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

Author information

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: jpanes@clinic.cat.

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.

Abstract

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.