Panés Julián, Colombel Jean-Frederic, D'Haens Geert R, Schreiber Stefan, Panaccione Remo, Peyrin-Biroulet Laurent, Loftus Edward V, Danese Silvio, Tanida Satoshi, Okuyama Yusuke, Louis Edouard, Armuzzi Alessandro, Ferrante Marc, Vogelsang Harald, Hibi Toshifumi, Watanabe Mamoru, Lefebvre Jessica, Finney-Hayward Tricia, Sanchez Gonzalez Yuri, Doan Thao T, Mostafa Nael M, Ikeda Kimitoshi, Xie Wangang, Huang Bidan, Petersson Joel, Kalabic Jasmina, Robinson Anne M, Sandborn William J
Hospital Clinic de Barcelona, August Pi i Sunyer Biomedical Research Institute, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Barcelona, Spain.
Icahn School of Medicine at Mt Sinai, New York, New York.
Gastroenterology. 2022 Jun;162(7):1891-1910. doi: 10.1053/j.gastro.2022.02.033. Epub 2022 Feb 25.
BACKGROUND & AIMS: SERENE UC (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Ulcerative Colitis) evaluated the efficacy of higher adalimumab induction and maintenance dose regimens in patients with ulcerative colitis.
This phase 3, double-blind, randomized trial included induction and maintenance studies, with a main study (ex-Japan) and Japan substudy. Eligible patients (18-75 years, full Mayo score 6-12, centrally read endoscopy subscore 2-3) were randomized 3:2 to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3) or standard induction regimen (160 mg at week 0 and 80 mg at week 2); all received 40 mg at weeks 4 and 6. At week 8, all patients were rerandomized 2:2:1 (main study) to 40 mg every week (ew), 40 mg every other week (eow), or exploratory therapeutic drug monitoring; or 1:1 (Japan substudy) to 40 mg ew or 40 mg eow maintenance regimens.
In the main study, 13.3% vs 10.9% of patients receiving the higher induction regimen vs standard induction regimen achieved clinical remission (full Mayo score ≤2 with no subscore >1) at week 8 (induction primary end point; P = .265); among week-8 responders, 39.5% vs 29.0% receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (maintenance primary end point; P = .069). In the integrated (main + Japan) population, 41.1% vs 30.1% of week-8 responders receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (nominal P = .045). Safety profiles were comparable between dosing regimens.
Although primary end points were not met, a >10% absolute difference in clinical remission was demonstrated with higher adalimumab maintenance dosing. Higher dosing regimens were generally well tolerated and consistent with the known safety profile of adalimumab in ulcerative colitis.
gov, Number: NCT002209456.
SERENE UC（中重度溃疡性结肠炎患者使用阿达木单抗诱导和维持给药新方法的研究）评估了较高剂量阿达木单抗诱导和维持给药方案对溃疡性结肠炎患者的疗效。
这项3期双盲随机试验包括诱导和维持研究，有一项主要研究（日本境外）和日本子研究。符合条件的患者（18 - 75岁，梅奥总评分6 - 12分，中心阅片内镜亚评分2 - 3分）按3:2随机分为较高诱导方案组（第0、1、2和3周给予阿达木单抗160mg）或标准诱导方案组（第0周给予160mg，第2周给予80mg）；所有患者在第4周和第6周均接受40mg。在第8周，所有患者再次随机分组，主要研究中按2:2:1分为每周40mg（ew）、每2周40mg（eow）或探索性治疗药物监测组；在日本子研究中按1:1分为40mg ew或40mg eow维持方案组。
在主要研究中，第8周时接受较高诱导方案组与标准诱导方案组的患者实现临床缓解（梅奥总评分≤2分且无亚评分>）的比例分别为13.3%和10.9%（诱导主要终点；P = 0.265）；在第8周的缓解者中，接受40mg ew与40mg eow的患者在第52周实现临床缓解（维持主要终点；P = 0.069）的比例分别为39.5%和29.0%。在综合（主要研究 + 日本）人群中，接受40mg ew与40mg eow的第8周缓解者在第52周实现临床缓解的比例分别为41.1%和30.1%（名义P = 0.045）。各给药方案的安全性相当。
虽然未达到主要终点，但较高剂量阿达木单抗维持给药在临床缓解方面显示出>10%的绝对差异。较高剂量方案总体耐受性良好，与阿达木单抗在溃疡性结肠炎中的已知安全性相符。
gov，编号：NCT002209456。
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