Introduction
VERDICT, a randomised treat-to-target trial, aimed to determine the optimal treatment target to reduce ulcerative colitis (UC)-related complications.
Aims & Methods
Adults (N=672) with moderate to severe UC (Mayo rectal bleeding subscore [RBS] ≥ 1; Mayo endoscopic score [MES] ≥ 2) were randomised to treatment targeting corticosteroid-free (CSF) symptomatic (Mayo RBS = 0; group 1) remission, CSF symptomatic and endoscopic (MES ≤ 1) remission (group 2), or CSF symptomatic, endoscopic, and histologic (Geboes score < 2B.0) remission (group 3). Treatment was escalated to randomised targets using vedolizumab-based algorithms. The primary outcome compared time to UC-related complication (a composite of hospitalisation, colectomy, use of rescue therapy, treatment-related, and other UC-related complications) up to 80 weeks after target achievement between groups 3 and 1.
Results
A total of 665 patients received vedolizumab (184, 220 and 261 in groups 1, 2, and 3). Baseline characteristics were similar across groups. A total of 56.1% of patients were male, 88.7% were of white race, mean (SD) age was 41.4 (14.6) years, disease duration was 8.0 (8.3) years, faecal calprotectin concentration was 1992.3 (2075.5) mg/kg, C reactive protein concentration was 8.4 (14.1) mg/L, the Inflammatory Bowel Disease Questionnaire score was 128.1 (34.8), the Robarts Histopathology Score was 18.3 (7.9), 62.6% of patients had MES = 3, 48.1% were receiving corticosteroids, and 9.9% were receiving immunosuppressants. Additional disease characteristics are included in the Table. Four hundred patients achieved their assigned target. Fifty-one UC-related complications occurred, with use of rescue therapy being the most frequent. Time to UC-related complication was longer in group 3 versus group 1 (hazard ratio 0.33 [95% confidence interval 0.17-0.67]; P=0.0014) and in group 2 versus group 1 (0.30 [0.14-0.64]; P=0.004). Time to UC-related complication was similar between groups 2 and 3 (1.10 [0.45-2.69]; P=0.8023), but 79.2% (99/125) of patients in group 2 achieved histologic as well as endoscopic remission. Adverse event rates were similar across groups and unaffected by treatment escalation and more frequent vedolizumab dosing to achieve more stringent targets.
Table. Additional baseline disease characteristics of the patients
| Group 1
(n=184)
| Group 2
(n=220)
| Group 3
(n=261)
| Overall
(N=665)
|
Tumour necrosis factor antagonist use, n (%)
|
|
|
|
|
| Never
| 142 (77.2)
| 174 (79.1)
| 219 (83.9)
| 535 (80.5)
|
| Past
| 39 (21.2)
| 42 (19.1)
| 36 (13.8)
| 117 (17.6)
|
| Current
| 3 (1.6)
| 4 (1.8)
| 6 (2.3)
| 13 (2.0)
|
Prior advanced therapy use, n (%)
| 52 (28.3)
| 52 (23.6)
| 44 (16.9)
| 148 (22.3)
|
Treatment algorithm, n (%)
|
|
|
|
|
| A (not on UC therapy)
| 1 (0.5)
| 1 (0.5)
| 2 (0.8)
| 4 (0.6)
|
| B (on non-advanced UC therapy)
| 131 (71.2)
| 167 (75.9)
| 215 (82.4)
| 513 (77.1)
|
| C (on TNF antagonist, ustekinumab, tofacitinib)
| 52 (28.3)
| 52 (23.6)
| 44 (16.9)
| 148 (22.3)
|
Conclusion
Treat-to-target strategies incorporating stringent composite endpoints were associated with longer time to UC-related complication than symptom-based management in VERDICT, supporting histologic and endoscopic remission as feasible and clinically relevant treatment goals (NCT04259138).
Disclosure
Vipul Jairath reports consulting fees/advisory boards/speaker fees from AbbVie, Alimentiv, Amgen, Anaptys Bio, Asahi Kasei, Asieris, Astra Zeneca, Attovia, Blackbird Labs, BMS, Boehringer Ingelheim, Biomebank, Cabaletta, Caldera, Calluna, Catalytic Health, Celltrion, Ensho, Enthera, Enveda, Exeliome Biosciences, Ferring, Fresenius Kabi, Gilead, Granite Bio, GSK, Janssen, Lilly, Merck, Mobius, Mountainfield, MRM Health, Nxera, Orbimed, Organon, OSE Immunotherapeutics, Palisade Bio, Pendopharm, Pfizer, PharmaNest, Pioneering Medicine, PIPr Therapeutics, Roche/Genentech, Sanofi, SCOPE, Shattuck Labs, Sorriso, Spyre, Synedgen, Takeda, Teva, Tillotts, Throne Scientific, Tr1X Inc., Union Therapeutics, Ventus, Ventyx, Vividion, Xencor, and Zealand Pharma.
