High Prevalence of Methotrexate Intolerance in Juvenile Idiopathic Arthritis Development and Validation of a Methotrexate Intolerance Severity Score
High Prevalence of Methotrexate Intolerance in Juvenile Idiopathic Arthritis Development and Validation of a Methotrexate Intolerance Severity Score
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DOI：
10.1002/art.30367
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发表时间：
2011-07-01
影响因子：
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通讯作者：
Wulffraatl, Nico M.
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文献类型：
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作者：
Bulatovic, Maja;Heijstek, Marloes W.;Wulffraatl, Nico M.
目标。设计并验证一份新的甲氨蝶呤(MTX)不耐受患者问卷，并利用该问卷确定幼年特发性关节炎(JIA)患者MTX不耐受的患病率。编制了甲氨蝶呤不耐受严重程度评分问卷，包括胃痛、恶心、呕吐、口腔酸痛和行为症状5个领域。每个领域由3个问题组成，分别是在服用MTX之前、之前和在考虑(关联性)MTX时是否出现症状。MISTH问卷在86名患者中得到了验证，方法是确定其在甲氨蝶呤不耐受患者和非甲氨蝶呤不耐受患者之间的区分能力，并以黄金标准(医生的意见)确定为不耐受患者。使用MISTER问卷调查297例JIA患者甲氨蝶呤不耐受情况。MISTER问卷能很好地区分甲氨蝶呤不耐受患者和甲氨蝶呤耐受患者。以6分为界值时，敏感性(88%)和特异性(80%)最好。297例患者中有150例(50.5%)存在甲氨蝶呤不耐受。口服甲氨蝶呤患者中，98例(44.5%)出现甲氨蝶呤不耐受，而77例静脉注射甲氨蝶呤患者中，67.5%出现药物不耐受(P=0.001)。我们的研究结果表明，MISTER问卷是诊断MTX不耐受的一个高度敏感和特异的工具，而且在JIA患者中MTX不耐受的患病率很高。接受非肠外MTX治疗的患者的不耐受发生率高于接受口服MTX治疗的患者。预见性和关联性症状的频繁出现表明经典条件作用在MTX不耐受中起着重要作用。
Objective. To design and validate a new questionnaire for identifying patients with methotrexate (MTX) intolerance, and to determine the prevalence of MTX intolerance in patients with juvenile idiopathic arthritis (JIA) using this questionnaire.Methods. The MTX Intolerance Severity Score (MISS) questionnaire was constructed, consisting of 5 domains: stomach ache, nausea, vomiting, sore mouth, and behavioral symptoms. The domains each consisted of 3 questions pertaining to the presence of a symptom upon, prior to (anticipatory), and when thinking of (associative) MTX intake. The MISS questionnaire was validated in 86 patients by determining its discriminative power between patients with and those without MTX intolerance, identified as such by a gold standard (physician's opinion). Using the MISS questionnaire, the prevalence of MTX intolerance was determined in 297 JIA patients.Results. The MISS questionnaire discriminated well between MTX-intolerant and MTX-tolerant patients. A cutoff score of 6 yielded the best sensitivity (88%) and specificity (80%). MTX intolerance was found in 150 (50.5%) of 297 patients. Of 220 patients receiving oral MTX, 98 (44.5%) experienced MTX intolerance, whereas 67.5% of 77 patients receiving parenteral MTX experienced intolerance to the drug (P = 0.001).Conclusion. Our findings indicate that the MISS questionnaire is a highly sensitive and specific tool for the diagnosis of MTX intolerance, and that there is a high prevalence of MTX intolerance among JIA patients. The prevalence of intolerance in patients receiving parenteral MTX exceeds that in patients receiving oral MTX. The frequent occurrence of anticipatory and associative symptoms suggests that classic conditioning plays an important role in MTX intolerance.