Lacy Brian E, Harris Lucinda A, Chang Lin, Lucak Susan, Gutman Catherine, Dove Leonard S, Covington Paul S, Lembo Anthony
Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Mayo Clinic, Scottsdale, AZ, USA.
Therap Adv Gastroenterol. 2019 Apr 15;12:1756284819841290. doi: 10.1177/1756284819841290. eCollection 2019.
Irritable bowel syndrome with diarrhea (IBS-D) is a prevalent gastrointestinal (GI) disorder with a varied presentation, often overlapping with other GI and non-GI disorders. Eluxadoline is a locally active mixed µ- and κ-opioid receptor agonist and δ-opioid receptor antagonist approved for the treatment of IBS-D in adults. As IBS-D is a heterogeneous disease, factors such as patient demographics, symptom severity, and symptom pattern history can potentially inform treatment selection.
Here, we report additional prospectively planned analyses of two large double-blind, placebo-controlled studies (IBS-3001 and IBS-3002) enrolling patients meeting Rome III criteria for IBS-D. Patients were randomized 1:1:1 to receive placebo or eluxadoline 75 mg or 100 mg twice daily. Efficacy (abdominal pain, stool consistency, and composite, simultaneous improvement in both) and safety were assessed for prospectively defined patient subgroups stratified by age, sex, race, presence of comorbidities, and baseline disease characteristics.
Across all age, sex, race, comorbidity, and disease characteristic subgroups, a greater proportion of patients were composite responders with both eluxadoline doses as compared with placebo, including patients with a history of depression or a history of gastroesophageal reflux disease. Among patients aged ⩾65 years, a greater proportion of patients receiving eluxadoline 75 mg were composite, abdominal pain, and stool consistency responders compared with those receiving 100 mg. The proportion of patients with at least one adverse event was slightly higher in patients aged ⩾65 years and also in female patients.
This analysis suggests that eluxadoline is effective in treating IBS-D across a range of commonly encountered patient types. In contrast to the overall population, patients aged ⩾65 years demonstrated a greater proportion of responders at the lower approved 75 mg eluxadoline dose.
腹泻型肠易激综合征（IBS - D）是一种常见的胃肠道（GI）疾病，表现多样，常与其他胃肠道和非胃肠道疾病重叠。埃卢多啉是一种局部起作用的μ和κ阿片受体激动剂及δ阿片受体拮抗剂，已被批准用于治疗成人IBS - D。由于IBS - D是一种异质性疾病，患者人口统计学特征、症状严重程度和症状模式史等因素可能有助于指导治疗选择。
在此，我们报告了对两项大型双盲、安慰剂对照研究（IBS - 3001和IBS - 3002）进行的额外前瞻性计划分析，这些研究纳入了符合罗马III标准的IBS - D患者。患者按1:1:1随机分组，接受安慰剂或每日两次75毫克或100毫克的埃卢多啉治疗。对按年龄、性别、种族、合并症情况和基线疾病特征分层的前瞻性定义患者亚组评估疗效（腹痛、大便性状及两者同时改善的综合情况）和安全性。
在所有年龄、性别、种族、合并症和疾病特征亚组中，与安慰剂相比，接受两种剂量埃卢多啉治疗的患者中复合应答者的比例更高，包括有抑郁症病史或胃食管反流病病史的患者。在年龄≥65岁的患者中，接受75毫克埃卢多啉治疗的患者中复合、腹痛及大便性状应答者的比例高于接受100毫克治疗的患者。年龄≥65岁的患者以及女性患者中至少发生一次不良事件的患者比例略高。
该分析表明，埃卢多啉对一系列常见类型的患者治疗IBS - D有效。与总体人群不同，年龄≥65岁的患者在批准的较低剂量75毫克埃卢多啉治疗下应答者比例更高。
