Cash Brooks D, Lacy Brian E, Watton Cheryl, Schoenfeld Philip S, Weissman Darren
Department of Gastroenterology, Hepatology and Nutrition, University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 4.234, Houston, TX 77030, USA.
Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA.
Therap Adv Gastroenterol. 2021 Apr 10;14:17562848211001725. doi: 10.1177/17562848211001725. eCollection 2021.
Eluxadoline, a United States Food and Drug Administration (FDA)-approved treatment for irritable bowel syndrome with diarrhea (IBS-D), underwent a change to its US prescribing information on 21 April 2017, contraindicating it in patients without a gallbladder due to increased risk of pancreatitis. This study aimed to elucidate the potential role of eluxadoline's label change on the number of reported spontaneous adverse events (AEs) of pancreatitis.
A pharmacovigilance database (Oracle Argus) was searched for eluxadoline use and spontaneously reported pancreatitis cases from 1 January 2016 to 30 June 2018. Pancreatitis cases were reported as a proportion of the total number of reported AE cases in the safety database. The FDA's adverse event reporting system (AERS) was also interrogated for cases of pancreatitis concomitantly reported with eluxadoline use.
In patients who received eluxadoline, 273 reported cases of pancreatitis were recorded (total AEs = 2191; 12.5%). When known, 28.2% of patients reporting pancreatitis had intact gallbladders (49/174). Eluxadoline was withdrawn in 97.5% of cases, with 87.1% of patients improving or recovered at time of reporting. Importantly, the reporting proportion of pancreatitis cases decreased from 14.4% to 8.9% post label change. Findings were supported by the AERS results, which demonstrated a decrease in reporting proportion from 21.2% to 12.8%.
While cautious interpretation is warranted, post-marketing data indicate that the contraindication of eluxadoline in patients without a gallbladder led to reduced reported cases of pancreatitis, with no additional reports of moderately severe or severe cases. Eluxadoline is a safe and well-tolerated treatment option for IBS-D when used according to the label.
埃卢卡多林是一种经美国食品药品监督管理局（FDA）批准用于治疗腹泻型肠易激综合征（IBS-D）的药物，其美国处方信息于2017年4月21日发生变更，因胰腺炎风险增加，禁止在无胆囊患者中使用。本研究旨在阐明埃卢卡多林标签变更对报告的胰腺炎自发不良事件（AE）数量的潜在影响。
检索药物警戒数据库（甲骨文阿格斯）中2016年1月1日至2018年6月30日期间埃卢卡多林的使用情况及自发报告的胰腺炎病例。胰腺炎病例报告为安全数据库中报告的AE病例总数的比例。还对FDA的不良事件报告系统（AERS）中与埃卢卡多林使用相关的胰腺炎病例进行了查询。
在接受埃卢卡多林治疗的患者中，记录到273例报告的胰腺炎病例（总AE数=2191；12.5%）。在已知情况的患者中，报告胰腺炎的患者中有28.2%胆囊完好（49/174）。97.5%的病例中埃卢卡多林被停用，87.1%的患者在报告时病情改善或康复。重要的是，标签变更后胰腺炎病例的报告比例从14.4%降至8.9%。AERS结果支持了这一发现，该结果显示报告比例从21.2%降至12.8%。
尽管需要谨慎解读，但上市后数据表明，埃卢卡多林在无胆囊患者中的禁忌导致报告的胰腺炎病例减少，且无中度或重度病例的额外报告。按照标签使用时，埃卢卡多林是IBS-D的一种安全且耐受性良好的治疗选择。
