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Arthritis Care Res (Hoboken). 2019 May 31. doi: 10.1002/acr.23999. [Epub ahead of print]

Low Dose Methotrexate and Mucocutaneous Adverse Events: Results of a Systematic Literature Review and Meta-Analysis of Randomized Controlled Trials.

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Division of Rheumatology.
FAU Charles E. Schmidt College of Medicine.
Department of Orthopedics, General Hospital of Chinese PLA, Beijing, China.
Division of Pharmacoepidemiology, Brigham and Women's Hospital.



Methotrexate (MTX) increases the risk of alopecia and stomatitis, but the prevalence of these adverse events among rheumatic patients taking MTX is poorly defined. We conducted a systematic literature review and meta-analysis to estimate the prevalence of alopecia and stomatitis with MTX in rheumatic diseases.


We searched PubMed, Cochrane Library and CINAHL databases for double blind randomized controlled trials (RCTs) with a MTX monotherapy arm. Alopecia, stomatitis, and oral/mouth ulcers data were extracted. The quality of trials was assessed by two authors. We included trials since 1990 that used at least 10 mg of MTX weekly co-administered with folic or folinic acid. We estimated the prevalence using random effects models as heterogeneity was anticipated. Two estimates of prevalence were included: The lower bound estimate included all trials (assuming no alopecia and stomatitis if not mentioned) and the upper bound estimate only those that specifically described prevalence estimates of alopecia or stomatitis.


Of 3954 studies identified, 20 RCTs were included with a total of 24 MTX monotherapy arms, of which 10 reported the prevalence of alopecia (N = 1,113) and 21 reported stomatitis or mouth/oral ulcers (N = 2,056). The prevalence of alopecia was between 1.0% and 4.9%. The prevalence of stomatitis was between 5.7% and 8.0%.


This meta-analysis gives more precise estimates of mucocutaneous adverse effects that occur in rheumatic disease patients using MTX. These estimates will help inform patient decision making regarding MTX. This article is protected by copyright. All rights reserved.

[Available on 2020-11-30]

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