Higher vs Standard Adalimumab Induction and Maintenance Dosing Regimens for Treatment of Ulcerative Colitis: SERENE UC Trial Results

doi:10.1053/j.gastro.2022.02.033

Gastroenterology

Volume 162, Issue 7, June 2022, Pages 1891-1910

https://doi.org/10.1053/j.gastro.2022.02.033 Get rights and content

Under a Creative Commons license

open access

Background & Aims

SERENE UC (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Ulcerative Colitis) evaluated the efficacy of higher adalimumab induction and maintenance dose regimens in patients with ulcerative colitis.

Methods

This phase 3, double-blind, randomized trial included induction and maintenance studies, with a main study (ex-Japan) and Japan substudy. Eligible patients (18–75 years, full Mayo score 6–12, centrally read endoscopy subscore 2–3) were randomized 3:2 to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3) or standard induction regimen (160 mg at week 0 and 80 mg at week 2); all received 40 mg at weeks 4 and 6. At week 8, all patients were rerandomized 2:2:1 (main study) to 40 mg every week (ew), 40 mg every other week (eow), or exploratory therapeutic drug monitoring; or 1:1 (Japan substudy) to 40 mg ew or 40 mg eow maintenance regimens.

Results

In the main study, 13.3% vs 10.9% of patients receiving the higher induction regimen vs standard induction regimen achieved clinical remission (full Mayo score ≤2 with no subscore >1) at week 8 (induction primary end point; P = .265); among week-8 responders, 39.5% vs 29.0% receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (maintenance primary end point; P = .069). In the integrated (main + Japan) population, 41.1% vs 30.1% of week-8 responders receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (nominal P = .045). Safety profiles were comparable between dosing regimens.

Conclusion

Although primary end points were not met, a >10% absolute difference in clinical remission was demonstrated with higher adalimumab maintenance dosing. Higher dosing regimens were generally well tolerated and consistent with the known safety profile of adalimumab in ulcerative colitis. ClinicalTrials.gov, Number: NCT002209456.

Keywords

Adalimumab

Monoclonal Antibody

Inflammatory Bowel Disease

Moderately to Severely Active Ulcerative Colitis

Clinical Trial Result

Abbreviations used in this paper

AAA

anti-adalimumab antibody

adverse event

AESI

adverse event of special interest

confidence interval

eow

every other week

every week

FMS

full Mayo score

HIR

higher induction regimen

hs-CRP

high-sensitivity C-reactive protein

IBDQ

Inflammatory Bowel Disease Questionnaire

IFX

infliximab

ITT

intent-to-treat

ITT-RP

intent-to-treat responder patient

RBS

rectal bleeding subscore

RHI

Robarts Histopathology Index

SFS

stool frequency subscore

SIR

standard induction regimen

TDM

therapeutic drug monitoring

TNF

tumor necrosis factor

ulcerative colitis

Cited by (0)

: Data Availability AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (eg, protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. This clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing agreement. Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

