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Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial

Research output: Contribution to journalArticlepeer-review

SEAVUE Study Group, Bruce E. Sands, Peter M. Irving

Original languageEnglish
Pages (from-to)2200-2211
Number of pages12
JournalThe Lancet
Volume399
Issue number10342
DOIs
Published11 Jun 2022

Bibliographical note

Funding Information: BES reports consulting fees from 4D Pharma, AbbVie, Abivax, Allergan, Amgen, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Baxalta Bioscience India, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Capella Bioscience, Celltrion Healthcare, ClostraBio, Entera, Evommune, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, GossamerBio, Hoffmann-La Roche, HMP Acquisition, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kallyope, Lilly, Merck & Co, MiroBio, Morphic Therapeutic, Oppilan Pharma, OSE Immunotherapeutics, Otsuka, Palatin Technologies, Pfizer, Progenity, Prometheus Laboratories, Prometheus Biosciences IBD, Protagonist Therapeutics, Q32 Bio, Redhill Biopharma, Rheos Medicines, Salix Pharmaceuticals, Seres Therapeutics, Shire, Sienna Biopharmaceuticals, Sun Pharma, Surrozen, Takeda, TARGET RWE, Teva, TLL Therapeutics, USWM Enterprises, Viela Bio, Vivelix Pharmaceuticals; grants and consulting fees from Arena Pharmaceuticals, Celgene, and Theravance Biopharma; consulting fees and stock options from Ventyx Biosciences; and stock options from Vivante Health. PMI reports lecture fees from AbbVie, Celgene, Falk Pharma, Ferring, Janssen, MSD, Pfizer, Sapphire Medical, Sandoz, Shire, Takeda, Tillots, and Warner Chilcott; financial support for research from MSD, Pfizer, and Takeda; and advisory fees from AbbVie, Arena, Genentech, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Prometheus, Roche, Sandoz, Samsung Bioepis, Takeda, Topivert, VH2, Vifor Pharma, and Warner Chilcott. TH, JLI, L-LG, CG, and AG report employment with Immunology Global Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson or Janssen Scientific Affairs, a wholly owned subsidiary of Johnson & Johnson, and stock ownership in Johnson & Johnson. MA reports consulting or lecture fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Ferring, Genentech, Gilead, IQVIA, Janssen, Novartis, Pfizer, Roche, Takeda, and Tillots; and grant support from Innate Pharma, Janssen, Takeda, and Genentech/Roche. SD reports consulting or lecture fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion Healthcare, Enthera, Ferring Pharmaceuticals, Gilead Sciences, Hospira, Inotrem, Janssen, Johnson & Johnson, Lilly, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB, and Vifor International. SBH reports grant support and fees for consulting, lectures, and serving on an advisory board from AbbVie, Janssen, and Takeda; consulting or advisory board fees from Allergan, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Ferring, Genentech, Gilead, Merck, Novartis, Pfizer, Protagonist, Receptos, Salix, Samsung Bioepis, Seres Therapeutics, TiGenix, and Vhsquared; and grant support from AbbVie, Celgene, Boehringer Ingelheim, Gilead, Janssen, Pfizer, and Takeda. VJ reports consulting fees from AbbVie, Alimentiv, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Lilly, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, and Topivert; and speaker's fees from AbbVie, Ferring, Galapagos, Janssen, Pfizer, Shire, and Takeda. TK reports lecture and consulting fees from AbbVie, Allmiral, Amgen, Arena, Bristol Myers Squibb, Celgene, Celltrion, Ferring, Falk, Gilead, Galapagos, Janssen, Merkle, Pfizer, Takeda, and Tillots. JDL reports consulting fees from Arena Pharmaceuticals, AbbVie, Bridge Biotherapeutics, Bristol Myers Squibb, Entasis Therapeutics, Gilead, Janssen, Lilly, Merck, Nestle Health Science, Pfizer, Protagonist Therapeutics, Samsung Bioepis, Scipher Medicine, and UCB; and research grants from AbbVie, Janssen, and Takeda. EVL Jr reports consulting fees from AbbVie, Amgen, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Calibr, Celgene, Genentech, Gilead, Gossamer Bio, Iterative Scopes, Janssen, Lilly, Morphic, Ono Pharma, Pfizer, Protagonist, Scipher Medicine, Sun Pharma, Surrozen, Takeda, and UCB; and research support from AbbVie, Bristol Myers Squibb, Celgene, Genentech, Gilead, Gossamer Bio, Janssen, Pfizer, Receptos, Robarts Clinical Trials, Takeda, Theravance, and UCB. EM reports participation as an investigator in trials sponsored by Janssen. RP reports consulting fees from AbbVie, Abbott, Alimentiv, Amgen, Arena, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Merck, Mylan, Oppilan 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, Ferring, Gilead Sciences, Janssen, Lilly, Merck, Pfizer, Roche, Sandoz, Shire, and Takeda; research or educational support from AbbVie, Ferring, Janssen, Pfizer, and Takeda; and has served on advisory boards for AbbVie, Amgen, Arena, Bristol Myers Squibb, Celgene, Celltrion, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Merck, Mylan, Oppilan Pharma, Pandion Pharma, Pfizer, Sandoz, Shire, Sublimity Therapeutics, Theravance, and Takeda. ES reports grant support from AbbVie, AstraZeneca, Celgene, Crohn's and Colitis Foundation, Genentech, Janssen Research & Development, New York Crohn's Foundation, Pfizer, Seres Therapeutics, and UCB; consulting fees from AbbVie, Abgenomics, Crohn's and Colitis Foundation, Evidera, GI Health Foundation, Janssen, Protagonist, Seres, and Takeda; stock ownership in Gilead; and speaker fees from GI Health Foundation and Prime Therapeutics. OBS reports participation as an investigator in trials sponsored by Janssen. WJS reports grants from AbbVie, Aviva, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Takeda, and TheraVance Biopharma; consulting fees from AbbVie, Abivax, Admirx, Alfa sigma, Alimentiv, Alivio Therapeutics, Allakos, Allergan, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Avexegen Therapeutics, Bausch Health (Salix), BeiGene, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Celgene, Celltrion, Cellularity, Conatus, Cosmo Pharmaceuticals, Equillium, Escalier Biosciences, Ferring, Forbion, Genentech/Roche, Gilead Sciences, Glenmark Pharmaceuticals, Gossamer Bio, Immunic (Vital Therapies), Incyte, Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyowa Kirin Pharmaceutical Research, Kyverna Therapeutics, Landos Biopharma, Lilly, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Oppilan Pharma (acquired by Ventyx Biosciences), Otsuka, Pandion Therapeutics, Paul Hastings, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonists Therapeutics, Provention Bio, Reistone Biopharma, Ritter Pharmaceuticals, Seres Therapeutics, Shanghai Pharma Biotherapeutics, Shire, Shoreline Biosciences, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, Surrozen, Takeda, Theravance Biopharma, Thetis Pharmaceuticals, Tigenix, Tillotts Pharma, UCB Pharma, Vendata Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals, Vivreon Biosciences, and Zealand Pharma; stock or stock options from Allakos, BeiGene, Gossamer Bio, Oppilan Pharma (acquired by Ventyx Biosciences), Prometheus Biosciences, Prometheus Laboratories, Progenity, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences, and Vivreon Biosciences; and employment at Shoreline Biosciences. Funding Information: The study was funded by Janssen Scientific Affairs. Holly Capasso-Harris (Certara Synchrogenix, Wilmington, DE, USA) provided writing and editorial assistance under the direction of the authors in accordance with Good Publications Practice guidelines. Writing assistance was funded by Janssen Scientific Affairs. Tony Ma (Janssen Scientific Affairs, Horsham, PA, USA) provided assistance with data analysis. Omoniyi J Adedokun (Janssen Research & Development, Spring House, PA, USA) provided assistance with data interpretation. Publisher Copyright: © 2022 Elsevier Ltd

