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

Julián Panés; Jean Frederic Colombel; Geert R. D'Haens; Stefan Schreiber; Remo Panaccione; Laurent Peyrin-Biroulet; Edward V. Loftus; Silvio Danese; Satoshi Tanida; Yusuke Okuyama; Edouard Louis; Alessandro Armuzzi; Marc Ferrante; Harald Vogelsang; Toshifumi Hibi; Mamoru Watanabe; Jessica Lefebvre; Tricia Finney-Hayward; Yuri Sanchez Gonzalez; Thao T. Doan; Nael M. Mostafa; Kimitoshi Ikeda; Wangang Xie; Bidan Huang; Joel Petersson; Jasmina Kalabic; Anne M. Robinson; William J. Sandborn

doi:10.1053/j.gastro.2022.02.033

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

Julián Panés, Jean Frederic Colombel, Geert R. D'Haens, Stefan Schreiber, Remo Panaccione, Laurent Peyrin-Biroulet, Edward V. Loftus, Silvio Danese, Satoshi Tanida, Yusuke Okuyama, Edouard Louis, Alessandro Armuzzi, Marc Ferrante, Harald Vogelsang, Toshifumi Hibi, Mamoru Watanabe, Jessica Lefebvre, Tricia Finney-Hayward, Yuri Sanchez Gonzalez, Thao T. DoanNael M. Mostafa, Kimitoshi Ikeda, Wangang Xie, Bidan Huang, Joel Petersson, Jasmina Kalabic, Anne M. Robinson, William J. Sandborn

Gastroenterology and Hepatology

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Pages (from-to)	1891-1910
Number of pages	20
Journal	Gastroenterology
Volume	162
Issue number	7
DOIs	https://doi.org/10.1053/j.gastro.2022.02.033
State	Published - Jun 2022

Keywords

Adalimumab
Clinical Trial Result
Inflammatory Bowel Disease
Moderately to Severely Active Ulcerative Colitis
Monoclonal Antibody

ASJC Scopus subject areas

Hepatology
Gastroenterology

Access to Document

10.1053/j.gastro.2022.02.033

Cite this

Panés, J., Colombel, J. F., D'Haens, G. R., Schreiber, S., Panaccione, R., Peyrin-Biroulet, L., Loftus, E. V., Danese, S., Tanida, S., Okuyama, Y., Louis, E., Armuzzi, A., Ferrante, M., Vogelsang, H., Hibi, T., Watanabe, M., Lefebvre, J., Finney-Hayward, T., Sanchez Gonzalez, Y., ... Sandborn, W. J. (2022). Higher vs Standard Adalimumab Induction and Maintenance Dosing Regimens for Treatment of Ulcerative Colitis: SERENE UC Trial Results. Gastroenterology, 162(7), 1891-1910. https://doi.org/10.1053/j.gastro.2022.02.033

Panés, J, Colombel, JF, D'Haens, GR, Schreiber, S, Panaccione, R, Peyrin-Biroulet, L, Loftus, EV, Danese, S, Tanida, S, Okuyama, Y, Louis, E, Armuzzi, A, Ferrante, M, Vogelsang, H, Hibi, T, Watanabe, M, Lefebvre, J, Finney-Hayward, T, Sanchez Gonzalez, Y, Doan, TT, Mostafa, NM, Ikeda, K, Xie, W, Huang, B, Petersson, J, Kalabic, J, Robinson, AM & Sandborn, WJ 2022, 'Higher vs Standard Adalimumab Induction and Maintenance Dosing Regimens for Treatment of Ulcerative Colitis: SERENE UC Trial Results', Gastroenterology, vol. 162, no. 7, pp. 1891-1910. https://doi.org/10.1053/j.gastro.2022.02.033

@article{415bb95de16b431f945b89d2c826bc63,

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

abstract = "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, Clinical Trial Result, Inflammatory Bowel Disease, Moderately to Severely Active Ulcerative Colitis, Monoclonal Antibody",

author = "Juli{\'a}n Pan{\'e}s and Colombel, {Jean Frederic} and D'Haens, {Geert R.} and Stefan Schreiber and Remo Panaccione and Laurent Peyrin-Biroulet and Loftus, {Edward V.} and Silvio Danese and Satoshi Tanida and Yusuke Okuyama and Edouard Louis and Alessandro Armuzzi and Marc Ferrante and Harald Vogelsang and Toshifumi Hibi and Mamoru Watanabe and Jessica Lefebvre and Tricia Finney-Hayward and {Sanchez Gonzalez}, Yuri and Doan, {Thao T.} and Mostafa, {Nael M.} and Kimitoshi Ikeda and Wangang Xie and Bidan Huang and Joel Petersson and Jasmina Kalabic and Robinson, {Anne M.} and Sandborn, {William J.}",