: Conflicts of interest These authors disclose the following: Julián Panés has received research grants from AbbVie and Pfizer; speaker’s fees from AbbVie, Ferring, Janssen, Merck, Pfizer, Shire, Takeda, and Theravance; and has been a consultant for AbbVie, Arena, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Genentech, GlaxoSmithKline, GoodGut, Janssen, Merck, Nestlé, Origo, Pandion, Pfizer, Progenity, Robarts Clinical Trials, Roche, Takeda, Theravance, and Wassermann. Jean-Frederic Colombel has received research grants from AbbVie, Janssen, and Takeda; speaker’s fees from AbbVie, Allergan, Amgen, Ferring, Shire, and Takeda; and consulting fees from AbbVie, Amgen, Arena, Boehringer Ingelheim, BMS, Celgene, Ferring, Galmed, Genentech, GlaxoSmithKline, Imedex, Immunic, Iterative Scopes, Janssen, Kaleido, LillyMerck, Microba, Novartis, PBM Capital, Pfizer, Sanofi, Takeda, TiGenix, and Vifor; he also holds stock options in Intestinal Biotech Development. Geert R. D’Haens has served as advisor for AbbVie, Ablynx, Active Biotech AB, Agomab Therapeutics, Alimentiv, Allergan, Alphabiomics, Amakem, Amgen, AM Pharma, Applied Molecular Therapeutics, Arena, AstraZeneca, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, DSM Pharma; Echo Pharmaceuticals, Eli Lilly, Engene, Exeliom Biosciences, Ferring, DrFALK Pharma, Galapagos, Genentech/Roche, Gilead, Glaxo Smith Kline, Gossamerbio, Pfizer, Immunic, Johnson and Johnson, Kintai Therapeutics, Lument, Lycera, Takeda, Medtronic, Mitsubishi Pharma, Merck Sharp Dome, Novonordisk, Otsuka, Photopill, ProciseDx, Prodigest, Prometheus laboratories/Nestle, Progenity, Protagonist, RedHill, Samsung Bioepis, Sandoz, Seres, Setpoint, Shire, Teva, Tillotts, Topivert, Versant, and Vifor. Stefan Schreiber has been a consultant for AbbVie, Amgen, Arena, Bristol Myers Squibb; Boehringer Ingelheim, Celltrion, Dr Falk Pharma, Ferring, Fresenius, Galapagos, Genentech, GlaxoSmithKline, Gilead, IMAB-Biopharma, Janssen, Lilly, Merck, Novartis/Sandoz, Pfizer, Protagonist, Takeda, and Theravance. Remo Panaccione has received consulting fees from AbbVie, Abbott, Alimentiv (formerly Robarts), Amgen, Arena, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Genentech, Gilead Sciences, Glaxo-Smith Kline, Janssen, Merck, Mylan, Oppilan Pandion, Pharma, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Satisfai Health, Sandoz, Schering-Plough, Shire, Sublimity Therapeutics, Theravance, UCB, and Takeda; speaker fees from AbbVie, Arena, Celgene, Eli Lilly, Ferring, Gilead Sciences, Janssen, Merck, Pfizer, Roche, Sandoz, Shire, and Takeda; research/educational support from AbbVie, Ferring, Janssen, Pfizer, and Takeda; and has served on an advisory board for AbbVie, Amgen, Arena, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Genentech, Gilead Sciences, Glaxo-Smith Kline, Janssen, Merck, Mylan, Oppilan Pharma, Pandion Pharma, Pfizer, Sandoz, Shire, Sublimity Therapeutics, Theravance, and Takeda. Laurent Peyrin-Biroulet has received personal fees from AbbVie, Allergan, Amgen, Arena, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Merck, Mylan, Norgine, OSE Immunotherapeutics, Pandion Therapeutics, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Theravance, Thermofisher, Tillotts, Viatris, and Vifor; and grants from AbbVie, Fresenius Kabi, Merck, and Takeda. He also holds CTMA stock options. Edward V. Loftus Jr has been a consultant for AbbVie, Allergan, Amgen, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Calibr, Celgene, Celltrion, Genentech, Gilead, Iterative Scopes, Janssen, Lilly, Ono Pharma, Pfizer, Sun Pharma, Takeda, and UCB; and received research grants from AbbVie, Amgen, Bristol Myers Squibb, Genentech, Gilead, Janssen, Pfizer, Receptos (Celgene), Robarts Clinical Trials, Takeda, Theravance, and UCB. Silvio Danese has received research grants from AbbVie, Amgen, Celgene, Genentech, Gilead, Janssen, Pfizer, Receptos (Celgene), Robarts Clinical Trials, Seres Therapeutics, Takeda, and UCB; and been a consultant for AbbVie, Allergan, Amgen, Bristol Myers Squibb, Celgene, Celltrion, Janssen, Lilly, Pfizer, Takeda, and UCB. Satoshi Tanida has received research grants from AbbVie and EA Pharma. Edouard Louis has received research grants from Takeda, Pfizer, and Janssen; educational grants from AbbVie, Takeda, and Janssen; speaker fees from AbbVie, Ferring, MSD, Falk, Takeda, Janssen, Pfizer, and Celgene; participated in advisory boards for AbbVie, Ferring, MSD, Takeda, Celgene, Janssen, Gilead-Galapagos, Arena, Pfizer, and Eli Lilly; and has been a consultant for AbbVie. Alessandro Armuzzi