{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T03:44:54Z","timestamp":1775619894337,"version":"3.50.1"},"reference-count":21,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:00:00Z","timestamp":1692921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The constant use of disease modifying anti rheumatic drugs affects the functioning of multiple organs inside the body. Some drugs are more toxic than others. The present case control investigation was designed to evaluate the comparative toxicity of methotrexate and leflunomide on multiple organs in rheumatoid arthritis patients. For this purpose, 100 subjects with confirmed rheumatoid arthritis condition were recruited form tertiary care center. Whereas 50 age matched controls were recruited from the local healthy population. Participants of the study were categorized into three groups with equal numbers of subjects in each group (n = 50). Group 1 comprised rheumatoid arthritis patients on methotrexate treatment, group 2 included rheumatoid arthritis patients on leflunomide treatment and group 3 were healthy subjects. Cardiac and respiratory response was evaluated by monitoring blood pressure, pulse and breathing rate and spot oxygen saturation. Stress on liver was estimated by measuring change in liver enzymes (alanine transaminase, aspartate aminotransferase, and alkaline phosphatase) and total bilirubin. While, degree of renal impairment was assessed by calculating glomerular filtration rate, serum creatinine, urinary urea and uric acid. For statistical interpretation, data was subjected to independent student \u201ct\u201d test and analysis of variance (one way ANOVA) for mean variations. Both methotrexate and leflunomide elevated the systolic and diastolic blood pressure and pulse rate. Leflunomide maintained the oxygen saturation at 96.7%, whereas methotrexate exerted serious effect on spot oxygen saturation by reducing it significantly to 93.25% than healthy subjects. Hepatotoxicity manifested by sustained use of leflunomide was perceptible in this study group. Whereas, both methotrexate and leflunomide influenced renal function as indicated by marked increase in blood urea nitrogen (P = 0.001), serum creatinine (P = 0.007) and reduced glomerular filtration rate (P&lt;0.0001). However, use of methotrexate demonstrated significant (P&lt;0.0001) reduction in serum uric acid and urinary urea levels. Methotrexate is more injurious to heart, blood vessels and kidneys than leflunomide but it is less noxious to hepatic parenchyma. Contrarily, leflunomide usage is comparatively better option for respiratory, cardiovascular, and renal health but dangerous to liver. Thus, a single drug can\u2019t be prescribed for the treatment of rheumatoid arthritis for longer management of arthritis patients.<\/jats:p>","DOI":"10.1371\/journal.pone.0290668","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T17:34:50Z","timestamp":1692984890000},"page":"e0290668","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Comparative analysis of multiorgan toxicity induced by long term use of disease modifying anti-rheumatic drugs"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2717-2024","authenticated-orcid":true,"given":"Tamseela","family":"Mumtaz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayesha","family":"Tahir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maham Almas","family":"Tariq","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Amir","family":"Iqbal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,8,25]]},"reference":[{"issue":"7","key":"pone.0290668.ref001","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1002\/art.42089","article-title":"Prevalence trends of site-specific osteoarthritis from 1990 to 2019: Findings from the global burden of disease study 2019","volume":"74","author":"H Long","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"pone.0290668.ref002","unstructured":"GBD 2019: Global burden of 369 diseases and injuries in 204 countries and territories, 1990\u20132019: a systematic analysis for the Global Burden of Disease Study 2019. https:\/\/vizhub.healthdata.org\/gbd-results\/."},{"issue":"2","key":"pone.0290668.ref003","first-page":"393","article-title":"Depression in rheumatoid arthritis and its relation to disease activity","volume":"31","author":"MY Imran","year":"2015","journal-title":"PaK J Med Sci"},{"issue":"4","key":"pone.0290668.ref004","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/S0889-857X(05)70170-8","article-title":"Hormonal alterations in rheumatoid arthritis, including the effects of pregnancy","volume":"26","author":"KS Kanik","year":"2000","journal-title":"Rheum Dis Clin North Am"},{"issue":"7","key":"pone.0290668.ref005","doi-asserted-by":"crossref","first-page":"10018","DOI":"10.1002\/jcp.27860","article-title":"Strategies toward rheumatoid arthritis therapy; the old and the new","volume":"234","author":"M Abbasi","year":"2019","journal-title":"J. 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