Prediction of response to methotrexate in rheumatoid arthritis

ABSTRACT

Introduction: Methotrexate (MTX) is the first-line disease-modifying drug of choice in controlling active inflammation of the synovium that characterises rheumatoid arthritis, a chronic autoimmune inflammatory condition. However, many patients do not respond to treatment with MTX or cannot tolerate the medication. Pre-treatment characteristics that predict response to MTX are, therefore, of particular interest and potential clinical utility.

Areas covered: This narrative review seeks to cover various genotypic and phenotypic characteristics that have been investigated as predictors of treatment response to MTX in RA. Ovid Medline searches (1946 to January 2018) were carried out for ‘methotrexate’ and ‘rheumatoid arthritis’, in combination with relevant terms. All papers identified were English language, with abstracts. Relevant references were also reviewed.

Expert commentary: Despite the introduction of biologic medication and targeted therapies, MTX is likely to remain the mainstay of RA treatment, largely due to its much cheaper cost. Development of a multifactorial predictive algorithm for response to MTX may be of clinical utility, as well as routine MTX drug level testing to improve medication adherence and persistence.

KEYWORDS:

• Biomarkers
• genetics
• methotrexate
• rheumatoid arthritis
• treatment response

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

We thank the Medical Research Council (MRC) and Arthritis Research UK (ARUK) for their joint funding of the Maximising Therapeutic Utility in Rheumatoid Arthritis (MATURA) study [grant codes MR/K015346/1 and 20670, respectively]. Support for this work was also provided by the NIHR Manchester BRC, Arthritis Research UK [grant reference 20385], and an NIHR Senior Investigator award to A Barton. The views expressed are those of the authors and not necessarily those of the NHS, National Institute for Health Research (NIHR) or the Department of Health.