Effects of Combination Therapy of Methotrexate with Leflunomide & Hydroxychloroquine: Comparative Clinical Trial

Abstract

Aims: To study the role of combination therapies in the treatment of rheumatoid arthritis. Study Design:  This an open-label, randomized 180-days clinical trial. Place and Duration of Study: This study was conducted in the Department of Pharmacology and Therapeutics, BMSI and Medical unit ward 6, after approval of JPMC ethical committee, between March 2013 and May 2014. Methodology: We included 90 patients (69 women, 21 men; age range 28-62 years) which were divided into two groups, A and B. 44 patients of group A received methotrexate (MTX) 7.5-20 mg/ week orally and Leflunomide (LEF) 10-20 mg/ day QD orally as maximally tolerated. 46 patients of group B were given MTX 7.5-20 mg/ week orally and Hydroxychloroquine (HCQ) 200 mg twice daily orally as maximally tolerated. Results: Comparing the combination of group A with group B, group A showed highly significant improvement in mean patient’s global assessment (1.4 ± 0.66) and mean pain (1.3 ± 1.11) as compared to group B (2.4 ± 1.14, 2.2 ± 1.49). The drugs of group B showed significant improvement in mean physician’s global assessment (1.7 ± 0.92) and mean morning stiffness (49.2 ± 10.59) as compared to group A (2.8 ± 0.97, 54.4 ± 10.14). Combination treatment of group B showed significantly lower adverse effects (4.3%) as compared to group A (11.4%). Statistical analysis revealed that patients receiving both the combinations responded equally in terms of effects but group B showed significantly better in terms of adverse effects. Conclusion: Both combinations of MTX & LEF and MTX & HCQ were well tolerated but the efficacy of MTX and HCQ was significantly superior in terms of adverse effects to the combination of MTX and LEF.