Vedolizumab use in patients with inflammatory bowel diseases undergoing surgery:clinical trials and post-marketing experience  

维多株单抗在炎症性肠病手术患者中的应用:临床试验和上市后评估

作　　者：Bo Shen Aimee Blake Karen Lasch Michael Smyth Fatima Bhayat 

机构地区：[1]Center for Inflammatory Bowel Disease,Digestive Disease and Surgery Institute,Cleveland Clinic,Cleveland,OH,USA [2]Global Patient Safety Evaluation,Takeda Pharmaceuticals International Co.,Cambridge,MA,USA [3]US Medical Office,Takeda Pharmaceuticals USA Inc.,Deerfield,IL,USA [4]Global Medical Affairs,Takeda Development Centre Europe Ltd,London,UK [5]Kyowa Kirin International plc,Chertsey,UK

出　　处：《Gastroenterology Report》2019年第5期322-330,I0001,共10页胃肠病学报道（英文）

基　　金：This work was supported by Takeda Pharmaceutical Company Ltd.

摘　　要：Background:Patients with inflammatory bowel diseases frequently require surgery,but immunotherapies used in disease management may increase the risk of post-operative complications.We investigated frequencies of post-operative complications in patients who received vedolizumab—a gut-selective antibody approved for the treatment of moderately to severely active ulcerative colitis and Crohn’s disease—in clinical-trial and post-marketing settings.Methods:This post hoc analysis of safety data from GEMINI 1,GEMINI 2,and long-term safety studies included patients who had had colectomy or bowel surgery/resection.Data from the post-marketing Vedolizumab Global Safety Database were also analysed(data cutoff point:19 May 2016).Adverse events relating to post-operative complications were identified using Medical Dictionary for Regulatory Activities preferred terms.Results:Of 58 total surgeries in patients included in GEMINI 1 and GEMINI 2,post-operative complications were reported for 3/51 vedolizumab-treated patients(5.9%)and 1/7 placebo-treated patients(14.3%).In the long-term safety study,157/2,243 patients(7%)had colectomy or bowel surgery/resection;of these 157 patients who underwent surgery,11(7%)experienced a post-operative complication.Median time between last pre-operative vedolizumab dose and surgery was 23 days in GEMINI 1,20 days in GEMINI 2,and 39–40 days in the long-termsafety study.In the post-marketing setting,based on data covering approximately 46,978 patient-years of vedolizumab exposure,post-operative complications were reported in 19 patients.Conclusions:In clinical trials,complications of colectomy and bowel surgery/resection appeared infrequent,with minimal difference between vedolizumab and placebo.The frequency of post-operative complications in the post-marketing setting appears low.背景:炎症性肠病(IBD)患者常需手术治疗,但其长期接受免疫治疗会增加术后并发症的风险。本研究从临床试验和上市后应用两个层面,调查接受维多株单抗(一种已被批准用于中重度IBD的肠道选择性抗体)治疗的炎症性肠病患者术后并发症的发生频率。方法:本研究基于GEMINI 1、GEMINI 2两项临床试验的安全性数据以及长期安全性研究数据进行析因分析,上述研究对象为接受结肠切除术或小肠切除术的IBD患者。同时,本研究也对维多株单抗全球安全性数据库进行上市后分析(截止日期:2016年5月19日)。使用Medical Dictionary for Regulatory Activities推荐术语对术后并发症相关的不良事件进行定义。结果:GEMINI 1和GEMINI 2研究共计纳入58例手术病例,维多株单抗治疗者和安慰剂对照者术后并发症发生率分别为5.9%(3/51)和14.3%(1/7)。在长期安全性研究中,2,243例病例中有157例(7%)接受了结肠或小肠切除手术,其中11例(7%)出现术后并发症。维多株单抗末次服药与手术的中位间隔时间,在GEMINI 1试验中为23天,在GEMINI 2试验中为20天,在长期安全性研究中为39-40天。上市后,基于46,978例维多株单抗服用者的分析显示,仅19例病例报道了术后并发症。结论:在临床试验中,结肠或小肠切除术后并发症并不常见,其在维多株单抗与安慰剂对照之间的差异甚微。在上市后分析中,术后并发症发生频率似乎非常低。

关 键 词：inflammatory bowel disease colorectal surgery vedolizumab 

分 类 号：R574[医药卫生—消化系统]