has been a consultant or advisory board member for AbbVie, Allergan, Amgen, Arena, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Ferring, Galapagos, Gilead, Janssen, Lilly, Merck, Mylan, Pfizer, Roche, Samsung Bioepis, Sandoz, Sofar SpA, and Takeda; has received speaker’s fees from AbbVie, Amgen, Arena, Biogen, Bristol Myers Squibb, Ferring, Galapagos, Gilead, Janssen, Medtronic, Merck, Mitsubishi Tanabe Pharma, Nikkiso, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, and TiGenix; and received research grants from Merck, Pfizer, and Takeda. Marc Ferrante has been a consultant for AbbVie, Boehringer Ingelheim, Celltrion, Janssen, Lilly, Medtronic, Merck, Pfizer, Sandoz, Takeda, and Thermo Fisher; has received research grants from AbbVie, Amgen, Biogen, Janssen, Pfizer, and Takeda; and received speaker’s fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen, Lamepro BV, Merck, Mylan, Pfizer, Sandoz, Takeda, and Truvion Healthcare. Harald Vogelsang has received consulting and/or speaker’s fees from AbbVie, Amgen, Astro Pharma, Bristol Myers Squibb, Dr Falk Pharma, Ferring, Gilead, Janssen, Merck, MSD, Pfizer, and Takeda. Toshifumi Hibi is an editor of Intestinal Research and has received grants, personal fees, and/or other funds from AbbVie, Aspen Pharmacare, Celltrion, EA Pharma, Ferring, Gilead, Janssen, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Lilly, Mitsubishi Tanabe Pharma, Miyarisan Pharmaceutical, Mochida Pharmaceutical, Nichi-Iko, Nippon Kayaku, Otsuka, Pfizer, Takeda, and Zeria Pharmaceutical. Mamoru Watanabe has received grants, personal fees, and/or other funds from AbbVie, Alfresa Pharma, Asahi Kasei Medical, Astellas, Ayumi Pharmaceutical, Celgene, Celltrion, Chugai, Daiichi Sankyo, EA Pharma, Eisai, Fujirebio, Gilead, Janssen, JIMRO, Kaken Pharmaceutical, Kissei Pharmaceutical, Kyorin Pharmaceutical, Kyowa Kirin, Lilly, Merck, Mitsubishi Tanabe Pharma, Miyarisan Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Taiho Pharmaceutical, Takeda, Toray Industries, and Zeria Pharmaceutical. Jessica Lefebvre, Thao T. Doan, Nael M. Mostafa, Wangang Xie, Bidan Huang, Joel Petersson, Tricia Finney-Hayward, Jasmina Kalabic, Kimitoshi Ikeda, Yuri Sanchez Gonzalez, and Anne M. Robinson are full-time employees of AbbVie, and may own AbbVie stock or options. William J. Sandborn has received research grants from AbbVie, Abivax, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Genentech, Gilead Sciences, Glaxo Smith Kline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Takeda, and Theravance Biopharma; consulting fees from AbbVie, Abivax, Alfasigma, Alimentiv (previously Robarts Clinical Trials, owned by Alimentiv Health Trust), Allakos, Amgen, Arena, AstraZeneca, Atlantic Pharmaceuticals, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Clostrabio, Forbion, Galapagos, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Iota Biosciences, Janssen, Lilly, Morphic Therapeutics, Novartis, Oppilan Pharma (now Venytx Biosciences), Pfizer, Pharm Olam, Polpharm, Progenity, Prometheus Biosciences, Protagonists Therapeutics, PTM Therapeutics, Seres Therapeutics, Shoreline Biosciences, Sublimity Therapeutics, Surrozen, Takeda, Theravance Biopharma, Vendata Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivreon Gastrosciences, Xencor, and Zealand Pharmaceuticals; stock or stock options from Allakos, BeiGene, Gossamer Bio, Oppilan Pharma (now Ventyx Biosciences), Prometheus Biosciences, Prometheus Laboratories Protagonists Therapeutics, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivreon Gastrosciences; and employee at Shoreline Biosciences. Spouse: Iveric Bio - consultant, stock options; Progenity - stock; Oppilan Pharma (now Ventyx Biosciences) - stock; Prometheus Biosciences - employee, stock, stock options; Prometheus Laboratories – stock, stock options, consultant; Ventyx Biosciences – stock, stock options; Vimalan Biosciences – stock, stock options. The remaining author discloses no conflicts.

: Funding AbbVie funded the research for this study and provided writing support for this manuscript. AbbVie Inc participated in the study design; study research; collection, analysis, and interpretation of data; and writing, reviewing, and approving of this manuscript. All authors had access to the data, and participated in the development, review, and approval, and in the decision to submit this manuscript for publication. Medical writing assistance was funded by AbbVie.

^∗: Alessandro Armuzzi is now at Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Research Hospital, Rozzano, Milan, Italy.