Abstract
BackgroundMethotrexate (MTX) is an effective and safe drug in the treatment of juvenile idiopathic arthritis (JIA). Despite its safety, MTX-related gastrointestinal adverse effects before and after MTX administration, termed MTX intolerance, occur frequently, leading to non-compliance and potentially premature MTX termination. The aim of this study was to construct a risk model to predict MTX intolerance.MethodsIn a prospective JIA cohort, clinical variables and single nucleotide polymorphisms were determined at MTX start. The Methotrexate Intolerance Severity Score was employed to measure MTX intolerance in the first year of treatment. MTX intolerance was most prevalent at 6 or 12 months after MTX start, which was defined as the outcome for the prediction model. The model was developed in 152 patients using multivariable logistic regression analysis and subsequently internally validated using bootstrapping.ResultsThe prediction model included the following predictors: JIA category, antinuclear antibody, parent/patient assessment of pain, Juvenile Arthritis Disease Activity Score-27, thrombocytes, alanine aminotransferase and creatinine. The model classified 77.5% of patients correctly, and 66.7% of patients after internal validation by bootstrapping. The lowest predicted risk of MTX intolerance was 18.9% and the highest predicted risk was 85.9%. The prediction model was transformed into a risk score (range 0–17). At a cut-off of ≥6, sensitivity was 82.0%, specificity 56.1%, positive predictive value was 58.7% and negative predictive value 80.4%.ConclusionsThis clinical prediction model showed moderate predictive power to detect MTX intolerance. To develop into a clinically usable tool, it should be validated in an independent cohort and updated with new predictors. Such an easy-to-use tool could then assist clinicians in identifying patients at risk to develop MTX intolerance, and in turn to monitor them closely and intervene timely in order to prevent the development of MTX intolerance.Trial registrationISRCTN register, www.isrctn.com, ISRCTN13524271
Highlights
Methotrexate (MTX) is an effective and safe drug in the treatment of juvenile idiopathic arthritis (JIA)
Baseline characteristics of the prediction model cohort The prediction model was constructed in 152 patients
Intolerant and tolerant patients did not differ regarding the proportion of MTX re-starters, MTX dose, route of administration, concomitant medication use or disease activity (Juvenile Arthritis Disease Activity score [juvenile arthritis disease activity score (JADAS)-27]) at 6 and 12 months after MTX start
Summary
Methotrexate (MTX) is an effective and safe drug in the treatment of juvenile idiopathic arthritis (JIA). MTX-related gastrointestinal adverse effects before and after MTX administration, termed MTX intolerance, occur frequently, leading to non-compliance and potentially premature MTX termination. In JIA, methotrexate (MTX) is the cornerstone treatment, due to its efficacy and safety Serious adverse effects such as hepatotoxicity and bone marrow suppression occur rarely [3]. JIA patients experience anticipatory adverse effects, occurring before MTX administration (at the sight of MTX), and associative adverse effects, occurring when thinking of MTX administration (its colour or smell) [4,5,14] These adverse effects are thought to be a result of classical conditioning to the abovementioned physical symptoms experienced after MTX intake [14]. Such consequences could be avoided, if the development of MTX intolerance is prevented
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