Predictors of response to low-dose amitriptyline for irritable bowel syndrome and efficacy and tolerability according to subtype: post hoc analyses from the ATLANTIS trial

IF 23 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut Pub Date : 2025-01-25 DOI:10.1136/gutjnl-2024-334490

Alexandra Wright-Hughes, Pei-Loo Ow, Sarah L Alderson, Matthew J Ridd, Robbie Foy, Felicity L Bishop, Matthew Chaddock, Catherine Fernandez, Elspeth A Guthrie, Delia P Muir, Christopher A Taylor, Amanda J Farrin, Hazel A Everitt, Alexander C Ford

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Abstract

Background Low-dose amitriptyline, a tricyclic antidepressant (TCA), was superior to placebo for irritable bowel syndrome (IBS) in the AmitripTyline at Low-dose ANd Titrated for Irritable bowel syndrome as Second-line treatment (ATLANTIS) trial. Objective To perform post hoc analyses of ATLANTIS for predictors of response to, and tolerability of, a TCA. Design ATLANTIS randomised 463 adults with IBS to amitriptyline (232) or placebo (231). We examined the effect of baseline demographic and disease-related patient characteristics on response to amitriptyline and the effect of amitriptyline on individual symptoms and side effects by subtype. Results There was a quantitative difference in amitriptyline effectiveness in those ≥50 years vs <50 on the IBS severity scoring system (IBS-SSS) (interaction p=0.048, mean difference in ≥50 years subgroup −46.5; 95% CI −74.2 to −18.8, p=0.0010), and subjective global assessment of relief (interaction p=0.068, OR in ≥50 years subgroup 2.59; 95% CI 1.47 to 4.55, p=0.0010), and those in the 70% most deprived areas of England compared with the 30% least deprived for a ≥30% improvement in abdominal pain (interaction p=0.021, OR in 70% most deprived subgroup 2.70; 95% CI 1.52 to 4.77, p=0.0007). Stronger treatment effects were seen in men, with higher Patient Health Questionnaire-12 scores, and with IBS with diarrhoea. Mean differences in individual IBS-SSS components favoured amitriptyline, and side effects were similar, across almost all IBS subtypes. Conclusion These exploratory analyses demonstrate there are unlikely to be deleterious effects of amitriptyline in any particular IBS subtype and could help identify patients in whom amitriptyline may be more effective. Trial registration number [ISRCTN48075063][1]. Data are available on reasonable request. All data requests should be submitted to the corresponding author, ACF, for consideration and would be subject to review by a subgroup of the trial team, which will include the data guarantor, AJF. Access to anonymised data may be granted following this review. All data-sharing activities would require a data-sharing agreement. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN48075063

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根据亚型预测低剂量阿米替林治疗肠易激综合征的反应以及疗效和耐受性：ATLANTIS试验的事后分析

背景：低剂量阿米替林是一种三环抗抑郁药（TCA），在低剂量阿米替林作为肠易激综合征二线治疗（ATLANTIS）试验中，治疗肠易激综合征（IBS）优于安慰剂。目的对ATLANTIS进行事后分析，以预测对TCA的反应和耐受性。ATLANTIS将463名成人IBS患者随机分为阿米替林组（232人）和安慰剂组（231人）。我们检查了基线人口统计学和疾病相关患者特征对阿米替林反应的影响，以及阿米替林按亚型对个体症状和副作用的影响。结果在IBS严重程度评分系统（IBS- sss）中，阿米替林有效性在≥50岁患者与<50岁患者之间存在定量差异(相互作用p=0.048，≥50岁亚组平均差异为- 46.5；95% CI为−74.2至−18.8,p=0.0010)，主观总体缓解评估(相互作用p=0.068， OR≥50岁亚组为2.59；95% CI 1.47 ~ 4.55, p=0.0010)， 70%最贫困地区的患者与30%最贫困地区的患者相比，腹痛改善≥30%(相互作用p=0.021, 70%最贫困亚组OR为2.70；95% CI 1.52 ~ 4.77, p=0.0007)。男性患者的治疗效果更强，患者健康问卷-12得分更高，肠易激综合征伴腹泻。在几乎所有IBS亚型中，个体IBS- sss成分的平均差异倾向于阿米替林，副作用相似。结论：这些探索性分析表明，阿米替林对任何特定的IBS亚型都不太可能产生有害影响，并有助于确定阿米替林可能更有效的患者。试验注册号[ISRCTN48075063][1]。如有合理要求，可提供资料。所有的数据请求都应提交给通讯作者ACF考虑，并由试验小组的一个小组进行审查，该小组将包括数据担保人AJF。在此审查之后，可能会授予访问匿名数据的权限。所有数据共享活动都需要数据共享协议。[1]: / external-ref吗?link_type = ISRCTN&access_num = ISRCTN48075063

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来源期刊

Gut 医学-胃肠肝病学

CiteScore

45.70

自引率

2.40%

发文量

284

审稿时长

1.5 months

期刊介绍： Gut is a renowned international journal specializing in gastroenterology and hepatology, known for its high-quality clinical research covering the alimentary tract, liver, biliary tree, and pancreas. It offers authoritative and current coverage across all aspects of gastroenterology and hepatology, featuring articles on emerging disease mechanisms and innovative diagnostic and therapeutic approaches authored by leading experts. As the flagship journal of BMJ's gastroenterology portfolio, Gut is accompanied by two companion journals: Frontline Gastroenterology, focusing on education and practice-oriented papers, and BMJ Open Gastroenterology for open access original research.