FREQUENCY OF METHOTREXATE INDUCED HEPATOTOXICITY IN PATIENTS WITH RHEUMATOID ARTHRITIS
DOI:
https://doi.org/10.54112/pjicm.v5i01.61Keywords:
Methotrexate Hepatotoxicity Rheumatoid Arthritis Dose-Dependent Liver EnzymesAbstract
Background: Methotrexate (MTX) is a cornerstone drug in the management of rheumatoid arthritis (RA), but its use is associated with potential adverse effects, notably hepatotoxicity. Identifying the frequency and contributing factors to MTX-induced liver toxicity is essential for optimizing therapeutic safety in RA patients. Objective: To evaluate the frequency and associated risk factors of methotrexate-induced hepatotoxicity among patients with rheumatoid arthritis. Study Design: Descriptive cross-sectional study. Setting: This study was conducted at the Department of Medicine at Lady Reading Hospital, Peshawar. Duration of Study: The study was conducted over six months [11-September-2024 to 11-March-2025]. Methods: A total of 78 patients diagnosed with RA and undergoing MTX therapy, irrespective of age and gender, were enrolled. Hepatotoxicity was defined as serum alanine aminotransferase (ALT) levels exceeding twice the standard upper limit. Data regarding age, gender, MTX dosage, and liver function tests were recorded. Statistical analysis was performed using SPSS version 24. Chi-square and t-tests were used to assess associations, with a p-value ≤ 0.05 considered statistically significant. Results: The mean age of participants was 45.29 ± 12.38 years. Most were female (56.4%), while males accounted for 43.6%. Hepatotoxicity was observed in 19.2% of patients. A significant association was found between hepatotoxicity and higher MTX dosage (25 mg/week) (p = 0.01). No significant correlations were identified with age (p = 0.39) or gender (p = 0.39). Conclusion: Methotrexate-induced hepatotoxicity was found in nearly one-fifth of RA patients, with higher MTX doses significantly associated with liver enzyme elevation. These findings highlight the importance of regular liver function monitoring, particularly in patients receiving higher MTX dosages.
References
Klareskog L, Rönnelid J, Saevarsdottir S, Padyukov L, Alfredsson L. The importance of differences; On environment and its interactions with genes and immunity in the causation of rheumatoid arthritis. J Intern Med. 2020;287(5):514-533.
Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388(10055):2023-2038.
Sparks JA. Rheumatoid Arthritis. Ann Intern Med. 2019;170(1):1-16.
Bullock J, Rizvi SAA, Saleh AM, Ahmed SS, Do DP, Ansari RA, Ahmed J. Rheumatoid Arthritis: A Brief Overview of the Treatment. Med Princ Pract. 2018;27(6):501-07.
Cross M, Smith E, Hoy D, Carmona L, Wolfe F, Vos T, Williams B, Gabriel S, Lassere M, Johns N, Buchbinder R, Woolf A, March L. The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(7):1316-22.
Smolen JS, Landewé R, Breedveld FC, Buch M, Burmester G, Dougados M, Emery P, Gaujoux-Viala C, Gossec L, Nam J, Ramiro S. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492-509.
Salliot C, van der Heijde D. Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis. 2009;68(7):1100-4.
Patel D, Shelbaya A, Cheung R, Aggarwal J, Park SH, Coindreau J. Cost-effectiveness of early treatment with originator biologics or their biosimilars after methotrexate failure in patients with established rheumatoid arthritis. Adv Ther. 2019;36:2086-95.
Li S, Li J, Peng L, Li Y, Wan X. Cost-effectiveness of triple therapy vs. Biologic treatment sequence as first-line therapy for rheumatoid arthritis patients after methotrexate failure. Rheumatol Ther. 2021;8:775-91.
Van Ede AE, Laan RF, Rood MJ, Huizinga TW, Van De Laar MA, Denderen CJ, Westgeest TA, Romme TC, De Rooij DJ, Jacobs MJ, De Boo TM. Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty‐eight–week, multicenter, randomized, double‐blind, placebo‐controlled study. Arthritis & Rheumatism. J Am Coll Rheumatol. 2001;44(7):1515-24.
Laharie D, Terrebonne E, Vergniol J, Chanteloup E, Chabrun E, Couzigou P, De Ledinghen V. Foie et méthotrexate. Gastroentéro Clin Biol. 2008;32(2):134-42.
Erickson AR, Reddy V, Vogelgesang SA, West SG. Usefulness of the American College of Rheumatology recommendations for liver biopsy in methotrexate‐treated rheumatoid arthritis patients. Arthritis & Rheumatism. J Am Coll Rheumatol. 1995;38(8):1115-9.
Willkens RF, Leonard PA, Clegg DO, Tolman KG, Ward JR, Marks CR, Greene ML, Roth GJ, Jackson CG, Cannon GW. Liver histology in patients receiving low dose pulse methotrexate for the treatment of rheumatoid arthritis. Ann Rheum Dis. 1990;49(8):591-3.
Berkowitz RS, Goldstein DP, Bernstein MR. Ten years' experience with methotrexate and folinic acid as primary therapy for gestational trophoblastic disease. Gynecol Oncology. 1986;23(1):111-8.
Gilani ST, Khan DA, Khan FA, Ahmed M. Adverse effects of low dose methotrexate in rheumatoid arthritis patients. J Coll Physicians Surg Pak. 2012;22(2):101-4.
Sotoudehmanesh R, Anvari B, Akhlaghi M, Shahraeeni S, Kolahdoozan S. Methotrexate hepatotoxicity in patients with rheumatoid arthritis. Middle East J Dig Dis. 2010;2(2):104-9.
Bilal M, Shaheen G, Mustafa SH, Nazir M, Ahmad Z, Khan TM, et al. Hepatic safety of low dose methotrexate therapy in patients with rheumatoid arthritis. Prof Med J. 2022;29(6):791-6.
Babar MA, Ansari IA, Samo JA. Determine the prevalence of methotrexate induced hepatotoxicity in rheumatoid arthritis patients whom treated with low dose methotrexate. Pak J Med Health Sci. 2019;13(3):865-7.
Parvin MS, Rashid MU, Ekram AR, Begum HA. Early hepatotoxicity of methotrexate in rheumatoid arthritis. TAJ. 2008;21(2):147-51.
García DS, Saturnasky EI, Poncino D, et al. Hepatic toxicity by methotrexate with weekly single doses associated with folic acid in rheumatoid and psoriatic arthritis. Ann Hepatol. 2019;18(6):765-769.
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