Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/96372
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Type: Journal article
Title: The role and utility of measuring red blood cell methotrexate polyglutamate concentrations in inflammatory arthropathies - a systematic review
Author: Mohamed, H.
Sorich, M.
Kowalski, S.
McKinnon, R.
Proudman, S.
Cleland, L.
Wiese, M.
Citation: European Journal of Clinical Pharmacology, 2015; 71(4):411-423
Publisher: Springer-Verlag
Issue Date: 2015
ISSN: 0031-6970
1432-1041
Statement of
Responsibility: 
Hamid J. Mohamed, Michael J. Sorich, Stefan M. Kowalski, Ross McKinnon, Susanna M. Proudman, Leslie Cleland, Michael D. Wiese
Abstract: PURPOSE: Evidence regarding the relationship between red blood cell methotrexate polyglutamate concentration and response to treatment and adverse drug reactions in patients using methotrexate for inflammatory arthropathies is complex and in some respects appears conflicting. Accordingly, we undertook a systematic analysis of available evidence to determine the clinical utility of dosing methotrexate to a target red blood cell methotrexate polyglutamate concentration. METHODS: A systematic literature review was conducted to identify all studies that had reported an association between red blood cell methotrexate polyglutamate concentration and disease activity or adverse drug reactions in users of methotrexate for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis or psoriatic arthritis. RESULTS: No randomised controlled trials were identified. Thirteen studies (ten in patients with rheumatoid arthritis and three in patients with juvenile idiopathic arthritis) were identified. All studies evaluated an association between red blood cell methotrexate polyglutamate concentration and response to treatment, and eight evaluated an association with toxicity. Eight studies identified lower disease activity with at least one higher red blood cell methotrexate polyglutamate concentration, although there was at least moderate potential for bias in all of these studies. Relatively large increases in concentration appeared to be required to produce a meaningful reduction in disease activity. Only one study identified an association between red blood cell methotrexate polyglutamate concentration and methotrexate-induced side effects, although studies were likely underpowered to detect this type of association. CONCLUSIONS: The manner in which data were presented in the included studies had many limitations that hampered its conclusive assessment, but red blood cell methotrexate polyglutamate concentrations appear to be a potentially useful guide to treatment in patients with inflammatory arthropathies, but the specific polyglutamate that should be monitored and how monitoring could be integrated into treat-to-target approaches should be clarified before it can be routinely implemented.
Keywords: Methotrexate polyglutamates; Rheumatoid arthritis; Juvenile idiopathic arthritis; Concentration-targeted dosing; Intracellular drug concentration; Personalised medicine
Description: First online: 18 February 2015
Rights: © Springer-Verlag Berlin Heidelberg 2015
RMID: 0030023624
DOI: 10.1007/s00228-015-1819-x
Appears in Collections:Medicine publications

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