract

Abstract Objectives The use of biologic and targeted synthetic (b/ts) DMARDs in the treatment of RA is increasing. Therefore, prevention of b/tsDMARDs-induced infection is important. Here we describe a prophylaxis protocol for preventing pneumocystis pneumonia (PCP) in RA patients treated with b/tsDMARDs. Methods The study subjects were 3787 RA patients from the FIRST registry. They were divided into cohort 1 (n = 807, requiring prophylaxis against PCP based on physicians’ assessment at the point of new treatment with or switch to b/tsDMARDs) and cohort 2 (n = 2980, receiving strategic PCP prophylaxis). The incidence and risk factors for PCP were investigated. Results Twenty-six PCP cases were observed throughout the study. After the introduction of strategic PCP prophylaxis, PCP incidence diminished from 0.51/100 person-years (PYs) to 0.21/100 PYs (risk ratio = 0.42). Sulfamethoxazole and trimethoprim in combination (SMX–TMP) showed greater efficacy in the prevention of PCP than pentamidine inhalation (P <0.0001). The prophylaxis rate increased chronologically despite the falls in the average SMX–TMP dose and in the incidence of PCP. Subanalysis of the data for 929 patients from both groups who did not receive prophylaxis showed that old age, high BMI, coexisting lung diseases, low lymphocyte count, and low serum IgG levels increased the risk of PCP development. Development of PCP could be predicted (using an equation based on these variables) in patients not treated with glucocorticoids [area under the curve (AUC) = 0.910)], but less accurately in those on glucocorticoids (AUC = 0.746). Conclusions Our study clarified the risk factors for PCP in RA patients on b/tsDMARDs treatment and highlighted and defined the criteria for effective prophylaxis against PCP.