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Clinical effectiveness and safety of leflunomide in inflammatory arthritis: a report from the RAPPORT database with supporting patient survey

Clinical Rheumatology volume 36, pages 1471–1478 (2017)Cite this article

Abstract

Leflunomide is indicated for the treatment of adults with rheumatoid arthritis, yet is underutilized. Given the cost of biologic therapy, understanding real-life effectiveness, safety, and sustainability of leflunomide, particularly in patients who have failed methotrexate, would be of value. The primary objective was to assess the proportion of patients achieving clinically meaningful benefit following an adequate trial of leflunomide. A retrospective analysis of a cohort supplemented with patient self-reported data using a standardized questionnaire. Data were analyzed using descriptive statistics, with a database multivariate logistic regression analysis to determine predictors of leflunomide response. Of the cohort available (N = 2591), 1671 patients with confirmed leflunomide use were included in the retrospective analysis, of whom 249 were incident users. Low disease activity (DAS-28 < 3.2) was achieved or maintained by 20% of incident users, with 19% achieving a clinical response (DAS-28 decrease ≥1.2) at 3 months. Adverse effects (AE) were reported by 29% of incident users and after 1 year, 45% remained on leflunomide. Achievement of “minimal or no joint symptoms” was reported by 34% in the 661 analyzable survey responses (39% response rate). AE were reported by 55%, with nuisance (hair loss, nausea, stomach pain) AE and diarrhea being most common. Leflunomide was discontinued by 67% of responders within 1 year. An important proportion of patients, the majority of whom had previously failed methotrexate, achieved disease response with leflunomide with a low risk of serious adverse effects, suggesting that a trial of leflunomide may be a reasonable and cost-effective strategy prior to biologic therapy.

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Author information

Affiliations

  1. Misericordia Hospital, Covenant Health, 16940 87Ave, Edmonton, AB, T5R 4H5, Canada

    Morgan Schultz

  2. Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, 8-130K Clinical Sciences Building, 11350 83 Ave, Edmonton, AB, T5G 2G3, Canada

    Stephanie O. Keeling, Steven J. Katz & Walter P. Maksymowych

  3. School of Public Health, University of Alberta, 2-040 Li Ka Shing Centre for Health Research Institute, Edmonton, AB, T6G 2E1, Canada

    Dean T. Eurich

  4. Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, 3-171 Edmonton Clinic Health Academy, 11405-87Ave, Edmonton, Alberta, T6G 1C9, Canada

    Jill J. Hall

Authors
  1. Morgan Schultz
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  2. Stephanie O. Keeling
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  3. Steven J. Katz
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  4. Walter P. Maksymowych
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  5. Dean T. Eurich
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  6. Jill J. Hall
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Corresponding author

Correspondence to Jill J. Hall.

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Ethical standards

This study was approved by the Research Ethics Board at the University of Alberta and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All patients provided their informed consent to participate in the RAPPORT study and by completing the survey tool.

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Schultz, M., Keeling, S.O., Katz, S.J. et al. Clinical effectiveness and safety of leflunomide in inflammatory arthritis: a report from the RAPPORT database with supporting patient survey. Clin Rheumatol 36, 1471–1478 (2017). https://doi.org/10.1007/s10067-017-3687-5

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  • DOI: https://doi.org/10.1007/s10067-017-3687-5

Keywords

  • Drug safety
  • Leflunomide
  • Pharmacovigilance
  • Rheumatoid arthritis
  • Self-report