Dupont-Lucas Claire, Grandjean-Blanchet Charlotte, Leduc Bertrand, Tripcovici Martina, Larocque Christine, Gervais France, Jantchou Prévost, Amre Devendra, Deslandres Colette
*Department of Pediatric Gastroenterology, Hepatology and Nutrition, Sainte Justine Hospital, Montreal, Quebec, Canada; †Sainte Justine Research Centre, Sainte Justine Hospital, Montreal, Quebec, Canada; and ‡Université de Montréal, Montreal, Quebec, Canada.
Inflamm Bowel Dis. 2017 Feb;23(2):298-303. doi: 10.1097/MIB.0000000000001014.
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.
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.
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.
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.
甲氨蝶呤（MTX）不耐受被定义为在MTX给药之前或之后出现的胃肠道和行为症状，这些症状可能导致治疗中断。本研究的目的是使用在风湿病学中开发的甲氨蝶呤不耐受严重程度评分来确定儿科炎症性肠病（IBD）中甲氨蝶呤不耐受的患病率，并确定甲氨蝶呤不耐受的危险因素。
邀请在圣贾斯汀医院IBD诊所就诊的儿科IBD患者，这些患者在2004年至2016年间因IBD接受过MTX治疗且仍在积极使用MTX，填写甲氨蝶呤不耐受严重程度评分问卷。使用≥6分的临界值来定义MTX不耐受，预期、关联或行为项目至少得1分。
在102例儿科IBD患者中，32例（31%）报告有MTX不耐受症状。使用多变量逻辑回归模型，与有MTX不耐受症状相关的因素为女性（比值比4.31[95%置信区间，1.37 - 13.60]，P = 0.01）、在问卷调查时接受高于20 mg/周的MTX剂量（比值比4.06[95%置信区间，1.30 - 12.70]，P = 0.02）以及根据医生整体评估有活动性疾病（比值比3.44[95%置信区间，1.15 - 10.26]，P = 0.03）。预防性使用止吐药和叶酸并不能预防MTX不耐受症状。
MTX不耐受症状在儿科IBD中很常见。甲氨蝶呤不耐受严重程度评分问卷有助于更好地识别这些症状。危险因素的识别可能对治疗的成功具有重要意义。
