{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:02:12Z","timestamp":1789704132497,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Methotrexate, a folic acid analog, is the conventional systemic anti\u2010psoriatic agent most commonly chosen for combination with biologics in the treatment of psoriasis. Real\u2010world long\u2010term safety data of this combination versus biologic treatment alone in dermatological practice are sparse. Here, we present results of a comparative retrospective study of laboratory dynamics and adverse events in psoriatic patients receiving a tumor necrosis factor (TNF)\u2010\u03b1 antagonist (adalimumab or etanercept) with and without concomitant methotrexate (176 treatment courses, mean duration of 629\u00a0days). Co\u2010treatment with methotrexate significantly (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) correlated with a decrease of leukocyte, neutrophil and erythrocyte counts and an increase of glutamate pyruvate transaminase (GPT) (Pearson correlation, n\u00a0&gt;\u00a0148). The relative risk for a Common Terminology Criteria for Adverse Events (CTCAE) grade 1\u20132 laboratory adverse event was significantly elevated to 1.11 for anemia and 1.16 for a GPT increase if the patients received concomitant methotrexate at the time the laboratory test was performed. Combination treatment was given for equal or more than 30% of the time (MTX<jats:sub>\u226530%<\/jats:sub>) during 12% of the treatment courses. During these treatment courses, dynamics of leukocyte (\u22128.1%), neutrophil (\u22128.1%), erythrocyte (\u22123.2%) counts and GPT (+16.9%) from baseline to average under treatment were significantly more pronounced. CTCAE grade 3\u20134 laboratory adverse events occurred in 9.5% and 5.2% of treatment courses with and without MTX<jats:sub>\u226530%<\/jats:sub>, respectively (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.70), and affected transaminases in 90% of the cases. Methotrexate was discontinued due to CTCAE grade 3\u20134 laboratory adverse events in 4.25% of the treatment courses with MTX of 30% or more. Elevated baseline \u03b3\u2010glutamyl transferase levels significantly predicted the occurrence of CTCAE grade 3\u20134 laboratory adverse events and should trigger investigations for pre\u2010existing liver disease or alcohol abuse. In conclusion, our comparative data supplement previous short\u2010term studies and support a tolerable long\u2010term safety profile of the combination treatment. However, given the additional toxicities and low evidence for benefits, alternative options such as biologic monotherapy or switching to a different biologic should be considered in a dermatological setting.<\/jats:p>","DOI":"10.1111\/1346-8138.15754","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T13:20:52Z","timestamp":1611148852000},"page":"835-843","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Long\u2010term safety of combination treatment with methotrexate and tumor necrosis factor (TNF)\u2010\u03b1 antagonists versus TNF\u2010\u03b1 antagonists alone in psoriatic patients"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1579-626X","authenticated-orcid":false,"given":"Jochen H. O.","family":"Hoffmann","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Knoop","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunt","family":"Sch\u00e4kel","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander H.","family":"Enk","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva N.","family":"Hadaschik","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"Schubert I: Barmer Arzneimittel Report 2019","author":"Grandt D","year":"2019"},{"key":"e_1_2_6_3_1","first-page":"1","article-title":"Treatment adherence and persistence of five commonly prescribed medications for moderate to severe psoriasis in a U.S. commercially insured population","author":"Wu B","year":"2020","journal-title":"J Dermatolog 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