Abstract
Methotrexate (MTX) is the central drug in the management of rheumatoid arthritis (RA) and other immune mediated inflammatory diseases. It is widely used either in monotherapy or in association with other synthetic and biologic disease modifying anti-rheumatic drugs (DMARDs). Although comprehensive clinical experience exists for MTX and synthetic DMARDs, to date it has not been possible to preview correctly whether or not a patient will respond to treatment with these drugs. Predicting response to MTX and other DMARDs would allow the selection of patients based on their likelihood of response, thus enabling individualized therapy and avoiding unnecessary adverse effects and elevated costs. However, studies analyzing this issue have struggled to obtain consistent, replicable results and no factor has yet been recognized to individually distinguish responders from nonresponders at treatment start. Variables possibly influencing drug effectiveness may be disease-, patient- or treatment-related, clinical or biological (genetic and nongenetic). In this review we summarize current evidence on predictors of response to MTX and other synthetic DMARDs, discuss possible causes for the heterogeneity observed and address its translation into daily clinical practice.
Highlights
Methotrexate (MTX) is the anchor disease modifying anti-rheumatic drug (DMARD) in the management of rheumatoid arthritis (RA) and other immune mediated chronic inflammatory disorders
Conclusions and comments are based on the findings reported and discussed in the text
While some studies showed a significant association between inflammatory markers and response, usually with higher baseline values associated with weaker treatment responses, others, including large meta-analyses, do not find these variables to be good predictive markers, at least when considered independently
Summary
Methotrexate (MTX) is the anchor disease modifying anti-rheumatic drug (DMARD) in the management of rheumatoid arthritis (RA) and other immune mediated chronic inflammatory disorders. Capell et al observed that a lower ESR was related to a worse response to gold, penicillamine or SSZ [32] As a whole, these results are not sufficient to state whether ESR or CRP alone are predictive factors of response to MTX and other DMARDs. While some studies showed a significant association between inflammatory markers and response, usually with higher baseline values associated with weaker treatment responses, others, including large meta-analyses, do not find these variables to be good predictive markers, at least when considered independently. While more studies are needed to reproduce these findings, as a whole, the analysis of different SNPs in various genes involved in the response to MTX and the interactions between them seems to be a promising approach that may bring more consistency to the body of data on MTX pharmacogenetics
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