Background Pneumocystis pneumonia (PCP) is a serious and potentially fatal complication observed in 0.1-0.4% of Japanese patients with rheumatoid arthritis (RA) receiving biological agents during the first 6 months. Although the preventive administration of trimethoprim/sulfamethoxasole (TMP/SMX) has been recommended for high-risk patients, the intolerability due to various adverse events highly limits the prophylactic prescription of TMP/SMX in daily clinical practice. Recently, an increased immune response by cell wall β-D-glucan through nuclear factor kappa B (NF-kB) and its inhibition by salazosulfapyridine (SASP) have been reported as for the pathophysiology of PCP.
Objectives We investigated the possible preventive effect of SASP on the development of PCP in Japanese patients with RA receiving methotrexate (MTX) with or without biological agents.
Methods This retrospective study comprised of 216 RA patients followed up at Toho University Ohashi Medical Center between January 2005 and October 2013. Patients who had never received MTX and those received preventive TMP/SMX were excluded from the study. The diagnosis of PCP was defined by the presence of acute bilateral infiltration observed on the chest high-resolution computed tomography (HRCT) images and either positive polymerase chain reaction (PCR) for Pneumocystis jirovecii, or an elevated (>20 pg/mL) serum β-D-glucan level, and a compatible clinical course.
Results Among 216 RA patients, 61 patients were continuously receiving SASP, and those patients were significantly older than those without SASP (69.6 versus 63.5 years; p=0.003). Other demographic features including gender and MTX dose were comparable between SASP (+) and SASP (−) patients. Notably, PCP never developed in SASP (+) patients, while PCP eventually developed in 11 of 155 (7.1%) SASP (−) patients (p=0.036 by Fisher's exact test).
Conclusions Our findings support the preventive effect of SASP on the development of PCP in patients with RA, and those results should be confirmed by larger cohorts and a future randomized controlled study.
Wang J, Gigliotti F, Bhagwat SP, et al. Immune modulation with sulfasalazine attenuates immunopathogenesis but enhances macrophage-mediated fungal clearance during Pneumocystis pneumonia. PLoS Pathog 2010.
Disclosure of Interest : None declared