Sulfasalazine May Be Preventive Against Pneumocystis Pneumonia in RA

The preventive efficacy of sulfasalazine against Pneumocystis pneumonia was demonstrated among patients with RA.

The preventive effect of sulfasalazine against the prevention of Pneumocystis pneumonia (PCP) was demonstrated in patients with rheumatoid arthritis (RA), in a retrospective study published in Journal of Infection and Chemotherapy.

Pneumocystis pneumonia is an opportunistic lung infection that has been reported among individuals with RA, with an animal study showing that sulfasalazine enhances the clearance of Pneumocystis from the lungs via the acceleration of macrophage activity.

A self-controlled case series technique was used to evaluate the association between use of sulfasalazine and development of PCP in patients with RA.

The researchers explored all episodes of PCP that had developed among patients with RA at 5 hospitals in Japan between 2003 and 2019. PCP was defined according to the following criteria: detection of Pneumocystis jirovecii in respiratory tract specimens by polymerase chain reaction (PCR); clinical symptoms, including drug cough, dyspnea, hypoxia, or pyrexia; diffuse interstitial infiltrate on chest imaging; and the absence of any PCP prophylaxis.

This finding may help promote sulfasalazine as another option in the prevention of PCP in patients with RA.

A total of 49 patients were enrolled in the current analysis. All participants experienced 1 episode of PCP, with 1 of them experiencing 2 episodes, thus resulting in a total of 50 episodes of PCP. Overall, 30 participants received sulfasalazine at some point during their observation. Researchers noted that 49 episodes of PCP developed in 170.3 person-years without sulfasalazine use and only 1 episode of PCP developed in 103.7 person-years with sulfasalazine use.

In the age-adjusted model, sulfasalazine use was associated with a decreased risk for PCP (IRR, 0.01; 95% CI, <0.01-0.05), whereas use of prednisolone of more than 5 mg/day or an equivalent corticosteroid dose (IRR, 4.99; 95% CI, 1.52-17.64) and tumor necrosis factor (TNF) inhibitor use (IRR, 9.73; 95% CI, 2.24-55.3) were significantly associated with an increased risk for PCP.

Treatment with sulfasalazine was associated with a decreased risk for development of PCP (adjusted IRR, <0.01; 95% CI, <0.01-0.03), following adjustments for age, as well as for the administration of glucocorticoids, methotrexate, and TNF inhibitors.

Limitations included the study design, the preclusion of occurrence of any subsequent events because 17 patients died from PCP, and the small sample size, which may have led to an inaccurate estimate of the preventive efficacy of sulfasalazine.

The study authors concluded that the findings from this study “…may help promote sulfasalazine as another option in the prevention of PCP in patients with RA.”


Nunokawa T, Chinen N, Shimada K, et al. Efficacy of sulfasalazine for the prevention of Pneumocystis pneumonia in patients with rheumatoid arthritis: a multicentric self-controlled case series study. J Infect Chemother. Published online November 5, 2022. doi:10.1016/j.jiac.2022.10.019