Higher vs Standard Adalimumab Induction Dosing Regimens and Two Maintenance Strategies: Randomized SERENE CD Trial Results

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 162; no. 7; pp. 1876 - 1890
• Main Authors: D’Haens, Geert R., Sandborn, William J., Loftus, Edward V., Hanauer, Stephen B., Schreiber, Stefan, Peyrin-Biroulet, Laurent, Panaccione, Remo, Panés, Julián, Baert, Filip, Colombel, Jean-Frederic, Ferrante, Marc, Louis, Edouard, Armuzzi, Alessandro, Zhou, Qian, Goteti, Venkata S., Mostafa, Nael M., Doan, Thao T., Petersson, Joel, Finney-Hayward, Tricia, Song, Alexandra P., Robinson, Anne M., Danese, Silvio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2022; Elsevier
• Subjects: Adalimumab; Adalimumab - administration & dosage; Adalimumab - adverse effects; Adult; Biologic Agent; C-Reactive Protein; C-Reactive Protein - metabolism; Crohn Disease; Crohn Disease - diagnosis; Crohn Disease - drug therapy; Crohn Disease - metabolism; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Inflammatory Bowel Disease; Life Sciences; Monoclonal Antibody; Remission Induction; TNF Inhibitor; Treatment Outcome; CD; AE; IBDQ; ITT; Biologic Agent; OLE; eow; PRO; Monoclonal Antibody; HIR; ew; TNF Inhibitor; AAA+; CDAI; SES-CD; Inflammatory Bowel Disease; TDM; hs-CRP; SIR; CA
• ISSN: 0016-5085; 1528-0012; 1528-0012
• DOI: 10.1053/j.gastro.2022.01.044

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. 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. 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. 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). The SERENE CD study results demonstrate no additional benefit of higher adalimumab induction dosing vs the approved standard induction dosing for treating patients with moderately to severely active Crohn’s disease.