Efficacy and safety of leflunomide alone and in combination with methotrexate in the treatment of refractory rheumatoid arthritis

Abstract

BACKGROUND: Rheumatoid arthritis patients who develop refractoriness are left with no alternatives other than leflunomide and costly biological response modifiers. Leflunomide, though effective, was associated with adverse events and has not been extensively studied in the Indian population. AIMS: Determination of safety and efficacy of leflunomide alone and if not useful, in combination with methotrexate in patients refractory to conventional disease-modifying agents. SETTING AND DESIGN: Open labeled clinical trial with leflunomide [100 mg, OD x 3 days followed by 20 mg, OD x 6 months], if no improvement at three months, combined with methotrexate [5-7.5 mg, OD x 3 months] at a tertiary care hospital. MATERIALS AND METHODS: The primary endpoint in the improvement in EULAR criteria and secondary endpoints were patient and physician global evaluation, incidence of remission and biochemical and clinical adverse events. STATISTICAL ANALYSIS: Chi square test or Fisher 's exact test and parametric and non-parametric repeat measure ANOVA were used for analysis. RESULTS: Among 84 patients who were included in the study, leflunomide showed improvement and remission in 52 [62%] and 6 [7%] in six months, by intention to treat analysis. Adverse events were observed in 15, discontinuation in 5 and 24 dropped out. With combination in 11 patients, there was improvement and remission in nine [91%] and one [9%] after three months. Adverse events were observed in six and one discontinued. CONCLUSIONS: If regular monitoring of hepatic function and hematological parameters are performed, leflunomide is an effective and safe drug in the Indian population in resistant rheumatoid arthritis patients, especially if used alone.

Chinese Herbal Formula Huayu-Qiangshen-Tongbi Decoction Compared With Leflunomide in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis: An Open-Label, Randomized, Controlled, Pilot Study

“…Reported AEs suggested that the most significant safety issue of MTX + LEF combination was potential liver toxicity, which was undoubtedly consistent with the real situation of LEF usage in RA treatment (48). In our study, liver abnormalities occurred in 8.9% of the MTX + LEF, which was lower than those reported in several other RCTs in RA (28,29). The result of the previous study found that the incidence of alanine aminotransferase/aspartate aminotransferase elevations increased ∼ 2-5 folds in the combination of MTX and LEF, which depended on the dosages of MTX (48).…”

“…During the 24-week trial, the treatment with MTX + HQT resulted in significant improvement in clinical signs and symptoms of RA, including joint pain, joint swelling, morning stiffness duration, and measures of quality-of-life outcome, as well as in many inflammatory indicators, such as CRP, ESR, and the autoantibody RF. Comparing with MTX + LEF (a recommended therapy for refractory RA) (28)(29)(30), MTX + HQT led to a similar improvement in terms of patients achieving ACR20, ACR50, ACR70, cDAI, LDA, and remission responses and to moderate or good improvement in DAS28-CRP. In this pilot study, the combinational therapy of HQT with MTX effectively and safely alleviated symptoms and signs of patients with active RA.…”