Abstract
Background: Direct comparisons are lacking between vedolizumab and tumour necrosis factor (TNF)-antagonist therapy in Crohn's disease (CD). Aim: To compare safety and effectiveness of vedolizumab and TNF-antagonist therapy in adult CD patients. Methods: Retrospective observational cohort (May 2014–December 2017) propensity score-weighted comparison of vedolizumab vs TNF-antagonist therapy (infliximab, adalimumab, certolizumab) in CD. Propensity scores were weighted for age, prior treatments, disease complications, extent and severity, steroid dependence, and concomitant immunosuppressive drug use. The primary outcome was comparative risk for infections or non-infectious serious adverse events (requiring antibiotics, antivirals, antifungals, hospitalisation, or treatment discontinuation, or resulting in death). Secondary comparative effectiveness outcomes were clinical remission (resolution of CD-related symptoms), steroid-free clinical remission and endoscopic remission (absence of ulcers/erosions). Results: We included 1266 patients (n = 659 vedolizumab). Rates of non-infectious serious adverse events (odds ratio [OR] 0.072, 95% confidence interval [CI] 0.012-0.242), but not serious infections (OR 1.183, 95% CI 0.786-1.795), were significantly lower with vedolizumab vs TNF-antagonist therapy. Safety comparisons for non-infectious serious adverse events remained significant after adjusting for differences in duration of exposure. No significant difference was observed between vedolizumab and TNF-antagonist therapy for clinical remission (hazard ratio [HR] 0.932, 95% CI 0.707-1.228), steroid-free clinical remission (HR 1.250, 95% CI 0.677-2.310) or endoscopic remission (HR 0.827, 95% CI 0.595-1.151). TNF-antagonist therapy was associated with higher treatment persistence compared with vedolizumab. Conclusions: There was a lower risk of non-infectious serious adverse events, but not serious infections, with vedolizumab vs TNF-antagonist therapy, with no significant difference for achieving disease remission.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 669-681 |
| Number of pages | 13 |
| Journal | Alimentary Pharmacology and Therapeutics |
| Volume | 52 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 2020 |
Bibliographical note
Funding Information:: Matthew Bohm, Ronghui Xu, Yiran Zhang, Sashidhar Varma, Monika Fischer, Siri Kadire, Gloria Tran, Mahmoud Rahal, Satimai Aniwan, Aaron Weiss, Gursimran Kochhar, James P. Campbell, Adam Winters, and Shreya Chablaney have no potential conflicts of interest to disclose. Joseph Meserve reports travel support from Takeda. Jenna L. Koliani‐Pace reports travel support from Takeda. Brigid Boland receives research support from Takeda and Janssen. Siddharth Singh reports research support from AbbVie, Pfizer; consulting for Pfizer, AbbVie, Takeda, AMAG Pharmaceuticals; career development awards from the American College of Gastroenterology and Crohn's and Colitis Foundation. David Faleck reports travel support from Takeda. Robert Hirten reports speaking or advisory boards for Takeda, Janssen. Ryan Ungaro is a consulting and/or advisory board member for Takeda, Pfizer, and Janssen. Eugenia Shmidt reports travel support from Takeda. Karen Lasch is an employee of Takeda Pharmaceuticals, USA, Inc Vipul Jairaith reports consulting fees from AbbVie, Janssen, Takeda, Sandoz, Ferring, Pfizer, GlaxoSmithKline, Robarts Clinical Trials, Eli Lilly, Arena; speaker fees from: Takeda, Ferring, Janssen, Shire. David Hudesman reports consulting fees from AbbVie, Takeda, Janssen, Pfizer. Shannon Chang reports consulting fees from Oshi. Dana Lukin, reports consulting for AbbVie, Janssen, Salix. Arun Swaminath reports fellowship support from Janssen, AbbVie, Pfizer; grant support from Pfizer. Bruce E. Sands reports consulting/advisory board or honorarium: 4D Pharma, AbbVie, Allergan Sales, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Capella BioScience, Celgene, EnGene, Ferring, Gilead, Janssen, Lilly, Lyndra, MedImmune, Oppilan Pharma, Otsuka, Palatin Technologies, Pfizer, Progenity, Rheos Pharmaceuticals, Seres Therapeutics, Synergy Pharmaceuticals, Takeda, Target PharmaSolutions, Theravance Biopharma R&D, Inc, TiGenix, Vivelix Pharmaceuticals, WebMD. Jean‐Frederic Colombel reports consultant or advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Arena Pharmaceuticals, Celgene Corporation, Celltrion, Enterome, Eli Lilly, Ferring