甲氨蝶呤治疗难治性克罗恩病的疗效及安全性分析

The efficacy and safety of methotrexate in refractory Crohn＇s disease

目的分析总结甲氨蝶呤（MTX）治疗难治性克罗恩病（CD）的疗效及安全性。方法回顾性分析2004年6月至2012年12月于中山大学附属第一医院炎症性肠病中心随访的经MTX治疗的难治性CD的疗效及副作用。结果共纳入35例难治性CD患者，其中23例为硫唑嘌呤（AZA）/6．巯基嘌呤（6-MP）不耐受者，6例为AZA/6．MP治疗无效，19例为糖皮质激素（简称激素）依赖患者。MTX治疗12周[15（5～20）mg/周]时评估其疗效，临床应答率为80％（28/35），其中临床缓解18例（51．4％），临床改善10例（28．6％），治疗前后的克罗恩病活动指数（CDAI）中位值分别为99．2（75．8，174．7）分和61．5（36．0，106．6）分。MTX每周用药剂量中位值为15（5～20）mg，中位治疗时间6．0（0．5～53．0）个月，累积剂量中位值为480（20～2615）mg。26例MTX合并使用激素的患者中，21例停用激素，中位停用时间为10（6～20）周。副作用方面：12例（34．3％）患者出现了轻微的副作用，但都可在停药后缓解。结论MTX治疗难治性CD有效，可减少激素的用量，其副作用相对较小，可以耐受。

Objective To assess the efficacy and safety of methotrexate（MTX） on refractory Crohn＇s disease（CD）. Methods A total of 35 consecutive refractory CD patients in the First Affiliated Hospital of Sun Yat-Sen University treated with MTX were retrospectively analyzed. Clinical data from June 2004 to December 2012 were collected from the database of inflammatory bowel disease （IBD） center. Clinical responses and drug side effects were recorded and analyzed. Results Thirty-five refractory CD patients were identified including 23 cases intolerant to azathioprine （ AZA ）/6-mercaptopurine （ 6-MP ）, six cases ineffective to AZA/6-MP, 19 cases dependent on steroid. After treatment of MTX for 12 weeks [ 15（5-20） mg/week~, a clinical response was obtained in 80% patients （28/35）, including 51.4% （18/35） in remission and 28.6% （10/35） in improvement. The median Crohn＇s disease activity index （CDAI） scores at the onset and 12 weeks after MTX therapy were 99.2 （75.8,174.7） and 61.5 （36.0, 106.6） respectively. The median single dose and duration of MTX were 15（5-20） rag/week and 6. 0（0. 5-53. O） months respectively. The median cumulative dose was 480 （20-2615） mg. Among the 26 patients dependent on steroid, 21 achieved discontinuation of steroid with a median time of 10 （6-20） weeks after treatment of MTX. Side effects were recorded in 12 patients（34. 3% ）, but usually mild and improved after drug with drawal. Conclusions MTX is an effective and steroid-sparing agent for refractory CD. Side effects of MTX are mild and tolerable.