Jean-Frederic Colombel reports research grants from AbbVie, Janssen Pharmaceuticals, Takeda, Prometheus and Bristol Myers Squibb; payment for lectures from AbbVie, Roche, Takeda, Celltrion; receiving consulting fees from AbbVie, Amgen, AnaptysBio, Allergan, Apini, Arena Pharmaceuticals, Astellas, Boehringer Ingelheim, Bristol Myers Squibb, Candidrx, Celgene, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Genentech-Roche (DSMB), Glaxo Smith Kline, Janssen Pharmaceuticals, Kaleido Biosciences, Immunic, Iterative Scopes, Landos, Microba Life Science, Merck, Mirador, Novartis, Otsuka Pharmaceutical, Owkin, Pfizer, Protagonist Therapeutics, Sanofi (DSMB), Sun Pharma, Takeda, Teva (DSMB), TiGenix, and stock options in Intestinal Biotech Development.
Geert R. D’Haens reports serving as an advisor and/or speaker for AbbVie, Abivax, Agomab, Alimentiv, Astrazeneca, Biora, Bristol Meiers Squibb, Boehringer Ingelheim, Cabaletta, Celltrion, Dova Health, Equillium, Ferring, Eli Lilly, Galapagos, Falk, Glaxo Smith Kline, Index Pharmaceuticals, Johnson and Johnson, Mage Biologics, Merck, Mirador, MRM Health, Odyssey, Onco3R, Pfizer, Prometheus biosciences, Prometheus laboratories, Procise diagnostics, Protagonist, Sanofi, Setpoint, Shattuck, Spyre, Takeda, Tillotts, UCB, and Zip Bio.
Guangyong Zou reports consulting fees from Alimentiv, Inc.
Shaji Sebastian reports consulting fees from Takeda, AbbVie, Merck, Ferring, Pharmacosmos, Warner Chilcott, Johnson & Johnson Innovative Medicine, Dr Falk Pharma, Biohit, TriGenix, Celgene, Celltrion and Tillotts Pharma outside the submitted work; payment or honoraria from AbbVie, Takeda, Celltrion, Pfizer, Biogen, AbbVie, Johnson & Johnson Innovative Medicine, Merck, Warner Chilcott, Eli Lilly , Celltrion and Dr Falk Pharma outside the submitted work, and holds research grants from AbbVie, Takeda, Johnson and Johnson, Amgen, Pfizer and Tillotts Pharma.
Mark S. Silverberg reports speaker, advisory board, and consulting fees as well as research funding from AbbVie, Janssen, Merck, Pfizer, Takeda, Ferring, Organon, Novartis, Gilead, Galapagos, Amgen, Celltrion, Eli Lilly. Mirador, SCOPE.
Gordon W. Moran reports grant income from Astra Zeneca, Pfizer, Jansen, Bristol Myers Squibb; consultancy for Pfizer, Jansen, Takeda, Bristol Myers Squibb, AbbVie, Motilent, Alimentiv Inc, RedEx Pharma, Tillotts, Satisfai Health, and Dova Health.
Severine Vermeire reports grant support from AbbVie, J&J, Pfizer, Galapagos and Takeda; consulting and/or speaking fees from AbbVie, Abivax, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillotts Pharma AG and Zealand Pharma.
William J. Sandborn reports consulting fees from Alimentiv, Forbion, Shoreline Biosciences; stock or stock options from Abivax, Eli Lilly, Prometheus Biosciences, Prometheus Laboratories, Shoreline Biosciences, Mirador Therapeutics, Ventyx Biosciences; and employee at Mirador Therapeutics andVentyx Biosciences. Spouse: Merck – employee; Abivax – stock; Eli Lilly – stock; Mirador Therapeutics – employee, stock, stock options; Prometheus Biosciences - employee, stock, stock options; Prometheus Laboratories – stock, stock options, consultant, Triveni Bio – board of directors, consulting fees, stock options; Ventyx Biosciences –stock, stock options.
Christian Agboton and Itzel Romo Bautista are employees of Takeda and hold Takeda stock/stock options.
Maria Klopocka reports payment for lectures from Janssen, Takeda, Ferring, AbbVie, Janssen, Recordati and travel/accommodation/meeting expenses from Takeda, and AbbVie.
Peter Bossuyt reports grant support for research from AbbVie, EG; consulting fees from AbbVie, Bristol Meyers Squibb, CIRC, Galapagos, Janssen, Jeito capital, Lilly, Pentax, Pfizer, PSI-CRO, Roche, Takeda, Tetrameros; speaker fees from AbbVie, AMC ICP, Amgen, Bristol Myers Squibb, Celltrion, Dr Falk Benelux, EG, Galapagos, Globalport, Lilly, Medtalks, Materia Prima, Pentax, and Springer Media.
