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Extended report
Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids
  1. Jun Won Park1,
  2. Jeffrey R Curtis2,
  3. Jinyoung Moon1,
  4. Yeong Wook Song1,
  5. Suhnggwon Kim3,4,
  6. Eun Bong Lee1
  1. 1 Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
  2. 2 Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA
  3. 3 Division of Nephrology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
  4. 4 Seoul Kidney Clinic, Seoul, Republic of Korea
  1. Correspondence to Dr Eun Bong Lee, Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea; leb7616{at}


Objectives To investigate the efficacy and safety of trimethoprim/sulfamethoxazole (TMP-SMX) as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatic diseases receiving high-dose steroids.

Methods The study included 1522 treatment episodes with prolonged (≥4 weeks) high-dose (≥30 mg/day prednisone) steroids in 1092 patients over a 12-year period. Of these, 262 treatment episodes involved TMP-SMX (prophylaxis group) while other episodes involved no prophylaxis (control group). Differences in 1-year PCP incidence and its mortality between the two groups were estimated using Cox regression. To minimise baseline imbalance, propensity score matching was performed and efficacy outcome was mainly assessed in the postmatched population (n=235 in both groups).

Results During a total of 1474.4 person-years, 30 PCP cases occurred with a mortality rate of 36.7%. One non-fatal case occurred in the prophylaxis group. TMP-SMX significantly reduced the 1-year PCP incidence (adjusted HR=0.07(95% CI 0.01 to 0.53)) and related mortality (adjusted HR=0.08 (95% CI 0.0006 to 0.71)) in the postmatched population. The result of the same analysis performed in the whole population was consistent with that of the primary analysis. Incidence rate of adverse drug reactions (ADR) related to TMP-SMX was 21.2 (14.8–29.3)/100 person-years. Only two serious ADRs (including one Stevens-Johnson syndrome case) occurred. The number needed to treat for preventing one PCP (52 (33–124)) was lower than the number needed to harm for serious ADR (131 (55–∞)).

Conclusion TMP-SMX prophylaxis significantly reduces the PCP incidence with a favourable safety profile in patients with rheumatic disease receiving prolonged, high-dose steroids.

  • corticosteroids
  • infections
  • autoimmune diseases
  • epidemiology
  • outcomes research

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  • Handling editor Tore K Kvien

  • Contributors EBL had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: EBL, JRC, SK and JWP. Acquisition, analysis or interpretation of data: JWP, JRC, JM, YWS and EBL. Drafting of the manuscript: EBL, JRC and JWP. Critical revision of the manuscript for important intellectual content: JWP, JRC, JM, YWS, SK and EBL. Statistical analysis: EBL, JRC and JWP.

  • Funding This research was partly supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2016R1D1A1A02937044).

  • Competing interests EBL has acted as a consultant to Pfizer, and received research grants from Green Cross Corp and Hanmi Pharm Company. The other authors declare no conflicts of interest.

  • Patient consent Informed consents were waived based on the retrospective nature of the study.

  • Ethics approval The study was approved by the Institutional Review Board of the Seoul National University Hospital (IRB 1508-050-694) and was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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