Salem George, Ding Kai, Sakuraba Atsushi, Cohen Russell
Department of Internal Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
J Investig Med. 2021 Feb 23. doi: 10.1136/jim-2020-001699.
Several published studies have evaluated the safety and effectiveness of oral and intravenous tacrolimus for the management of patients with inflammatory bowel disease (IBD). However, little is known about the effectiveness of topical tacrolimus in this patient population. The aim of this systematic review was to evaluate the current state of literature to evaluate the safety and effectiveness of rectal administration of topical tacrolimus, in the form of suppository, ointment, and/or enema in patients with ulcerative proctitis, perianal Crohn's disease (CD), and chronic refractory pouchitis. Electronic database searches were conducted in international databases since their inception until February 2020. Study subjects were categorized into three groups: topical tacrolimus for patients with proctitis, perianal CD, and chronic refractory pouchitis. The primary end point of this study was the remission rate. Secondary end points were response rate and the incidence of AEs. Eleven studies were included in the final assessment in this systematic review. This provided information from 188 patients. Tacrolimus was administered topically as suppositories, ointment, or enema. Clinical remission was achieved in 57.1%, 57.14%, and 70.0% in patients with proctitis, fistulizing perianal CD, and chronic pouchitis. The most commonly reported side effect was perianal itching and burning. Reversible nephrotoxicity occurred in a single patient. No clear correlation was found between blood levels and clinical outcomes. Topical tacrolimus is effective for a subset of patients with IBD. The adverse effects were minimal and tolerable. Well-designed randomized clinical trials are warranted to establish the appropriate dose and administration method.
多项已发表的研究评估了口服和静脉注射他克莫司治疗炎症性肠病（IBD）患者的安全性和有效性。然而，对于局部应用他克莫司在该患者群体中的有效性知之甚少。本系统评价的目的是评估现有文献，以评价在溃疡性直肠炎、肛周克罗恩病（CD）和慢性难治性贮袋炎患者中，以栓剂、软膏和/或灌肠剂形式直肠给药局部用他克莫司的安全性和有效性。自各国际数据库建立至2020年2月进行了电子数据库检索。研究对象分为三组：用于直肠炎、肛周CD和慢性难治性贮袋炎患者的局部用他克莫司。本研究的主要终点是缓解率。次要终点是反应率和不良事件发生率。11项研究纳入了本系统评价的最终评估。这提供了来自188例患者的信息。他克莫司以栓剂、软膏或灌肠剂的形式局部给药。直肠炎、肛瘘性肛周CD和慢性贮袋炎患者的临床缓解率分别为57.1%、57.14%和70.0%。最常报告的副作用是肛周瘙痒和烧灼感。1例患者出现可逆性肾毒性。未发现血药浓度与临床结局之间有明确相关性。局部用他克莫司对一部分IBD患者有效。不良反应轻微且可耐受。有必要进行精心设计的随机临床试验以确定合适的剂量和给药方法。
