[en] 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).
Disciplines :
Gastroenterology & hepatology
Author, co-author :
D'Haens, Geert R; Amsterdam Gastroenterology Endocrinology Metabolism and Gastroenterology and
Sandborn, William J; Gastroenterology Department, University of California San Diego, La Jolla,
Loftus, Edward V Jr; Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
Hanauer, Stephen B; Department of Medicine (Gastroenterology and Hepatology), Northwestern
Schreiber, Stefan; Department of Internal Medicine, University Hospital Schleswig-Holstein, Kiel,
Peyrin-Biroulet, Laurent; Department of Gastroenterology, Centre Hospitalier Règional Universitaire de
Panaccione, Remo; Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Panés, Julián; Department of Gastroenterology, Hospital Clinic Barcelona, August Pi i Sunyer
Baert, Filip; Department of Gastroenterology, AZ Delta, Roeselare-Menen, Belgium.
Colombel, Jean-Frederic; Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York,
Ferrante, Marc; Department of Gastroenterology and Hepatology, University Hospitals Leuven,
Louis, Edouard ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gastroentérologie, hépatologie, onco. digestive ; Department of Gastroenterology, University Hospital Centre Hospitalier
Armuzzi, Alessandro; Inflammatory Bowel Diseases Unit, Fondazione Policlinico Universitario A. Gemelli
Zhou, Qian; AbbVie Inc, North Chicago, Illinois.
Goteti, Venkata S; AbbVie Inc, North Chicago, Illinois.
Mostafa, Nael M; AbbVie Inc, North Chicago, Illinois.
Doan, Thao T; AbbVie Inc, North Chicago, Illinois.
Petersson, Joel; AbbVie Inc, North Chicago, Illinois.
Finney-Hayward, Tricia; AbbVie Ltd, Maidenhead, Berkshire, England, United Kingdom.
Song, Alexandra P; AbbVie Inc, North Chicago, Illinois.
Robinson, Anne M; AbbVie Inc, North Chicago, Illinois.
Danese, Silvio; Gastroenterology and Endoscopy, Istituto di Ricovero e Cura a Carattere
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