TY - JOUR
T1 - Higher vs Standard Adalimumab Induction Dosing Regimens and Two Maintenance Strategies
T2 - Randomized SERENE CD Trial Results
AU - D'Haens, Geert R.
AU - Sandborn, William J.
AU - Loftus, Edward V.
AU - Hanauer, Stephen B.
AU - Schreiber, Stefan
AU - Peyrin-Biroulet, Laurent
AU - Panaccione, Remo
AU - Panés, Julián
AU - Baert, Filip
AU - Colombel, Jean Frederic
AU - Ferrante, Marc
AU - Louis, Edouard
AU - Armuzzi, Alessandro
AU - Zhou, Qian
AU - Goteti, Venkata S.
AU - Mostafa, Nael M.
AU - Doan, Thao T.
AU - Petersson, Joel
AU - Finney-Hayward, Tricia
AU - Song, Alexandra P.
AU - Robinson, Anne M.
AU - Danese, Silvio
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/6
Y1 - 2022/6
N2 - 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).
AB - 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).
KW - Biologic Agent
KW - Inflammatory Bowel Disease
KW - Monoclonal Antibody
KW - TNF Inhibitor
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U2 - 10.1053/j.gastro.2022.01.044
DO - 10.1053/j.gastro.2022.01.044
M3 - Article
C2 - 35122766
AN - SCOPUS:85127578506
SN - 0016-5085
VL - 162
SP - 1876
EP - 1890
JO - Gastroenterology
JF - Gastroenterology
IS - 7
ER -