Methotrexate polyglutamates as a potential marker of adherence to long-term therapy in children with juvenile idiopathic arthritis and juvenile dermatomyositis:an observational, cross-sectional study


Introduction: Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of adherence to MTX is important. The present study demonstrates the feasibility of using methotrexate polyglutamates (MTXPGs) as a biomarker to measure adherence to MTX treatment in children with JIA and JDM. Methods: Data were collected prospectively from a cohort of 48 children (median age 11.5 years) who received oral or subcutaneous (SC) MTX therapy for JIA or JDM. Dried blood spot samples were obtained from children by finger pick at the clinic or via self- or parent-led sampling at home, and they were analysed to determine the variability in MTXPG concentrations and assess adherence to MTX therapy. Results: Wide fluctuations in MTXPG total concentrations (>2.0-fold variations) were found in 17 patients receiving stable weekly doses of MTX, which is indicative of nonadherence or partial adherence to MTX therapy. Age (P = 0.026) and route of administration (P = 0.005) were the most important predictors of nonadherence to MTX treatment. In addition, the study showed that MTX dose and route of administration were significantly associated with variations in the distribution of MTXPG subtypes. Higher doses and SC administration of MTX produced higher levels of total MTXPGs and selective accumulation of longer-chain MTXPGs (P < 0.001 and P < 0.0001, respectively). Conclusions: Nonadherence to MTX therapy is a significant problem in children with JIA and JDM. The present study suggests that patients with inadequate adherence and/or intolerance to oral MTX may benefit from SC administration of the drug. The clinical utility of MTXPG levels to monitor and optimise adherence to MTX in children has been demonstrated. Trial registration: ISRCTN Registry identifier: ISRCTN93945409. Registered 2 December 2011.

Publication DOI:
Divisions: College of Health & Life Sciences > Aston Pharmacy School
Additional Information: © 2015 Hawwa et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated. Funding: Arthritis Research UK (19421); Great Ormond Street Children’s Charity (V1304); Arthritis Research UK (grant 20164) and the National Institute for Health Research – funded Biomedical Research Centre Great Ormond Street Hospital NHS Foundation Trust.
Uncontrolled Keywords: Rheumatology,Immunology,Immunology and Allergy
Publication ISSN: 1478-6362
Last Modified: 25 Mar 2024 08:16
Date Deposited: 09 Nov 2015 15:15
Full Text Link: http://www.arth ... ontent/17/1/295
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2015-10-22
Authors: Hawwa, Ahmed F.
AlBawab, AbdelQader Q.
Rooney, Madeleine
Wedderburn, Lucy R.
Beresford, Michael W.
McElnay, James C.



Version: Published Version

License: Creative Commons Attribution

Export / Share Citation


Additional statistics for this record