note = "Funding Information: AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. The authors thank Lynn Randall (AbbVie) for contributing to data interpretation and James W. Butler, a former AbbVie employee, for contributing to statistical analysis and data interpretation. William Sandborn was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases–funded San Diego Digestive Diseases Research Center (P30 DK120515). Medical writing assistance, funded by AbbVie, was provided by Caroline W. Cazares, PhD, of JB Ashtin. Funding Information: AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. The authors thank Lynn Randall (AbbVie) for contributing to data interpretation and James W. Butler, a former AbbVie employee, for contributing to statistical analysis and data interpretation. William Sandborn was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases–funded San Diego Digestive Diseases Research Center (P30 DK120515). Medical writing assistance, funded by AbbVie, was provided by Caroline W. Cazares, PhD, of JB Ashtin. Juli{\'a}n Pan{\'e}s, MD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Jean-Frederic Colombel, MD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Geert R. D'Haens, MD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Stefan Schreiber, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Remo Panaccione, MD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Laurent Peyrin-Biroulet, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Edward V. Loftus Jr, MD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Silvio Danese, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Satoshi Tanida, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Yusuke Okuyama, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Edouard Louis, MD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Alessandro Armuzzi, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Marc Ferrante, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Harald Vogelsang, MD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Toshifumi Hibi, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Mamoru Watanabe, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Jessica Lefebvre, MD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Tricia Finney-Hayward, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Yuri Sanchez Gonzalez, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Thao T. Doan, MD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Nael M. Mostafa, PhD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Kimitoshi Ikeda, PhD (Data curation: Equal; Formal analysis: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Wangang Xie, PhD (Data curation: Equal; Formal analysis: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Bidan Huang, PhD (Conceptualization: Equal; Data curation: Equal; Formal analysis: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Joel Petersson, MD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Jasmina Kalabic, MD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Anne M. Robinson, PharmD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). William J. Sandborn, MD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal) Conflicts of interest These authors disclose the following: Juli{\'a}n Pan{\'e}s 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, Nestl{\'e}, 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. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = jun,

doi = "10.1053/j.gastro.2022.02.033",

language = "English (US)",

volume = "162",

pages = "1891--1910",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders Ltd",

number = "7",

}

TY - JOUR

T1 - Higher vs Standard Adalimumab Induction and Maintenance Dosing Regimens for Treatment of Ulcerative Colitis

T2 - SERENE UC Trial Results

AU - Panés, Julián

AU - Colombel, Jean Frederic

AU - D'Haens, Geert R.

AU - Schreiber, Stefan

AU - Panaccione, Remo

AU - Peyrin-Biroulet, Laurent

AU - Loftus, Edward V.

AU - Danese, Silvio

AU - Tanida, Satoshi

AU - Okuyama, Yusuke

AU - Louis, Edouard

AU - Armuzzi, Alessandro

AU - Ferrante, Marc

AU - Vogelsang, Harald

AU - Hibi, Toshifumi

AU - Watanabe, Mamoru

AU - Lefebvre, Jessica

AU - Finney-Hayward, Tricia

AU - Sanchez Gonzalez, Yuri

AU - Doan, Thao T.

AU - Mostafa, Nael M.

AU - Ikeda, Kimitoshi

AU - Xie, Wangang

AU - Huang, Bidan

AU - Petersson, Joel

AU - Kalabic, Jasmina

AU - Robinson, Anne M.

AU - Sandborn, William J.

N1 - Funding Information: AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. The authors thank Lynn Randall (AbbVie) for contributing to data interpretation and James W. Butler, a former AbbVie employee, for contributing to statistical analysis and data interpretation. William Sandborn was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases–funded San Diego Digestive Diseases Research Center (P30 DK120515). Medical writing assistance, funded by AbbVie, was provided by Caroline W. Cazares, PhD, of JB Ashtin. Funding Information: AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. The authors thank Lynn Randall (AbbVie) for contributing to data interpretation and James W. Butler, a former AbbVie employee, for contributing to statistical analysis and data interpretation. William Sandborn was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases–funded San Diego Digestive Diseases Research Center (P30 DK120515). Medical writing assistance, funded by AbbVie, was provided by Caroline W. Cazares, PhD, of JB Ashtin. Julián Panés, MD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Jean-Frederic Colombel, MD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Geert R. D'Haens, MD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Stefan Schreiber, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Remo Panaccione, MD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Laurent Peyrin-Biroulet, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Edward V. Loftus Jr, MD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Silvio Danese, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Satoshi Tanida, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Yusuke Okuyama, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Edouard Louis, MD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Alessandro Armuzzi, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Marc Ferrante, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Harald Vogelsang, MD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Toshifumi Hibi, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Mamoru Watanabe, MD, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Jessica Lefebvre, MD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Tricia Finney-Hayward, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Yuri Sanchez Gonzalez, PhD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Thao T. Doan, MD (Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Nael M. Mostafa, PhD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Kimitoshi Ikeda, PhD (Data curation: Equal; Formal analysis: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Wangang Xie, PhD (Data curation: Equal; Formal analysis: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Bidan Huang, PhD (Conceptualization: Equal; Data curation: Equal; Formal analysis: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Joel Petersson, MD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Jasmina Kalabic, MD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Anne M. Robinson, PharmD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). William J. Sandborn, MD (Conceptualization: Equal; Data curation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal) 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. Publisher Copyright: © 2022 The Authors

PY - 2022/6

Y1 - 2022/6

N2 - 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.

AB - 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.

KW - Adalimumab

KW - Clinical Trial Result

KW - Inflammatory Bowel Disease

KW - Moderately to Severely Active Ulcerative Colitis

KW - Monoclonal Antibody

UR - http://www.scopus.com/inward/record.url?scp=85127544553&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85127544553&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2022.02.033

DO - 10.1053/j.gastro.2022.02.033

M3 - Article

C2 - 35227777

AN - SCOPUS:85127544553

SN - 0016-5085

VL - 162

SP - 1891

EP - 1910

JO - Gastroenterology

JF - Gastroenterology

IS - 7

ER -

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

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