甲氨蝶呤在49例克罗恩病患者维持缓解治疗中的疗效和耐受性分析

Efficacy and tolerance of methotrexate in maintenance of remission in 49 patients with Crohn′s disease

目的分析甲氨蝶呤治疗 CD 维持缓解期患者的疗效和耐受性。方法纳入2012年6月至2015年8月就诊并将甲氨蝶呤作为维持缓解期主要治疗用药的49例 CD 患者，分析其既往用药情况，甲氨蝶呤维持缓解治疗的疗效、使用剂量和不良反应等，分析诱导缓解方式对疾病复发的影响。统计学分析采用 t 检验或卡方检验。结果49例 CD 患者中，采用糖皮质激素诱导缓解治疗者34例（69．4％），采用英 夫 利 西 单 克 隆 抗 体 诱 导 缓 解 治 疗 者 9例 （18．4％），经过手术治疗缓解者6例（12．2％）。44例曾使用过硫唑嘌呤的患者，其中位治疗时间为1个月，使用剂量为（42．0±14．8）mg／d；停药原因以 WBC 计数下降最常见，占81．8％（36／44）。至随访截点，49例 CD 患者中46例尚在口服甲氨蝶呤，其中位治疗时间为16个月，每周剂量为（12．7±2．0）mg；临床稳定31例（67．4％），临床复发15例（32．6％）；克罗恩病活动指数（CDAI）平均值为（123．5±66．6）分。临床稳定组每周剂量为（12．5±2．1）mg，临床复发组每周剂量为（13．0± 1．7）mg，两组差异无统计学意义（t ＝0．802，P ＝0．426）。糖皮质激素诱导缓解组的复发率[41．2％（14／34）]高于英夫利西单克隆抗体＋手术诱导缓解组（1／15），差异有统计学意义（χ2＝5．177，P ＝0．023）。不良反应以胃肠道反应[26．5％（13／49）]、肝功能损伤[20．4％（10／49）]和 WBC 计数下降[12．2％（6／49）]常见，3例因无法耐受不良反应而停药。结论甲氨蝶呤作为 CD 维持缓解治疗的二线免疫抑制剂，其疗效确切，耐受性较好，在 CD 患者的漫长病程中可作为重要的药物选择。

Objective To analyze the efficacy and tolerance of methotrexate（MTX）in remission maintenance of Crohn′s disease （CD）.Methods From June 2012 to August 2015 ,49 CD patients who received MTX as mainly treatment medication to maintain remission were enrolled.The pre-medication history,efficacy,dosage and side effects of MTX were analyzed.The effects of inducing strategy on disease recurrence were analyzed.Chi-square test and t test were used for statistical analysis.Results Among the 49 patients,34 （69.4%）received steroids for remission inducing,nine （18.4%）received infliximab for remission inducing and six （12.2%）achieved remission after operation.In the 44 patients treated with azathioprine （AZA）before,the median treatment time was one month and the dosage for withdrawal of AZA was （42.0 ± 14.8）mg/d.The most common reason was leucopenia （81 .8%, 36/44）.Till the time point of follow-up,46 of the 49 CD patients still took MTX orally with a median treatment time of 16 months,and the weekly dosage was （12.7 ±2.0）mg.Thirty-one cases （67.4%） achieved clinical stability,while 15 cases （32.6%）underwent clinical recurrence.The median Crohn′s disease activity index （CDAI）was 123.5 ± 66.6.The weekly dosage of clinical stability group was （12.5 ±2.1）mg,and that of clinical recurrence group was （13.0 ±1 .7 ）mg,there was no statistically＆amp;nbsp;significant difference between the two groups （t =0.802,P =0.426 ）.The recurrence rate of steroids-induced remission group was 41 .2% （14/34 ）,which was higher than that of infliximab and surgery-induced remission group （1/15）,and the differnce was statistically significant （χ2 =5 .177,P =0.023 ）. The common side effects were gastrointestinal reaction （26.5 %, 13/49 ）, impaired liver function （20.4%,10/49）and leukopenia （12.2%,6/49）.Only three cases could not tolerate the side effects and underwent medication withdrawal.Conclusions As a second-line immunosuppressant for maintanence remission in CD,MTX is effective and well-tolerated in patients.So it can be an important option during the long course of CD.