Jaroslaw Kierkus reports grant from Nestle.
Melanie Beaton reports advisory board or consultancy fees from AbbVie, Celltrion, Ferring, Janssen, Novo Nordisk, Pfizer, and Takeda. She has participated in clinical trials with AbbVie, Novo Nordisk, Gilead, Takeda, Janssen, Pfizer and Astra Zeneca.
Rima Petroniene reports fees from Janssen, AbbVie, Takeda, Merck, Roche.
Jack Satsangi reports travel support and lecture fees from Takeda and J&J.
Terry Ponich reports advisory board fees from Celltrion, Eli Lilly and Pfizer. Currently an investigator on clinical research studies for Abivax, Alimentiv, Eli Lilly, Merck, Sanofi, Spyre and Takeda.
Alessandro Armuzzi reports consulting/advisory board fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, Merck, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillotts Pharma; speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Fresenius Kabi, Galapagos, Gilead, Janssen, Lionhealth, Merck, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Sanofi, Takeda, Teva.
Najm Soofi reports consulting fees from Boxer Capital and advisory board fees from Ferring Pharmaceuticals.
Marc Ferrante reports research grants from AbbVie, EG Pharma, Celltrion, Janssen, Pfizer, Takeda and Viatris; consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, Merck Sharp and Dohme, MRM Health, Numab Therapeutics AG, Pfizer, Takeda, Thermo Fisher and ZipBio; speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare and Viatris.
Jeremy Picard, Julie Sigler, Luiza Nita, Lisa M. Shackelton and Gabriela Radulescu report employment by Alimentiv, Inc.
Fernando Magro reports lecture fees from AbbVie, Abivax, Adacyte, Alfasigma, Amgen, Bristol Myers Squibb (BMS), CelltrionFerring, FalK,Fresenius Kabi, Galapagos, Gilead, GSK , Janssen, Lilly, Laboratorios Vitoria, MSD, OM Pharma, Pfizer, Roche, Sandoz, Sanofi, Takeda, Teva, and Tillotts.
Rocio Sedano reports consulting fees from AbbVie, Alimentiv, Celltrion, Pendopharm and Takeda; speaker’s fees from AbbVie and Takeda.
Christopher Ma reports consulting fees from AbbVie, Alimentiv, Amgen, Anaptys Bio, AVIR Pharma Inc, Bristol Myers Squibb, Celldex Therapeutics Inc., Celltrion, Domain Therapeutics, Eupraxia, Eli Lilly, Ferring, First Tracks Biotherapeutics, Forte Biosciences, Fresenius Kabi, Gilead, Janssen, McKesson, Merck, Mirador Therapeutics, Mozart Therapeutics, NOA Therapeutics, Pendopharm, Pfizer, Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Eli Lilly, Ferring, Pfizer.
Jurij Hanžel reports speaker’s fees from AbbVie, Eli Lilly, Johnson & Johnson, and Takeda; consulting fees from Alimentiv Inc.
Nicholas Powell reports speaker, advisory consultant and or research grants from AbbVie, Alimentiv, Allergan, Astra-Zeneca, Bristol-Myers Squibb, Celgene, Celltrion, Dr Falk Pharma UK Ltd, Ferring, Galapagos, GSK, Janssen, MSD, Roche, Pfizer, Sobi, Takeda, Tillotts and Vifor.
Saurabh Mehandru reports research grants from Genentech and Takeda; payment for lectures from Adacyte Therapeutics; and consulting fees from AbbVie, Adacyte Therapeutics, Alimentiv, Attovia, BMS, Cabaletta, Caldera, Georgia Immune, Janssen, Merck and Novartis Pharmaceuticals.
Silvio Danese reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor, Anaptysbio, Apini, Banook, Biolojic, Cabaletta Bio, Caldera Therapeutics, Cesas, Elasmogen, Gilead, Granite Bio, Heymay, Novartis, Onco3r, Ono Pharma, Sorriso Therapeuticals, Spyre, Tr1x, Alfasigma, Sanofi, Janssen, Genentech, Abivax, Ose Immunotherapeutics, Bayer, Samsung Bioepis; lecture fees from AbbVie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda.