King's Authors

Abstract

Background: Active-comparator trials are important to inform patient and physician choice. We aimed to evaluate the efficacy and safety of monotherapy with either ustekinumab or adalimumab in biologic-naive patients with moderately to severely active Crohn's disease. Methods: We conducted a randomised, double-blind, parallel-group, active-comparator, phase 3b trial (SEAVUE) at 121 hospitals or private practices in 18 countries. We included biologic-naive patients aged 18 years or older with moderately to severely active Crohn's disease and a Crohn's Disease Activity Index (CDAI) score of 220–450, who had not responded to or were intolerant to conventional therapy (or were corticosteroid dependent) and had at least one ulcer of any size at baseline endoscopic evaluation. Eligible patients were randomly assigned (1:1; via an interactive web response system) to receive ustekinumab (approximately 6 mg/kg intravenously on day 0, then 90 mg subcutaneously once every 8 weeks) or adalimumab (160 mg on day 0, 80 mg at 2 weeks, then 40 mg once every 2 weeks, subcutaneously) through week 56. Study treatments were administered as monotherapy and without dose modifications. Patients, investigators, and study site personnel were masked to treatment group assignment. The primary endpoint was the proportion of patients who were in clinical remission (CDAI score <150) at week 52 in the intention-to-treat population (ie, all patients who were randomly assigned to a treatment group). This trial is registered with ClinicalTrials.gov, NCT03464136, and EudraCT, 2017-004209-41. Findings: Between June 28, 2018, and Dec 12, 2019, 633 patients were assessed for eligibility and 386 were enrolled and randomly assigned to receive ustekinumab (n=191) or adalimumab (n=195). 29 (15%) of 191 patients in the ustekinumab group and 46 (24%) of 195 in the adalimumab group discontinued study treatment before week 52. There was no significant difference between the ustekinumab and adalimumab groups in the occurrence of the primary endpoint; at week 52, 124 (65%) of 191 patients in the ustekinumab group versus 119 (61%) of 195 in the adalimumab group were in clinical remission (between-group difference 4%, 95% CI –6 to 14; p=0·42). Safety for both groups was consistent with previous reports. Serious infections were reported in four (2%) of 191 patients in the ustekinumab group and five (3%) of 195 in the adalimumab group. No deaths occurred through week 52 of the study. Interpretation: Both ustekinumab and adalimumab monotherapies were highly effective in this population of biologic-naive patients, with no difference in the primary outcome between the drugs. Funding: Janssen Scientific Affairs.

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