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Short-Term Efficacy and Safety of Leflunomide in the Treatment of Active Rheumatoid Arthritis in Everyday Clinical Use

Open-Label, Prospective Study

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Abstract

Objective: To determine the efficacy and safety profile of 6-month treatment with leflunomide 20mg daily in patients with acute rheumatoid arthritis (RA) receiving treatment from 197 office-based rheumatologists in France.

Methods: This open-label, prospective, multicentre study included 378 ambulatory RA patients who received leflunomide at a loading dose of 100mg daily on days 1–3, followed by 20mg daily for 6 months. The primary efficacy endpoint was a >20% response according to the American College of Rheumatology criteria (ACR 20) after 6 months. Secondary efficacy criteria were a ≥50% response (ACR 50) and a ≥70% response (ACR 70), as well as disease activity score (DAS28) responses.

Results: Among the 407 selected patients, 378 patients were included in the study, all of whom were treated with leflunomide. Female patients made up 78.6% of the study population; the mean age was 57.7 ± 12.0 years, and the mean disease duration was 9.7 ± 8.5 years. At 6 months, the ACR 20 response rate was 48.2% (95% confidence interval [CI] 43–53%). ACR 50 and 70 response rates were 25.3% (95% CI 21.0–30.1) and 11.7% (95% CI 8.6–15.4%), respectively. According to the DAS28, 21.8% of patients had a good response, 39.9% a moderate response, and 38.2% were non-responders. The DAS28 response rate was thus 61.8% (95% CI 56.5–66.9%). Mean improvements in tender joint count were -5.6 ± 7.4 (from baseline of 12.2 ± 6.7), in swollen joint count were −4.2 ± 5.7 (from baseline of 9.8 ± 5.8), and in investigator’s global assessment of RA disease activity were-20.2± 25.1 (from baseline of 51.6± 17.1). Treatment-related adverse events caused 15.9% of patients to discontinue the study prematurely. Serious adverse events possibly related to therapy were reported in 2.4% of patients.

Conclusions: This 6-month study carried out under daily routine practice conditions in a typical sample of RA patients showed a favourable efficacy and safety profile for leflunomide 20mg daily. The study confirms the findings of the earlier phase II and III study programme in more selected patient samples.

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Acknowledgements

We would like to acknowledge the cooperation and commitment of all the local general physicians and their staff without whom the present study would not have been possible. Aventis Pharma, Paris, France, funded the study. The authors have provided no information on conflicts of interest directly relevant to the content of this study.

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Authors and Affiliations

  1. René Descartes University, Institute of Rheumatology, Cochin Hospital, Paris, France

    Minh Nguyen & Philippe Ravaud

  2. Department of Biostatistics, Aventis Laboratories, Paris, France

    Marmar Kabir

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  1. Minh Nguyen
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  2. Marmar Kabir
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Correspondence to Minh Nguyen.

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Nguyen, M., Kabir, M. & Ravaud, P. Short-Term Efficacy and Safety of Leflunomide in the Treatment of Active Rheumatoid Arthritis in Everyday Clinical Use. Clin. Drug Investig. 24, 103–112 (2004). https://doi.org/10.2165/00044011-200424020-00005

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