Sulfasalazine as a Prophylactic for Pneumocystis Pneumonia in Patients With Rheumatoid Arthritis: A Cohort Study

We investigated the potential of sulfasalazine (SSZ), one of the conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis (RA).

In this longitudinal cohort study, we enrolled patients with RA who started receiving new RA treatment. A treatment episode was defined as a period of 1 year from the start or increase of DMARDs dose, or starting prednisolone > 10 mg/day, and the incidence of PCP in this period was assessed. All treatment episodes were classified into two groups based on the presence of SSZ at baseline. The PCP incidence rate in the two groups was evaluated using a negative binomial regression model.

A total of 848 treatment episodes were recorded in 594 RA patients: 181 and 667 in the SSZ and control groups, respectively. During the 850.6 person-years of observation, 21 patients developed PCP, and three died of PCP. Multivariable adjusted analysis using Firth's method showed that the 1-year incidence of PCP was significantly reduced with SSZ treatment (p = 0.003, rate ratio = 0.05; 95% CI 0.00-0.34). Furthermore, the log-rank test in the propensity score-matched population confirmed this result. Regarding safety, 45 adverse drug reactions related to SSZ occurred (4.34/100 person-years; 95% CI 3.26-5.78). Only one serious adverse reaction (drug-induced hypersensitivity syndrome) was observed, which resolved after discontinuation of SSZ.

We demonstrated the preventive efficacy of SSZ on PCP. The pleiotropic effect of this traditional DMARD may impact RA treatment, providing another option for PCP prophylaxis.