Comparison of Liver Injury in Patients Taking Methotrexate and Leflunamide in Rheumatoid Arthritis
DOI:
https://doi.org/10.61919/jhrr.v4i2.570Keywords:
Rheumatoid arthritis, Methotrexate, Leflunomide, DMARDs, hepatotoxicity, liver injury, ALT, AST, autoimmune disease, liver function monitoringAbstract
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints, leading to inflammation and potential joint damage. Methotrexate (MTX) and Leflunomide (LEF) are commonly used disease-modifying antirheumatic drugs (DMARDs) for RA, but their hepatotoxic effects require careful monitoring.
Objective: This study aimed to compare the incidence of liver injury in RA patients treated with Methotrexate versus Leflunomide.
Methods: This prospective study was conducted from January 2023 to June 2023 and included 80 RA patients aged 20 years or older, who reported to the Medicine Department at Combined Military Hospital (CMH) Lahore. Patients were divided into two groups: Group A received 20 mg/day Methotrexate (n=40), and Group B received 20 mg/day Leflunomide (n=40). Exclusion criteria included pregnant females, patients with hepatitis B or C, those with known allergies to Methotrexate or Leflunomide, and alcoholics. Baseline investigations, including liver enzyme levels (ALT/AST), were performed, and patients were monitored every three months. Hepatotoxicity was defined as an increase in ALT/AST levels to at least twice the upper limit of normal (ULN). Data were analyzed using SPSS version 25.0, with mean and standard deviation for quantitative data and frequency and percentage for qualitative data. The Chi-square test was used to compare variables, with p<0.05 considered statistically significant.
Results: Out of 80 patients, 43 (53.75%) were female, and 37 (46.25%) were male. In Group A, 7 patients (17.5%) had elevated ALT/AST levels, while 6 patients (15%) in Group B exhibited elevated liver enzymes. The mean age was 52.4 ± 8.3 years in Group A and 50.6 ± 9.1 years in Group B. The mean BMI was 26.7 ± 3.5 kg/m² in Group A and 27.1 ± 3.8 kg/m² in Group B. No statistically significant difference in hepatotoxicity was observed between the two groups (p>0.05).
Conclusion: Methotrexate and Leflunomide were equally effective in treating RA, with no significant difference in liver toxicity observed between the two groups. Both medications have comparable risks for hepatotoxicity, necessitating regular liver function monitoring during treatment.
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References
Lee JE, Kim IJ, Cho MS, Lee J. A Case of Rheumatoid Vasculitis Involving Hepatic Artery in Early Rheumatoid Arthritis. J Korean Med Sci. 2017 Jul 1;32(7):1207-10.
van der Woude D, van der Helm-van AH. Update on the Epidemiology, Risk Factors, and Disease Outcomes of Rheumatoid Arthritis. Best Pract Res Clin Rheumatol. 2018 Apr 1;32(2):174-87.
Fraenkel L, Bathon JM, England BR, St. Clair EW, Arayssi T, Carandang K, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2021 Jul;73(7):1108-23.
Sfikakis PP. The First Decade of Biologic TNF Antagonists in Clinical Practice: Lessons Learned, Unresolved Issues and Future Directions. TNF Pathophysiology. 2010;11:180-210.
Ishaq M, Muhammad JS, Hameed K, Mirza AI. Leflunomide or Methotrexate? Comparison of Clinical Efficacy and Safety in Low Socio-Economic Rheumatoid Arthritis Patients. Mod Rheumatol. 2011 Aug 1;21(4):375-80.
Paulus HE. The Use of Combinations of Disease‐Modifying Antirheumatic Agents in Rheumatoid Arthritis. Arthritis Rheum. 1990 Jan;33(1):113-20.
Weinblatt ME, Kaplan H, Germain BF, Block S, Solomon SD, Merriman RC, et al. Methotrexate in Rheumatoid Arthritis. A Five‐Year Prospective Multicenter Study. Arthritis Rheum. 1994 Oct;37(10):1492-8.
