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Comparative effectiveness of trimethoprim-sulfamethoxazole versus atovaquone for the prophylaxis of pneumocystis pneumonia in patients with connective tissue diseases receiving prolonged high-dose glucocorticoids

  • Observational Research
  • Published:
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Abstract

We compared the prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) with atovaquone for pneumocystis pneumonia (PCP) in patients with connective tissue diseases (CTDs) receiving high-dose glucocorticoids. Patients with CTDs aged ≥ 18 years who were treated with a prolonged course (≥ 4 weeks) of glucocorticoids (≥ 20 mg/day prednisone) in a Japanese tertiary center between 2013 and 2017 were included. The patients were categorized into two groups: TMP-SMX and atovaquone group. Adjusted cumulative incidence of PCP was compared between the two groups after propensity score weighting for differences in confounding factors. A total of 480 patients with a prolonged high-dose glucocorticoid treatment were identified. Out of 383 patients with TMP-SMX prophylaxis, 102 (26.8%) patients experienced adverse events leading to discontinuation within 4 weeks of initiation, while no patient in the atovaquone discontinued the therapy. Two hundred eighty-one patients received TMP-SMX, while 107 received atovaquone for PCP prophylaxis. During a total of 397.0 person-years, 7 PCP cases (2 in the TMP-SMX, 5 in the atovaquone) occurred with a mortality rate of 54.5%. After adjusting for differences in baseline characteristics, the adjusted cumulative incidence of PCP was similar between the two group (HR 0.97, 95% CI 0.19–5.09, p = 0.97). Prophylactic effects for PCP in CTDs patients receiving prolonged high-dose glucocorticoids were similar between TMP-SMX and atovaquone. Atovaquone was well-tolerated with no side effects.

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Data availability

The datasets generated and/or analyzed during the current study are not publicly available. Patients did not provide consent for raw data sharing during the data collection. All aggregated data relevant to the study are included in the article or uploaded as supplementary information.

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Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, University Graduate School of Medicine, 7-5-2 Kusunoki-chou, Kobe, Hyogo, 650-0017, Japan

    Sadao Jinno, Kengo Akashi, Yoko Nose, Mai Yamashita & Jun Saegusa

  2. Department of Advanced Medicine for Rheumatic Diseases, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Akira Onishi

Authors
  1. Sadao Jinno
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  2. Kengo Akashi
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  3. Akira Onishi
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  4. Yoko Nose
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  5. Mai Yamashita
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  6. Jun Saegusa
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Contributions

SJ, KA: conception and design of the work, analysis and interpretation of data, drafting the work, final approval of the version to be published and agreement to be accountable for all aspects of the work, AO: analysis and interpretation of data, drafting the work, final approval of the version to be published and agreement to be accountable for all aspects of the work, YN, MY, JS: acquisition of data, drafting the work, final approval of the version to be published and agreement to be accountable for all aspects of the work.

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Correspondence to Sadao Jinno.

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All authors have declared no conflicts of interests.

Ethics approval and consent to participate

This observational study was conducted as per the Declaration of Helsinki. The study was approved by the ethics committee of Kobe University (approval number B190296). In our institute, the institutional review board waived the requirement for patients’ informed consent, because this study utilized only existing data collected in clinical practice.

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Jinno, S., Akashi, K., Onishi, A. et al. Comparative effectiveness of trimethoprim-sulfamethoxazole versus atovaquone for the prophylaxis of pneumocystis pneumonia in patients with connective tissue diseases receiving prolonged high-dose glucocorticoids. Rheumatol Int 42, 1403–1409 (2022). https://doi.org/10.1007/s00296-021-04945-w

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  • DOI: https://doi.org/10.1007/s00296-021-04945-w

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