Long-term Efficacy and Tolerability of RPC4046 in an Open-Label Extension Trial of Patients With Eosinophilic Esophagitis,Clinical Gastroenterology and Hepatology

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Long-term Efficacy and Tolerability of RPC4046 in an Open-Label Extension Trial of Patients With Eosinophilic Esophagitis
Clinical Gastroenterology and Hepatology ( IF 12.6 ) Pub Date : 2020-03-21 , DOI: 10.1016/j.cgh.2020.03.036
Evan S Dellon ₁ , Margaret H Collins ₂ , Marc E Rothenberg ₃ , Yehudith Assouline-Dayan ₄ , Larry Evans ₅ , Sandeep Gupta ₆ , Alain Schoepfer ₇ , Alex Straumann ₈ , Ekaterina Safroneeva ₉ , Cristian Rodriguez ₁₀ , Neil Minton ₁₁ , Steven Y Hua ₁₂ , Ikuo Hirano ₁₃

Affiliation

Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Department of Gastroenterology, Carver College of Medicine, University of Iowa, Iowa City, Iowa.
Department of Gastroenterology, Grand Teton Research Group, Idaho Falls, Idaho.
Department of Pediatrics, University of Illinois College of Medicine, Children's Hospital of Illinois, Peoria, Illinois.
Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Division of Gastroenterology and Hepatology, Swiss EoE Clinic, Olten, Switzerland.
Institute of Social and Preventative Medicine, University of Bern, Bern, Switzerland.
Inflammation & Fibrosis, Summit, New Jersey.
Drug Safety, Summit, New Jersey.
Department of Biostatistics, Summit, New Jersey.
Division of Medicine, Gastroenterology, Feinberg School of Medicine, Chicago, Illinois.

Background & Aims

The short-term efficacy of RPC4046, a monoclonal antibody against interleukin-13, has been shown in patients with eosinophilic esophagitis (EoE). We investigated the long-term efficacy and safety of RPC4046 in an open-label, long-term extension (LTE) study in adults with EoE.

Methods

We analyzed data from 66 patients who completed the 16-week, double-blind, induction portion of a phase 2 study of RPC4046 (180 mg or 360 mg/wk) vs placebo and then completed a 52-week LTE, receiving open-label RPC4046 360 mg/wk. The study was conducted at 28 centers in 3 countries; patients were enrolled between September 2014 and January 2017. Outcomes were stratified by double-blind dose group and included esophageal eosinophil counts, EoE endoscopic reference score, EoE histologic scoring system score, symptom-based EoE activity index score, and safety.

Results

By week 12 of the LTE, esophageal eosinophil mean and peak counts, total EoE endoscopic reference scores, and EoE histologic scoring system grade and stage scores did not differ considerably between patients who originally received placebo vs RPC4046. Most patients maintained responses through week 52. Symptom remission (symptom-based EoE activity index score, ≤20) increased from 14% at LTE entry to 67% at LTE week 52 in placebo‒RPC4046 patients and from 30% to 54% in RPC4046‒RPC4046 (either dose) patients. Of the 28 patients who did not have a histologic response to RPC4046 during the double-blind induction phase, 10 patients (36%) achieved response during the LTE. The most common adverse events were upper respiratory tract infection (21%) and nasopharyngitis (14%).

Conclusions

One year of treatment with RPC4046 is generally well tolerated and results in continued improvement and/or maintenance of endoscopic, histologic, and clinical measures of EoE disease activity relative to baseline. Trial registration: NCT02098473.

中文翻译：

RPC4046在嗜酸性食管炎患者开放标签扩展试验中的长期疗效和耐受性

背景与目标

RPC4046 是一种针对白细胞介素 13 的单克隆抗体，其短期疗效已在嗜酸性粒细胞性食管炎 (EoE) 患者中得到证实。我们在 EoE 成人的一项开放标签、长期扩展 (LTE) 研究中调查了 RPC4046 的长期疗效和安全性。

方法

我们分析了 66 名患者的数据，他们完成了 RPC4046（180 毫克或 360 毫克/周）与安慰剂的 2 期研究的 16 周、双盲、诱导部分，然后完成了 52 周的 LTE，接受了开放标签RPC4046 360 毫克/周。该研究在 3 个国家的 28 个中心进行；患者在 2014 年 9 月至 2017 年 1 月期间入组。结果按双盲剂量组分层，包括食管嗜酸性粒细胞计数、EoE 内镜参考评分、EoE 组织学评分系统评分、基于症状的 EoE 活动指数评分和安全性。

结果

到 LTE 的第 12 周，最初接受安慰剂与 RPC4046 的患者之间的食管嗜酸性粒细胞平均和峰值计数、总 EoE 内镜参考评分以及 EoE 组织学评分系统分级和分期评分没有显着差异。大多数患者在第 52 周内保持反应。症状缓解（基于症状的 EoE 活动指数评分，≤20）在安慰剂-RPC4046 患者中从 LTE 进入时的 14% 增加到 LTE 第 52 周时的 67%，在 RPC4046 中从 30% 增加到 54% ‒RPC4046（任一剂量）患者。在双盲诱导阶段对 RPC4046 没有组织学反应的 28 名患者中，10 名患者 (36%) 在 LTE 期间获得了反应。最常见的不良事件是上呼吸道感染（21%）和鼻咽炎（14%）。