- Fecal Incontinence
|Higher vs Standard Adalimumab Induction and Maintenance Dosing Regimens for Treatment of Ulcerative Colitis: SERENE UC Trial Results
Gastroenterology. 2022 Feb 25;S0016-5085(22)00199-8. doi: 10.1053/j.gastro.2022.02.033.Online ahead of print.
Julián Panés 1, Jean-Frederic Colombel 2, Geert R D'Haens 3, Stefan Schreiber 4, Remo Panaccione 5, Laurent Peyrin-Biroulet 6, Edward V Loftus Jr 7, Silvio Danese 8, Satoshi Tanida 9, Yusuke Okuyama 10, Edouard Louis 11, Alessandro Armuzzi 12, Marc Ferrante 13, Harald Vogelsang 14, Toshifumi Hibi 15, Mamoru Watanabe 16, Jessica Lefebvre 17, Tricia Finney-Hayward 18, Yuri Sanchez Gonzalez 17, Thao T Doan 17, Nael M Mostafa 17, Kimitoshi Ikeda 19, Wangang Xie 17, Bidan Huang 17, Joel Petersson 17, Jasmina Kalabic 20, Anne M Robinson 17, William J Sandborn 21
1Hospital Clinic de Barcelona, The August Pi i Sunyer Biomedical Research Institute, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Barcelona, Spain. Electronic address: firstname.lastname@example.org.
2Icahn School of Medicine at Mt Sinai, New York, New York.
3Amsterdam University Medical Centers, Amsterdam, the Netherlands.
4University Hospital Schleswig-Holstein, Department Internal Medicine I, Kiel University, Kiel, Germany.
5University of Calgary, Calgary, Alberta, Canada.
6Department of Gastroenterology, Centre Hospitalier Régional Universitaire de Nancy, Nutrition-Genetics and Environmental Risk Exposure, Institut National de la Santé et de la Recherche Médicale, University of Lorraine, Nancy, France.
7Mayo Clinic, Rochester, Minnesota.
8Gastroenterology and Endoscopy, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy.
9Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
10Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
11University Hospital Centre Hospitalier Universitaire of Liège, Liège, Belgium.
12Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Research Hospital, Rozzano, Milan, Italy.
13University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
14Medical University of Vienna, Vienna, Austria.
15Center for Advanced Inflammatory Bowel Disease Research and Treatment, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan.
16Advanced Research Institute and Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
17AbbVie Inc, North Chicago, Illinois.
18AbbVie Ltd, Maidenhead, Berkshire, England, United Kingdom.
19AbbVie GK, Minato-ku, Tokyo, Japan.
20AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany.
21University of California San Diego, La Jolla, California.
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.
Methods: 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.
Results: 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.
Conclusion: 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.
Clinicaltrials: gov, Number: NCT002209456.