The side-effects and efficacy of leflunomide in Japanese patients with rheumatoid arthritis

Aims:  To investigate the efficacy and safety of leflunomide, including the side-effects, we assessed 84 rheumatoid arthritis (RA) patients who received leflunomide treatment. Methods:  We analyzed the C-reactive protein (CRP), white blood cell count (WBC), KL-6, and visual analogue scale (VAS) scores, modified Stanford Health Assessment Questionnaire (MHAQ) score, American Rheumatism Association score (ACR20 and ACR50) within a time course after treatment with leflunomide. We treated 84 RA patients, 12 male and 72 female from 28 to 81-years-old, with an average age of 63.5 years. The patients were divided into three groups: a group consisting of 38 patients who received 100 mg/day of leflunomide for 3 days followed by 20 mg/day thereafter; a second group of 11 patients who received a no-loading dose of 10 mg/day; and a third group of 35 patients who received a no loading dose of 20 mg/day. Results:  The 50% decrease of CRP seen in 2 weeks was 52% of the total of 84 patients. The WBC score did not change significantly after the medication was given. The KL-6 score did not change significantly, either. The VAS pain score improved 4 weeks later, and then further improved 8 weeks later. Therefore, RA patients using leflunomide obtained pain relief 4 weeks after commencing medication. The MHAQ score did not change significantly until 8 weeks after the patients started the medication. ACR20 was 62% and ACR50 was 38% at 8 weeks after treatment. The side-effects of leflunomide observed in our patients were rash, respiratory infection, diarrhea, nausea, alopecia, muscle pain, headache, dizziness and general fatigue. Twenty-three out of 84 patients experienced side-effects (27%), and 48/84 (57%) experienced withdrawal. In our hospital, there were no patients who developed severe interstitial pneumonia (IP) or who died after taking leflunomide; however, the incidence of side-effects of the 100 mg/day loading dose (42.1%) was 2.5 times higher than in the patients who received 20 mg/day (17.1%) of a no-loading dose. Conclusion:  Because of this, it is possible that a 100 mg/day loading dose is a relatively high risk dose in terms of causing side-effects, especially for severely ill RA patients with a high CRP level.