Bruce E Sands reports honoraria for consulting from Aclaris Therapeutics, Adaxion Therapeutics, Adiso Therapeutics, Agomab Therapeutics, Alfasigma, Alimentiv, Amgen, AnaptysBio, AstraZeneca, Attovia Therapeutics, Biolojic Design, BiomeBank, Biora Therapeutics, Boehringer-Ingelheim, Caldera Therapeutics, Cellarity, Cytoki Pharma, Disc Medicine, Eil Lilly & Company, Ensho Therapeutics, Enthera, Enveda Biosciences, Equilium, Evommune, Ferring, Fzata, Galapagos, Genentech (Roche), Genesis Therapeutics, Gilead Sciences, GlaxoSmithKline, Globalport, Ignite Biomedical, Imedex, Imhotex, Immunitas Therapeutics, Immunyx Pharma, Kallyope, Kyowa Kirin, LifeMine Therapeutics, Merck & Co., Merck Sharp & Dohme, Microba, Microbiotica, Mirador Therapeutics, Mitsubishi Tanabe Pharma, Mobius Care, Morphic Therapeutic, MRM Health, Nexus Therapeutics, Nimbus Discovery, Novartis, Numab Therapeutics, Odyssey Therapeutics, ONO Pharmaceutical, OSE Immunotherapeutics, Palisade Bio, Pioneering Medicines Explorations, Prometheus Biosciences, Protagonist Therapeutics, Q32 Bio, Quotient Therapeutics, Rasayana Therapeutics, Recludix Pharma, Reistone Biopharma, Sanofi, Slate Bio, Sorriso Pharmaceuticals, Spyre Therapeutics, Synlogic, Target RWE, Televant, Teva, Thetis Pharmaceuticals, SRT Therapeutics, TR1X, Trex Bio, Union Therapeutics, VectivBio, Vedanta Biosciences, Vividion Therapeutics, and Xencor; honoraria for consulting and speaking and other support from AbbVie, Abivax, Bristol Myers Squibb, Celltrion, Eli Lilly & Company, Genentech (Roche), J&J Innovative Medicine/Janssen, Merck & Company, Pfizer, Takeda, and Teva; honoraria for consulting, stock options from Caldera Therapeutics, Mirador Therapeutics and SRT Therapeutics; and stock from Doximity.
Stefan Schreiber reports fees as a speaker and/or consultant and/or scientific advisor from AbbVie, Amgen, Arena, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Falk, Ferring, Fresenius Kabi, Galápagos, Gilead, I-MAB, Janssen/J&J, Lilly, MSD, Mylan, Novartis, Pfizer, Protagonist, Provention Bio, Roche, Sandoz/Hexal, Shire, Takeda, Ventyx.
David T. Rubin reports grant support from Takeda and Pfizer; and has served as a consultant for AbbVie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Celltrion, Clostrabio, Eli Lilly & Co., Genentech (Roche) Inc., Gilead, Iterative Health, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Throne, Vedanta Biosciences, and Ventyx.
Simon Travis reports grants/research support from AbbVie, Celgene, Celsius, ECCO, Galapagos, GSK, Helmsley Trust, IOIBD, Janssen, Lilly, Pfizer, Takeda, 35Bio, Vifor, and Norman Collisson Foundation; consulting fees from AbbVie, Alimentiv, Apexian, Apollo, AstraZeneca, BMS, Clario; Cosmo, Dova Health, Endpoint Health, EQrX; Equillium, Ferring, Galapagos, Genentech/Roche, Gilead, GSK, Janssen, Iterative Health, Lilly, Mestag, Mirae-AI, Montai, Pfizer, Phesi, Prologue, Protagonist, Sanofi, Spyre, Takeda, Teva, Theravance, Tr1X Bio, Xencor; and UCB; speaker fees from BMS, Ferring, GSK, Janssen, Lilly, Pfizer, Sun Pharma, Takeda; and share options from Dova Health Inc and Mirae-AI. Patents include GB2612362.0 and GB2613340.5.
Laurent Peyrin-Biroulet reports consulting fees from AbbVie, Abivax, Adacyte, Alimentiv, Alfasigma, Amgen, Apini , Banook, BMS, Boehringher, Celltrion, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, GSK, Hemay, Iterative Health, Janssen, Lilly, LifeMine, Luzsana, Medac, Mirador, Morphic, MSD, Nordic Pharma, Novartis, Oddifact, Oncodesign Precision Medicine, Coultreon (ex-Onco3R), ONO Pharma, OSE Immunotherapeuthics, Palisade Bio, Par' Immune, Pfizer, Prometheus, Roche, Roivant, Samsung, Sandoz, Sanofi, Sorriso, Spyre, Takeda, Teva, ThirtyfiveBio, Tillotts, Vectivbio, Vedanta, and Ventyx; stock/stock options from Iterative Health, Oragen, Pharmanest, and Thetis; lecture fees from AbbVie, Alfasigma, Amgen, Biogen, Celltrion, Dr Falk, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, Medac, MSN Labs, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Takeda, and Tillotts.
