Higher vs Standard Adalimumab Induction and Maintenance Dosing Regimens for Treatment of Ulcerative Colitis: SERENE UC Trial Results.

Julián Panés, Jasmina Kalabic, Wangang Xie, Kimitoshi Ikeda, Yuri Sanchez Gonzalez, Jessica Lefebvre, Mamoru Watanabe, Toshifumi Hibi, Harald Vogelsang, Yusuke Okuyama, Satoshi Tanida, Stefan Schreiber, Geert R D'Haens, Jean-Frederic Colombel, Remo Panaccione, Bidan Huang, Silvio Danese, Anne M Robinson, Tricia Finney-Hayward, Joel Petersson, Thao T Doan, Nael M Mostafa, Alessandro Armuzzi, Edouard Louis, Marc Ferrante, Laurent Peyrin-Biroulet, Edward V Loftus, William J Sandborn

Journal: Gastroenterology 2022;162(7):1891-1910

PMID: 35227777

Free Full Text on Elsevier Science View on PubMed

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.

Address: Hospital Clinic de Barcelona, August Pi i Sunyer Biomedical Research Institute, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Barcelona, Spain. Electronic address: [email protected].; Icahn School of Medicine at Mt Sinai, New York, New York.; Amsterdam Gastroenterology Endocrinology Metabolism and Gastroenterology and Hepatology Departments, Amsterdam University Medical Centers, Amsterdam, the Netherlands.; Department of Internal Medicine, University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany.; Department of Medicine, University of Calgary, Calgary, Alberta, Canada.; Department of Gastroenterology, Centre Hospitalier Régional Universitaire de Nancy, Nutrition-Genetics and Exposure to Environmental Risks, Institut National de la Santé et de la Recherche Médicale, University of Lorraine, Nancy, France.; Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.; Gastroenterology and Endoscopy, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy.; Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.; Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.; Department of Gastroenterology, University Hospital Centre Hospitalier Universitaire de Liège, Liège, Belgium.; Inflammatory Bowel Diseases Unit, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.; Department of Gastroenterology and Hepatology, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.; Medical University of Vienna, Vienna, Austria.; Center for Advanced Inflammatory Bowel Disease Research and Treatment, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan.; Advanced Research Institute and Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.; AbbVie Inc, North Chicago, Illinois.; AbbVie Ltd, Maidenhead, Berkshire, England, United Kingdom.; AbbVie GK, Minato-ku, Tokyo, Japan.; AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany.; Gastroenterology Department, University of California San Diego, La Jolla, California.

DOI: 10.1053/j.gastro.2022.02.033