Pharmaceuticals, Genentech, Janssen and Janssen, Medimmune, Merck & Co., Nextbiotix, Novartis Pharmaceuticals Corporation, Otsuka Pharmaceutical Development & Commercialization, Inc, Pfizer, Protagonist, Second Genome, Gilead, Seres Therapeutics, Shire, Takeda, Theradiag; speaker for AbbVie, Ferring, Takeda, Celgene Corporation; stock options: Intestinal Biotech Development, Genefit; research grants: AbbVie, Takeda, Janssen and Janssen. Sunanda Kane reports consulting for AbbVie, Merck, Spherix Health, Seres Pharmaceuticals, Samsung Bioepis. Edward V. Loftus reports consulting for Janssen, Takeda, AbbVie, UCB, Amgen, Pfizer, Salix, Mesoblast, Eli Lilly, Celgene, and CVS Caremark; research support from Janssen, Takeda, AbbVie, UCB, Amgen, Pfizer, Genentech, Gilead, Receptos, Celgene, MedImmune, Seres Therapeutics, and Robarts Clinical Trials. Bo Shen reports consulting for Janssen, Salix, AbbVie, Takeda, Theravance, Robarts Clinical Trials. Corey A. Siegel reports consulting/advisory board AbbVie, Amgen, Celgene, Lilly, Janssen, Sandoz, Pfizer, Prometheus, Sebela, Takeda; Speaker AbbVie, Janssen, Pfizer, Takeda; Grant support Crohn's and Colitis Foundation, AHRQ (1R01HS021747‐01), AbbVie, Janssen, Pfizer, Takeda; Intellectual property MiTest Health, LLC, and ColonaryConcepts, LLC; Equity interest MiTest Health and ColonaryConcepts. William J. Sandborn reports personal fees from Kyowa Hakko Kirin, Millennium Pharmaceuticals, Celgene Cellular Therapeutics, Santarus, Salix Pharmaceuticals, Catabasis Pharmaceuticals, Vertex Pharmaceuticals, Warner Chilcott, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Sigmoid Biotechnologies, Tillotts Pharma, Am Pharma BV, Dr August Wolff, Avaxia Biologics, Zyngenia, Ironwood Pharmaceuticals, Index Pharmaceuticals, Nestle, Lexicon Pharmaceuticals, UCB Pharma, Orexigen, Luitpold Pharmaceuticals, Baxter Healthcare, Ferring Research Institute, Novo Nordisk, Mesoblast Inc, Shire, Ardelyx Inc, Actavis, Seattle Genetics, MedImmune (AstraZeneca), ActoGeniX NV, Lipid Therapeutics GmbH, Eisai, Qu Biologics, Toray Industries Inc, Teva Pharmaceuticals, Eli Lilly, Chiasma, TiGenix, Adheron Therapeutics, Immune Pharmaceuticals, Celgene, Arena Pharmaceuticals; personal fees from Ambrx Inc, Akros Pharma, Vascular Biogenics, Theradiag, Forward Pharma, Regeneron, Galapagos, Seres Health, Ritter Pharmaceuticals, Theravance, Palatin, Biogen, University of Western Ontario (owner of Robarts Clinical Trials); grants and personal fees from Prometheus Laboratories, AbbVie, Gilead Sciences, Boehringer Ingelheim, Amgen, Takeda, Atlantic Pharmaceuticals, Bristol‐Myers Squibb, Genentech, GlaxoSmithKline, Pfizer, Nutrition Science Partners, Receptos, Amgen; grants, personal fees and non‐financial support from Janssen; grants from Broad Foundation, American College of Gastroenterology, Exact Sciences. Parambir S. Dulai is on the steering committee for Takeda; does consulting for Takeda, Janssen; honorarium for speaker events Takeda; travel support Takeda, Janssen; grant support Takeda, Pfizer. Declaration of personal interests
Funding Information:
Takeda Pharmaceuticals provided funding for statistical support to analyse the data; however, Takeda Pharmaceuticals and associated employees did not have access to any of the data. Data were collected at each site individually and transferred as de-identified data to the coordinating centre (University of California San Diego) for compilation and analyses. All data analyses were performed at the University of California San Diego by consortium investigators or statisticians, independent of Takeda Pharmaceuticals. Declaration of personal interests: Matthew Bohm, Ronghui Xu, Yiran Zhang, Sashidhar Varma, Monika Fischer, Siri Kadire, Gloria Tran, Mahmoud Rahal, Satimai Aniwan, Aaron Weiss, Gursimran Kochhar, James P. Campbell, Adam Winters, and Shreya Chablaney have no potential conflicts of interest to disclose. Joseph Meserve reports travel support from Takeda. Jenna L. Koliani-Pace reports travel support from Takeda. Brigid Boland receives research support from Takeda and Janssen. Siddharth Singh reports research support from AbbVie, Pfizer; consulting for Pfizer, AbbVie, Takeda, AMAG Pharmaceuticals; career development awards from the American College of Gastroenterology and Crohn's and Colitis Foundation. David Faleck reports travel support from Takeda. Robert Hirten reports speaking or advisory boards for Takeda, Janssen. Ryan Ungaro is a