Schnabel A, Gross WL. Low-Dose Methotrexate in Rheumatic Diseases-Efficacy, Side Effects, and Risk Factors for Side Effects. Semin Arthritis Rheum. 1994;23:310-27.
Katchamart W, Trudeau J, Phumethum V, Bombardier C. The Efficacy and Toxicity of Methotrexate (MTX) Monotherapy vs. MTX Combination Therapy with Non-Biologic Disease-Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. Ann Rheum Dis. 2008 Dec 3.
Wang L, Ma L, Lin Y, Liu X, Xiao L, Zhang Y, et al. Leflunomide Increases Hepatic Exposure to Methotrexate and Its Metabolite by Differentially Regulating Multidrug Resistance–Associated Protein Mrp2/3/4 Transporters via Peroxisome Proliferator–Activated Receptor α Activation. Mol Pharmacol. 2018 Jun 1;93(6):563-74.
Bird P, Griffiths H, Tymms K, Nicholls D, Roberts L, Arnold M, et al. The SMILE Study—Safety of Methotrexate in Combination with Leflunomide in Rheumatoid Arthritis. J Rheumatol. 2013 Mar 1;40(3):228-35.
Nisar A, Farooqi AZ, Aziz W, Rasheed U. Efficacy of Methotrexate Versus Leflunomide Versus Combination of Both in Active Rheumatoid Arthritis. Ann PIMS ISSN. 2016;1815:2287.
Riaz S, Mahmud TE, Rasheed A, Akhtar AW, Javed A, Javaid U. Risk of Hepatotoxicity in Leflunomide Vs Methotrexate in Treatment of Rheumatoid Arthritis. Pak J Med Health Sci. 2022 Jun 18;16(05):715.
Alfaro-Lara R, Espinosa-Ortega HF, Arce-Salinas CA, Precis Study Group. Systematic Review and Meta-Analysis of the Efficacy and Safety of Leflunomide and Methotrexate in the Treatment of Rheumatoid Arthritis. Reumatol Clin. 2019 May 1;15(3):133-9.
Choi SR, Park JW, Lee EB, Park JK. Initial Methotrexate Dosage Is Not Associated with an Increased Risk of Liver Toxicity in Patients with Rheumatoid Arthritis. Clin Rheumatol. 2021 Nov;40(11):4493-500.
Alves JA, Fialho SC, Morato EF, Castro GR, Zimmermann AF, Ribeiro GG, et al. Liver Toxicity Is Rare in Rheumatoid Arthritis Patients Using Combination Therapy with Leflunomide and Methotrexate. Rev Bras Reumatol. 2011;51:141-4.
Mumtaz T, Tahir A, Tariq MA, Iqbal MA. Comparative Analysis of Multiorgan Toxicity Induced by Long Term Use of Disease Modifying Anti-Rheumatic Drugs. PLoS One. 2023 Aug 25;18(8):e0290668.
Avouac J, Degrave R, Vergneault H, Combier A, Wanono S, Boisson M, et al. Risk of Liver Fibrosis Induced by Methotrexate and Other Rheumatoid Arthritis Medications According to the Fibrosis-4 Index. Clin Exp Rheumatol. 2022 Jan 1;40(1):150-7.
González-Gay MA, Heras-Recuero E, Blázquez-Sánchez T, Castañeda S, Largo R. Leflunomide as a therapeutic alternative to methotrexate as a glucocorticoid-sparing agent in polymyalgia rheumatica. Rheumatology Advances in Practice. 2024 Jan 1;8(2):rkae047.
Niyasom C, Soponkanaporn S, Vilaiyuk S, Lertudomphonwanit C, Getsuwan S, Tanpawpong P, Kaewduang P, Sobhonslidsuk A. Use of transient elastography to assess hepatic steatosis and fibrosis in patients with juvenile idiopathic arthritis during methotrexate treatment. Clinical Rheumatology. 2024 Jan;43(1):423-33.
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Copyright (c) 2024 Maheen Zahid, Adnan Manzar, Waqas Qureshi, Javed Iqbal, Fizza Khursheed, Asma Saeed, Sahar Abdul Rauf, Ishfaq Ahmed``, Muhammad Farrukh Habib
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