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

Author information

¹Amsterdam Gastroenterology Endocrinology Metabolism and Gastroenterology and Hepatology Departments, Amsterdam University Medical Centers, Amsterdam, the Netherlands. Electronic address: g.dhaens@amsterdamumc.nl.

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.

Abstract

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).