Pironi Loris, Raschi Emanuel, Sasdelli Anna Simona
Alma Mater Studiorum -University of Bologna, Department of Medical and Surgical Sciences, Italy.
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Centre for Chronic Intestinal Failure - Clinical Nutrition and Metabolism Unit, Italy.
Expert Opin Drug Saf. 2021 Dec;20(12):1501-1513. doi: 10.1080/14740338.2021.1940947. Epub 2021 Jun 19.
Short bowel syndrome (SBS) is a rare, highly disabling, life-threatening condition due to extensive intestinal resections, characterized by diarrhea, malabsorption, and malnutrition. SBS is the main cause of intestinal failure (SBS-IF). The primary therapy for SBS-IF is intravenous supplementation (IVS) of nutrients. The pharmacological therapy aims to improve the remnant bowel function, leading to the decrease of IVS requirement.
This review provides a safety perspective and discusses unmet clinical needs on pharmacotherapy for SBS, ranging from symptomatic agents traditionally used off-label to manage hypersecretion and diarrhea, to curative drugs with selective intestinotrophic properties. Real-world evidence on symptomatic drugs is lacking. Data on teduglutide - the first-in-class glucagon-like peptide-2 (GLP-2) receptor agonist approved in SBS - are mainly derived from clinical trials, with several unsettled safety issues, including the risk of malignancies.
Defining the long-term safety of drugs used for SBS is a priority; a unified list of commonly used drugs with consolidated proof of effectiveness is needed to harmonize the symptomatic pharmacological approach to SBS. GLP-2 receptor agonists are a promising curative pharmaco-therapeutic approach, although long-term safety and effectiveness deserve further real-world assessment. Pharmacovigilance and global data sharing are crucial to support safe prescribing in SBS.
短肠综合征(SBS)是一种因广泛肠道切除导致的罕见、严重致残且危及生命的疾病,其特征为腹泻、吸收不良和营养不良。SBS是肠衰竭(SBS-IF)的主要原因。SBS-IF的主要治疗方法是静脉补充(IVS)营养物质。药物治疗旨在改善残余肠道功能,从而减少IVS需求。
本综述提供了一个安全性视角,并讨论了SBS药物治疗方面未满足的临床需求,范围从传统上用于治疗分泌过多和腹泻的超说明书使用的对症药物,到具有选择性肠营养特性的治疗性药物。缺乏关于对症药物的真实世界证据。替度鲁肽——首个获批用于SBS的胰高血糖素样肽-2(GLP-2)受体激动剂——的数据主要来自临床试验,存在一些尚未解决的安全问题,包括恶性肿瘤风险。
确定用于SBS的药物的长期安全性是当务之急;需要一份具有确凿有效性证据的常用药物统一清单,以协调SBS的对症药物治疗方法。GLP-2受体激动剂是一种有前景的治疗性药物方法,尽管其长期安全性和有效性值得进一步的真实世界评估。药物警戒和全球数据共享对于支持SBS的安全处方至关重要。