沙利度胺治疗炎症性肠病的不良反应分析

Analysis of adverse drug reactions of thalidomide in treatment of inflammatory bowel disease

目的：分析炎症性肠病患者中应用沙利度胺的药物不良反应（ADR）。方法随访102例服用沙利度胺的炎症性肠病患者所有 ADR，并分析其种类、程度、发生时间及神经毒性剂量关系。结果102例患者服用沙利度胺的疗程18（8～36）个月，实际用药剂量为50（25～125）mg／d。沙利度胺累积剂量克罗恩病患者为27（6～54）g，溃疡性结肠炎患者为18（12～36）g。102例患者中有79例出现 ADR，位居前3位的依次为嗜睡52.94％（54／102）、手足麻木36.27％（37／102）和便秘30.39％（31／102），其中60.75％（48／79）为轻度，16.45％（13／79）因 ADR 停药。出现外周神经不良反应与未出现患者在服用沙利度胺最大剂量上无明显差异（P ＞0.05），而与累积剂量相关（P ＜0.05）。结论沙利度胺在炎症性肠病治疗过程中 ADR 发生率高，但大多数为轻度，且 ADR 在停药后可逆转，可在密切监测下安全用药。

Objective To analyze the adverse drug reactions （ADR） of thalidomide in the treatment of inflammatory bowel disease. Methods All ADR in patients with inflammatory bowel disease were collected after thalidomide treatment during follow-up. The type, severity, time of incidence and the neurotoxicity-dosage relationship were investigated. Results One hundred and two patients were treated with thalidomide. The mean duration of thalidomide treatment was 18 （8-36） months. The mean actual drug dose was 50 （25-125） mg per day. The cumulative dose of thalidomide was 27 （6-54） g in patients with Crohn’s disease,and 18 （12-36） g in those with ulcerative colitis. In total, 79 of 102 cases presented with ADR. The most common ADR were somnolence 52.94% （54/102）, limb numbness 36.27% （37/102） and constipation 30.39% （31/102）. In total, 60.75% （48/79） of patients had mild ADR and 16.45% （13/79） discontinued the use of medication due to the incidence of ADR. The maximal dosage of thalidomide did not significantly differ between patients with and without neuropathy （ P 〉 0. 05 ） , whereas it was correlated with the cumulative dose （P 〈 0. 05 ） . Conclusions The incidence of ADR of thalidomide in treating inflammatory bowel disease is high. A majority of ADR are mild and can be restored after terminating the use of thalidomide. Thalidomide ad-ministration is a safe therapy of inflammatory bowel disease under close monitoring.