Prevalence and Risk Factors for Symptoms of Methotrexate Intolerance in Pediatric Inflammatory Bowel Disease

Background: Methotrexate (MTX) intolerance is defined as gastrointestinal and behavioral symptoms occurring before or after MTX administration that may lead to treatment discontinuation. The aim of this study was to determine prevalence of MTX intolerance in pediatric inflammatory bowel disease (IBD) using the Methotrexate Intolerance Severity Score developed in rheumatology and to identify risk factors for MTX intolerance. Methods: Patients with pediatric IBD followed in the IBD clinic of Sainte Justine Hospital who had received MTX for IBD between 2004 and 2016 and were still actively on MTX were invited to fill out the Methotrexate Intolerance Severity Score questionnaire. A cutoff score of ≥6 points was used to define MTX intolerance, with at least one point for anticipatory, associative or behavioral items. Results: Among 102 pediatric patients with IBD, 32 (31%) patients reported symptoms of MTX intolerance. Using a multivariable logistic regression model, factors that were associated with having symptoms of MTX intolerance were female sex (odds ratio 4.31 [95% confidence interval, 1.37-13.60], P = 0.01), receiving a dose of MTX higher than 20 mg/wk at the time of the questionnaire (odds ratio 4.06 [95% confidence interval, 1.30-12.70], P = 0.02), and having active disease according to Physician's Global Assessment (odds ratio 3.44 [95% confidence interval, 1.15-10.26], P = 0.03). Prophylactic prescription of antiemetics and folic acid did not prevent symptoms of MTX intolerance. Conclusions: Symptoms of MTX intolerance are frequent in pediatric IBD. The Methotrexate Intolerance Severity Score questionnaire could help better recognition of these symptoms. Identification of risk factors could have important implications for the success of treatment.