Effects of Combination Therapy of Methotrexate with Leflunomide & Hydroxychloroquine: Comparative Clinical Trial
Journal of Pharmaceutical Research International,
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.
- Rheumatoid arthritis
- disease modifying anti-rheumatic drugs.
How to Cite
Howard R Smith, MD; Chief Editor: Herbert S Diamond, MD. What is the global prevalence of rheumatoid arthritis (RA) among different age groups and ethnicities? Medscape. Updated; Feb 07, 2020.
Ehtisham A, Saira B, Adnan K, Uzma H. Prevalence of arthritis in India and Pakistan: A review. Rheumatology International. 2011;31(7):849-55.
Singh JA, Saag KG, et al. American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care and Research. 2015.
Kelly JC. Rheumatoid arthritis: Updated recommendations released. Medscape Medical News; May 28, 2015; Accessed: June 30, 2015.
Smolen JS, Breedveld FC, Burmester GR, Bykerk V, Dougados M, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis; 2015.
Hazlewood GS, Barnabe C, Tomlinson G et al. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis: A network meta-analysis. Cochrane Database Syst Rev 2016;(8): 139-42.
WHO Model List of Essential Medicines.World Health Organization, 2013. Retrieved 2014.
Goldminz, AM, et al. CCL20 and IL22 Messenger RNA Expression After adalimumab vs Methotrexate Treatment of Psoriasis: A Randomized Clinical Trial. JAMA dermatology. 2015;151:837–46.
Pinto P, Dougados M. Leflunomide in clinical practice. Acta Reumatológica Portuguesa. 2006;31:215–24.
Smolen JS. et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological diseasemodifying antirheumatic drugs. Ann. Rheum. Dis. 2019;79:685–99.
Elshaer RE. et al. Leflunomide-induced liver injury in mice: Involvement of TLR4 mediated activation of PI3K/mTOR/ NFkappaB pathway. Life Sci., 2019;235-40.
James RO, Leff R, Paulsen G, Haire C, Mallek J, Eckhoff PJ, et al. Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: Results of a two-year, randomized, double-blind, placebo-controlled trial. Arthrits and Rheum. 2002; 46:1164-70.
Reips U, Funke F. Interval-level measurement with visual analogue scales in Internet-based research: VAS Generator by University of Zürich, Zürich, Switzerland and University of Tübingen, Tübingen, Germany. Behavior Res Methods. 2008; 40:699-04.
Adopted from National Institutes of Health Warren Grant Magnuson Clinical Center Pain Intensity Instruments; 2003.
McInnes IB, Thompson L, Giles JT, Bathon JM, Salmon JE, Beaulieu AD et al. EKect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo controlled study. Ann Rheum Dis 2015;74(4):694-02.
Lisa Schapink, Cornelia HM, van den Ende, Laura AHA, Gevers Annelies E. van Ede, Alfons A. den Broeder. The effects of methotrexate and hydroxychloroquine combination therapy vs methotrexate monotherapy in early rheumatoid arthritis patients Rheumatology. 2019;58: 131-34.
Buckley F, Finckh A, Huizinga TW, et al. Comparative efficacy of novel DMARDs as monotherapy and in combination with methotrexate in rheumatoid arthritis patients with inadequate response to conventional DMARDs: a network meta-analysis. J Manag Care Spec Pharm. 2015;21:409–23.
Fleischmann R, Wollenhaupt J, Takiya L, et al. Safety and maintenance of response for tofacitinib monotherapy and combination therapy in rheumatoid arthritis: an analysis of pooled data from open-label long-term extension studies. RMD Open. 2017;3.
Jobanputra W, Douglas K, Burls A. A survey of British rheumatologists' DMARD preferences for rheumatoid arthritis. Rheum. 2004;43:206-10.
Shashikumar NS, Shivamurthy MC, Chandrashekara S. Evaluation of efficacy of combination of methotrexate and hydroxychloroquine with leflunomide in active rheumatoid arthritis. Indian J Pharmacol. 2010;42:358–61.
Mikuls TR, O’Dell J. The changing face of rheumatoid arthritis therapy: results of serial surveys. Arthritis Rheum. 2000;43: 64-75.
Combe B., Scott DL, Wolfe F, Huizinga TW. Leflunomide combined with conventional disease-modifying antirheumatic drugs or biologics in patients with rheumatoid arthritis. Joint Bone Spine. 2006;73(6):587-90.
Scott DL, Ma MH, Kingsley GH. Comparison of combination therapies in the treatment of rheumatoid arthritis: leflunomide-anti-TNF-alpha versus methotrexate-anti-TNF-alpha. Clin Rheumatol. 2010; 29(5):517-24.
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