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Long‐term safety of combination treatment with methotrexate and tumor necrosis factor (TNF)‐α antagonists versus TNF‐α antagonists alone in psoriatic patients
Author(s) -
Hoffmann Jochen H. O.,
Knoop Christian,
Schäkel Kunt,
Enk Alexander H.,
Hadaschik Eva N.
Publication year - 2021
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/1346-8138.15754
Subject(s) - medicine , adalimumab , adverse effect , methotrexate , psoriasis , elevated transaminases , concomitant , etanercept , gastroenterology , common terminology criteria for adverse events , tumor necrosis factor alpha , pharmacology , dermatology
Methotrexate, a folic acid analog, is the conventional systemic anti‐psoriatic agent most commonly chosen for combination with biologics in the treatment of psoriasis. Real‐world long‐term 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)‐α antagonist (adalimumab or etanercept) with and without concomitant methotrexate (176 treatment courses, mean duration of 629 days). Co‐treatment with methotrexate significantly ( P < 0.05) correlated with a decrease of leukocyte, neutrophil and erythrocyte counts and an increase of glutamate pyruvate transaminase (GPT) (Pearson correlation, n > 148). The relative risk for a Common Terminology Criteria for Adverse Events (CTCAE) grade 1–2 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 ≥30% ) during 12% of the treatment courses. During these treatment courses, dynamics of leukocyte (−8.1%), neutrophil (−8.1%), erythrocyte (−3.2%) counts and GPT (+16.9%) from baseline to average under treatment were significantly more pronounced. CTCAE grade 3–4 laboratory adverse events occurred in 9.5% and 5.2% of treatment courses with and without MTX ≥30% , respectively ( p = 0.70), and affected transaminases in 90% of the cases. Methotrexate was discontinued due to CTCAE grade 3–4 laboratory adverse events in 4.25% of the treatment courses with MTX of 30% or more. Elevated baseline γ‐glutamyl transferase levels significantly predicted the occurrence of CTCAE grade 3–4 laboratory adverse events and should trigger investigations for pre‐existing liver disease or alcohol abuse. In conclusion, our comparative data supplement previous short‐term studies and support a tolerable long‐term 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.