- Fecal Incontinence
|Higher vs Standard Adalimumab Induction Dosing Regimens and Two Maintenance Strategies: Randomized SERENE CD Trial Results
Gastroenterology. 2022 Jun;162(7):1876-1890.doi: 10.1053/j.gastro.2022.01.044. Epub 2022 Feb 3.
Geert R D'Haens 1, William J Sandborn 2, Edward V Loftus Jr 3, Stephen B Hanauer 4, Stefan Schreiber 5, Laurent Peyrin-Biroulet 6, Remo Panaccione 7, Julián Panés 8, Filip Baert 9, Jean-Frederic Colombel 10, Marc Ferrante 11, Edouard Louis 12, Alessandro Armuzzi 13, Qian Zhou 14, Venkata S Goteti 14, Nael M Mostafa 14, Thao T Doan 14, Joel Petersson 14, Tricia Finney-Hayward 15, Alexandra P Song 14, Anne M Robinson 14, Silvio Danese 16
1Amsterdam Gastroenterology Endocrinology Metabolism and Gastroenterology and Hepatology Departments, Amsterdam University Medical Centers, Amsterdam, the Netherlands. Electronic address: email@example.com.
2Gastroenterology Department, University of California San Diego, La Jolla, California.
3Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
4Department of Medicine (Gastroenterology and Hepatology), Northwestern University, Chicago, Illinois.
5Department of Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.
6Department of Gastroenterology, Centre Hospitalier Règional Universitaire de Nancy, Nutrition-Genetics and Exposure to Environmental Risks, Institut National de la Santè et de la Recherche Mèdicale, University of Lorraine, Nancy, France.
7Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
8Department of Gastroenterology, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Barcelona, Spain.
9Department of Gastroenterology, AZ Delta, Roeselare-Menen, Belgium.
10Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
11Department of Gastroenterology and Hepatology, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
12Department of Gastroenterology, University Hospital Centre Hospitalier Universitaire de Liège, Liège, Belgium.
13Inflammatory Bowel Diseases Unit, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
14AbbVie Inc, North Chicago, Illinois.
15AbbVie Ltd, Maidenhead, Berkshire, England, United Kingdom.
16Gastroenterology and Endoscopy, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy.
Background & aims: Dose-optimization strategies for biologic therapies in Crohn's disease (CD) are not well established. The SERENE CD (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Crohn's Disease) trial evaluated higher vs standard adalimumab induction dosing and clinically adjusted (CA) vs therapeutic drug monitoring (TDM) maintenance strategies in patients with moderately to severely active CD.
Methods: In this phase 3, randomized, double-blind, multicenter trial, eligible adults (Crohn's Disease Activity Index score of 220-450, endoscopic evidence of mucosal inflammation, and previous failure of standard therapies) were randomized to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3; n = 308) or standard induction regimen (adalimumab 160 mg at week 0 and 80 mg at week 2; n = 206) followed by 40 mg every other week from week 4 onward. Co-primary end points included clinical remission at week 4 and endoscopic response at week 12. At week 12, patients were re-randomized to maintenance therapy optimized by Crohn's Disease Activity Index and C-reactive protein (CA; n = 92) or serum adalimumab concentrations and/or clinical criteria (TDM; n = 92); exploratory end points were evaluated at week 56.
Results: Similar proportions of patients receiving higher induction regimen and standard induction regimen achieved clinical remission at week 4 (44% in both; P = .939) and endoscopic response at week 12 (43% vs 39%, respectively, P = .462). Week 56 efficacy was similar between CA and TDM. Safety profiles were comparable between dosing regimens.
Conclusions: Higher induction regimen was not superior to standard induction regimen, and CA and TDM maintenance strategies were similarly efficacious. Adalimumab therapy was well tolerated, and no new safety concerns were identified. (ClinicalTrials.gov, Number: NCT02065570).