Effects of Combination Therapy of Methotrexate with Leflunomide & Hydroxychloroquine: Comparative Clinical Trial
Qurrat-ul-Ain Bukhari *
Sir Syed College of Medical Sciences for Girls, Rojhan Street, Block 5, Clifton, Karachi, Pakistan.
Kauser Ismail
Ziauddin Medical University, ST-4-B, Block-6, Clifton, Karachi, Pakistan.
Muzna Hameed Dar
Indus Medical College, Tundo Muhammad Khan, Sindh, Pakistan.
Afshan Abbas
Sir Syed College of Medical Sciences for Girls, Rojhan Street, Block 5, Clifton, Karachi, Pakistan.
Madiha Ata
Indus Medical College, Tundo Muhammad Khan, Sindh, Pakistan.
*Author to whom correspondence should be addressed.
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.
Keywords: Rheumatoid arthritis, methotrexate, leflunomide, Hydroxychloroquine, disease modifying anti-rheumatic drugs.