Leflunomide and rheumatoid arthritis: a systematic review of effectiveness, safety and cost implications.

OBJECTIVE: To assess the effectiveness, safety and cost implications of leflunomide treatment for rheumatoid arthritis. DESIGN: Systematic review. SETTING: Four trials retrieved from Medline, Embase, the Cochrane Library, Econlit, HMIC (Dhdata), HMIC (Helmis), HMIC (King's Fund Database) and Best Evidence3. MAIN OUTCOME MEASURES: Efficacy measures (including tender joint counts, swollen joint counts, assessment of functioning, Health Assessment Questionnaire, Modified Health Assessment Questionnaire, pain (visual analogue scale), Erythrocyte Sedimentation Rate, C-reactive Protein), radiological progression and treatment adverse events. RESULTS: Leflunomide therapy was demonstrated to be significantly superior to placebo in relation to the efficacy outcome measures and it slowed the radiological progression of patients' disease in three studies. Treatment success and duration of sustained response were also significantly superior than on placebo, as were quality of life measures. Leflunomide treatment was comparable to sulphasalazine and methotrexate with respect to efficacy, radiological progression and quality of life measures. The most common adverse effects leading to withdrawal from leflunomide treatment were gastrointestinal symptoms (diarrhoea and nausea), allergic reactions (rash and pruritus), alopecia, dyspepsia, hypertension and elevated transaminase levels. Weight loss and dizziness have also been reported for leflunomide therapy. Leflunomide is more expensive than most DMARDs, costing about pound400 a year more than sulphasalazine. CONCLUSION: Despite the small number of published articles relating to leflunomide treatment, the evidence suggests that leflunomide is similar in efficacy to both sulphasalazine and methotrexate, although with a differential pattern of side-effects. There is a need for further research to assess the long-term outcomes of leflunomide treatment.