A Call to Systematically Monitor for Adverse Events in Users of Low-Dose Methotrexate Therapy
Authors: Vivian P. Bykerk
Journal: Annals of Internal Medicine (2020)

Editorials17 March 2020A Call to Systematically Monitor for Adverse Events in Users of Low-Dose Methotrexate TherapyVivian P. Bykerk, MDVivian P. Bykerk, MDHospital for Special Surgery and Weill Cornell Medical College, New York, New York (V.P.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-0435 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Since small randomized trials demonstrated its efficacy in the 1980s, methotrexate (MTX) has become a first-line treatment of rheumatic diseases with inflammatory arthritis (IA), particularly rheumatoid arthritis (RA). However, hepatic and other toxicities were recognized from the outset, both asymptomatic (intermittent elevations in liver enzyme levels) and symptomatic (such as nausea, malaise, diarrhea, and mucosal ulcers), often requiring dose reductions of MTX. Recurrent liver enzyme elevations are associated with cirrhosis in fewer than 2% of long-term users, although liver biopsy should be considered if levels of aspartate aminotransferase are elevated in 5 or more of 9 serial measurements. As advanced ...References1. Vanni KMM, Lyu H, Solomon DH. Cytopenias among patients with rheumatic diseases using methotrexate: a meta-analysis of randomized controlled clinical trials. Rheumatology (Oxford). 2019. [PMID: 31504937] doi:10.1093/rheumatology/kez343 CrossrefMedlineGoogle Scholar2. Lalani R, Lyu H, Vanni K, et al. Low dose methotrexate and mucocutaneous adverse events: results of a systematic literature review and meta-analysis of randomized controlled trials. Arthritis Care Res (Hoboken). 2019. [PMID: 31150157] doi:10.1002/acr.23999 CrossrefMedlineGoogle Scholar3. 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; 68:1100-4. [PMID: 19060002] doi:10.1136/ard.2008.093690 CrossrefMedlineGoogle Scholar4. Roubille C, Haraoui B. Interstitial lung diseases induced or exacerbated by DMARDS and biologic agents in rheumatoid arthritis: a systematic literature review. Semin Arthritis Rheum. 2014;43:613-26. [PMID: 24231065] doi:10.1016/j.semarthrit.2013.09.005 CrossrefMedlineGoogle Scholar5. Andersen KM, Kelly A, Lyddiatt A, et al. Patient perspectives on DMARD safety concerns in rheumatology trials: results from inflammatory arthritis patient focus groups and OMERACT attendees discussion. J Rheumatol. 2019;46:1168-72. [PMID: 30770516] doi:10.3899/jrheum.181185 CrossrefMedlineGoogle Scholar6. Solomon DH, Glynn RJ, Karlson EW, et al. Adverse effects of low-dose methotrexate. A randomized trial. Ann Intern Med. 2020;172:369-80. doi:10.7326/M19-3369 LinkGoogle Scholar7. Ridker PM, Everett BM, Pradhan A, et al; CIRT Investigators. Low-dose methotrexate for the prevention of atherosclerotic events. N Engl J Med. 2019; 380:752-62. [PMID: 30415610] doi:10.1056/NEJMoa1809798 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Hospital for Special Surgery and Weill Cornell Medical College, New York, New York (V.P.B.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-0435.Corresponding Author: Vivian P. Bykerk, MD, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021; e-mail, [email protected]edu.This article was published at Annals.org on 18 February 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAdverse Effects of Low-Dose Methotrexate Daniel H. Solomon , Robert J. Glynn , Elizabeth W. Karlson , Fengxin Lu , Cassandra Corrigan , Josh Colls , Chang Xu , Jean MacFadyen , Medha Barbhaiya , Nancy Berliner , Paul F. Dellaripa , Brendan M. Everett , Aruna D. Pradhan , Sarah P. Hammond , Meredith Murray , Deepak A. Rao , Susan Y. Ritter , Anna Rutherford , Jeffrey A. Sparks , Jackie Stratton , Dong H. Suh , Sara K. Tedeschi , Kathleen M.M. Vanni , Nina P. Paynter , and Paul M Ridker Metrics Cited byAdverse Effects of Low-Dose MethotrexateR. Brooks Robey, MD and Clay A. Block, MD, MSLow-dose methotrexate: risk of skin cancer and GI and pulmonary AEs 17 March 2020Volume 172, Issue 6Page: 425-426KeywordsCirrhosisEnzymesFolic acidHazard ratioLiverMethotrexateRenal cancerSafetyToxicityUlcers ePublished: 18 February 2020 Issue Published: 17 March 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...