consulting and/or advisory board member for Takeda, Pfizer, and Janssen. Eugenia Shmidt reports travel support from Takeda. Karen Lasch is an employee of Takeda Pharmaceuticals, USA, Inc Vipul Jairaith reports consulting fees from AbbVie, Janssen, Takeda, Sandoz, Ferring, Pfizer, GlaxoSmithKline, Robarts Clinical Trials, Eli Lilly, Arena; speaker fees from: Takeda, Ferring, Janssen, Shire. David Hudesman reports consulting fees from AbbVie, Takeda, Janssen, Pfizer. Shannon Chang reports consulting fees from Oshi. Dana Lukin, reports consulting for AbbVie, Janssen, Salix. Arun Swaminath reports fellowship support from Janssen, AbbVie, Pfizer; grant support from Pfizer. Bruce E. Sands reports consulting/advisory board or honorarium: 4D Pharma, AbbVie, Allergan Sales, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Capella BioScience, Celgene, EnGene, Ferring, Gilead, Janssen, Lilly, Lyndra, MedImmune, Oppilan Pharma, Otsuka, Palatin Technologies, Pfizer, Progenity, Rheos Pharmaceuticals, Seres Therapeutics, Synergy Pharmaceuticals, Takeda, Target PharmaSolutions, Theravance Biopharma R&D, Inc, TiGenix, Vivelix Pharmaceuticals, WebMD. Jean-Frederic Colombel reports consultant or advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Arena Pharmaceuticals, Celgene Corporation, Celltrion, Enterome, Eli Lilly, Ferring Pharmaceuticals, Genentech, Janssen and Janssen, Medimmune, Merck & Co., Nextbiotix, Novartis Pharmaceuticals Corporation, Otsuka Pharmaceutical Development & Commercialization, Inc, Pfizer, Protagonist, Second Genome, Gilead, Seres Therapeutics, Shire, Takeda, Theradiag; speaker for AbbVie, Ferring, Takeda, Celgene Corporation; stock options: Intestinal Biotech Development, Genefit; research grants: AbbVie, Takeda, Janssen and Janssen. Sunanda Kane reports consulting for AbbVie, Merck, Spherix Health, Seres Pharmaceuticals, Samsung Bioepis. Edward V. Loftus reports consulting for Janssen, Takeda, AbbVie, UCB, Amgen, Pfizer, Salix, Mesoblast, Eli Lilly, Celgene, and CVS Caremark; research support from Janssen, Takeda, AbbVie, UCB, Amgen, Pfizer, Genentech, Gilead, Receptos, Celgene, MedImmune, Seres Therapeutics, and Robarts Clinical Trials. Bo Shen reports consulting for Janssen, Salix, AbbVie, Takeda, Theravance, Robarts Clinical Trials. Corey A. Siegel reports consulting/advisory board AbbVie, Amgen, Celgene, Lilly, Janssen, Sandoz, Pfizer, Prometheus, Sebela, Takeda; Speaker AbbVie, Janssen, Pfizer, Takeda; Grant support Crohn's and Colitis Foundation, AHRQ (1R01HS021747-01), AbbVie, Janssen, Pfizer, Takeda; Intellectual property MiTest Health, LLC, and ColonaryConcepts, LLC; Equity interest MiTest Health and ColonaryConcepts. William J. Sandborn reports personal fees from Kyowa Hakko Kirin, Millennium Pharmaceuticals, Celgene Cellular Therapeutics, Santarus, Salix Pharmaceuticals, Catabasis Pharmaceuticals, Vertex Pharmaceuticals, Warner Chilcott, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Sigmoid Biotechnologies, Tillotts Pharma, Am Pharma BV, Dr August Wolff, Avaxia Biologics, Zyngenia, Ironwood Pharmaceuticals, Index Pharmaceuticals, Nestle, Lexicon Pharmaceuticals, UCB Pharma, Orexigen, Luitpold Pharmaceuticals, Baxter Healthcare, Ferring Research Institute, Novo Nordisk, Mesoblast Inc, Shire, Ardelyx Inc, Actavis, Seattle Genetics, MedImmune (AstraZeneca), ActoGeniX NV, Lipid Therapeutics GmbH, Eisai, Qu Biologics, Toray Industries Inc, Teva Pharmaceuticals, Eli Lilly, Chiasma, TiGenix, Adheron Therapeutics, Immune Pharmaceuticals, Celgene, Arena Pharmaceuticals; personal fees from Ambrx Inc, Akros Pharma, Vascular Biogenics, Theradiag, Forward Pharma, Regeneron, Galapagos, Seres Health, Ritter Pharmaceuticals, Theravance, Palatin, Biogen, University of Western Ontario (owner of Robarts Clinical Trials); grants and personal fees from Prometheus Laboratories, AbbVie, Gilead Sciences, Boehringer Ingelheim, Amgen, Takeda, Atlantic Pharmaceuticals, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Pfizer, Nutrition Science Partners, Receptos, Amgen; grants, personal fees and non-financial support from Janssen; grants from Broad Foundation, American College of Gastroenterology, Exact Sciences. Parambir S. Dulai is on the steering committee for Takeda; does consulting for Takeda, Janssen; honorarium for speaker events Takeda; travel support Takeda, Janssen; grant support Takeda, Pfizer.
Publisher Copyright:
© 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd
