Comparative Safety and Effectiveness of Vedolizumab to Tumor Necrosis Factor Antagonist Therapy for Ulcerative Colitis

Dana Lukin, David Faleck, Ronghui Xu, Yiran Zhang, Aaron Weiss, Satimai Aniwan, Siri Kadire, Gloria Tran, Mahmoud Rahal, Adam Winters, Shreya Chablaney, Jenna L. Koliani-Pace, Joseph Meserve, James P Campbell, Gursimran Kochhar, Matthew Bohm, Sashidhar Varma, Monika Fischer, Brigid Boland, Siddharth SinghRobert Hirten, Ryan Ungaro, Karen Lasch, Eugenia Shmidt, Vipul Jairath, David Hudesman, Shannon Chang, Arun Swaminath, Bo Shen, Sunanda Kane, Edward V. Loftus, Bruce E. Sands, Jean Frederic Colombel, Corey A. Siegel, William J. Sandborn, Parambir S. Dulai

Research output: Contribution to journalArticlepeer-review

Abstract

Background & Aims: We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice. Methods: A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist–naïve and –exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately. Results: A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist–naïve and −exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist−treated patients. However, in TNF-antagonist−naïve patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754). Conclusions: Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist−naïve patients.

Original languageEnglish (US)
JournalClinical Gastroenterology and Hepatology
DOIs
StateAccepted/In press - 2021

Bibliographical note

Funding Information:
Funding Parambir S. Dulai and Ronghui Xu had independence from funders for conduct of this study, had full access to all the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis. Takeda Pharmaceuticals provided funding for statistical support to analyze the data. Takeda Pharmaceuticals and associated employees had no access to patient level data and were not involved in data analyses. All data analyses were performed at the University of California San Diego by consortium investigators or statisticians, independent of Takeda Pharmaceuticals. Parambir S. Dulai is supported by an American Gastroenterology Association Research Scholar Award. This project was supported in part by the UCSD T32 training grant (DK 0070202; JM).

Funding Information:
Conflicts of interest These authors disclose the following: Dana Lukin reports consulting for AbbVie, Abgenomics, Celgene, Pfizer, Prometheus, and Takeda and educational grant support from AbbVie and Takeda. David Faleck reports travel support from Takeda. Jenna L. Koliani-Pace reports travel support from Takeda. Joseph Meserve 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, and AMAG Pharmaceuticals; and career development awards from the American College of Gastroenterology and Crohn’s and Colitis Foundation. Robert Hirten reports speaking or advisory boards for Takeda and Janssen. Ryan Ungaro is a consulting and/or advisory board member for Takeda, Pfizer, and Janssen. Karen Lasch is an employee of Takeda Pharmaceuticals, USA, Inc. Eugenia Shmidt reports travel support from Takeda. Vipul Jairaith reports consulting fees from AbbVie, Janssen, Takeda, Sandoz, Ferring, Pfizer, GlaxoSmithKline, Robarts Clinical Trials, Eli Lilly and Company , and Arena and speaker fees from Takeda, Ferring, Janssen, and Shire. David Hudesman reports consulting fees from AbbVie, Takeda, Janssen, and Pfizer. Shannon Chang reports consulting fees from Oshi. Arun Swaminath reports fellowship support from Janssen, AbbVie, and Pfizer and grant support from Pfizer. Bo Shen reports consulting for Janssen, Salix, AbbVie, Takeda, Theravance, and Robarts Clinical Trials. Sunanda Kane reports consulting for AbbVie, Merck, Spherix Health, Seres Pharmaceuticals, and Samsung Bioepis. Edward V. Loftus reports consulting for Janssen, Takeda, AbbVie, UCB, Amgen, Pfizer, Salix, Mesoblast, Eli Lilly and Company, Celgene, and CVS Caremark and research support from Janssen, Takeda, AbbVie, UCB, Amgen, Pfizer, Genentech, Gilead, Receptos, Celgene, MedImmune, Seres Therapeutics, and Robarts Clinical Trials. Bruce E. Sands reports consulting/advisory board or honorarium from 4D Pharma, AbbVie, Allergan Sales, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Capella BioScience, Celgene, EnGene, Ferring, Gilead, Janssen, Eli Lilly and Company, 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, and WebMD. Jean-Frederic Colombel reports consultant or advisory board member for AbbVie, Amgen, Boehringer Ingelheim , Arena Pharmaceuticals, Celgene Corporation , Celltrion, Enterome, Eli Lilly and Company, Ferring Pharmaceuticals , Genentech, Janssen, Medimmune, Merck & Co, Nextbiotix, Novartis Pharmaceuticals Corporation , Otsuka Pharmaceutical Development & Commercialization , Inc, Pfizer, Protagonist, Second Genome, Gilead, Seres Therapeutics, Shire, Takeda, and Theradiag; speaker for AbbVie, Ferring, Takeda, and Celgene Corporation; stock options from Intestinal Biotech Development and Genfit; and research grants from AbbVie, Takeda, and Janssen. Corey A. Siegel reports consulting/advisory board for AbbVie, Amgen, Celgene, Eli Lilly and Company, Janssen, Sandoz, Pfizer, Prometheus, Sebela, and Takeda; speaker for AbbVie, Janssen, Pfizer, and Takeda; grant support from Crohn’s and Colitis Foundation, AHRQ (1R01HS021747-01), AbbVie, Janssen, Pfizer, and Takeda; intellectual property from MiTest Health, LLC, and ColonaryConcepts, LLC; and equity interest from 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 and Company, 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, and 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, and Amgen; grants, personal fees, and non-financial support from Janssen; and grants from Broad Foundation , American College of Gastroenterology , and Exact Sciences. Parambir S. Dulai is on the steering committee for Takeda; does consulting for Takeda and Janssen; honorarium for speaker events from Takeda; travel support from Takeda and Janssen; and grant support from Takeda and Pfizer. The remaining authors disclose no conflicts.

Funding Information:
Conflicts of interest These authors disclose the following: Dana Lukin reports consulting for AbbVie, Abgenomics, Celgene, Pfizer, Prometheus, and Takeda and educational grant support from AbbVie and Takeda. David Faleck reports travel support from Takeda. Jenna L. Koliani-Pace reports travel support from Takeda. Joseph Meserve 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, and AMAG Pharmaceuticals; and career development awards from the American College of Gastroenterology and Crohn's and Colitis Foundation. Robert Hirten reports speaking or advisory boards for Takeda and Janssen. Ryan Ungaro is a consulting and/or advisory board member for Takeda, Pfizer, and Janssen. Karen Lasch is an employee of Takeda Pharmaceuticals, USA, Inc. Eugenia Shmidt reports travel support from Takeda. Vipul Jairaith reports consulting fees from AbbVie, Janssen, Takeda, Sandoz, Ferring, Pfizer, GlaxoSmithKline, Robarts Clinical Trials, Eli Lilly and Company, and Arena and speaker fees from Takeda, Ferring, Janssen, and Shire. David Hudesman reports consulting fees from AbbVie, Takeda, Janssen, and Pfizer. Shannon Chang reports consulting fees from Oshi. Arun Swaminath reports fellowship support from Janssen, AbbVie, and Pfizer and grant support from Pfizer. Bo Shen reports consulting for Janssen, Salix, AbbVie, Takeda, Theravance, and Robarts Clinical Trials. Sunanda Kane reports consulting for AbbVie, Merck, Spherix Health, Seres Pharmaceuticals, and Samsung Bioepis. Edward V. Loftus reports consulting for Janssen, Takeda, AbbVie, UCB, Amgen, Pfizer, Salix, Mesoblast, Eli Lilly and Company, Celgene, and CVS Caremark and research support from Janssen, Takeda, AbbVie, UCB, Amgen, Pfizer, Genentech, Gilead, Receptos, Celgene, MedImmune, Seres Therapeutics, and Robarts Clinical Trials. Bruce E. Sands reports consulting/advisory board or honorarium from 4D Pharma, AbbVie, Allergan Sales, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Capella BioScience, Celgene, EnGene, Ferring, Gilead, Janssen, Eli Lilly and Company, 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, and WebMD. Jean-Frederic Colombel reports consultant or advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Arena Pharmaceuticals, Celgene Corporation, Celltrion, Enterome, Eli Lilly and Company, Ferring Pharmaceuticals, Genentech, Janssen, Medimmune, Merck & Co, Nextbiotix, Novartis Pharmaceuticals Corporation, Otsuka Pharmaceutical Development & Commercialization, Inc, Pfizer, Protagonist, Second Genome, Gilead, Seres Therapeutics, Shire, Takeda, and Theradiag; speaker for AbbVie, Ferring, Takeda, and Celgene Corporation; stock options from Intestinal Biotech Development and Genfit; and research grants from AbbVie, Takeda, and Janssen. Corey A. Siegel reports consulting/advisory board for AbbVie, Amgen, Celgene, Eli Lilly and Company, Janssen, Sandoz, Pfizer, Prometheus, Sebela, and Takeda; speaker for AbbVie, Janssen, Pfizer, and Takeda; grant support from Crohn's and Colitis Foundation, AHRQ (1R01HS021747-01), AbbVie, Janssen, Pfizer, and Takeda; intellectual property from MiTest Health, LLC, and ColonaryConcepts, LLC; and equity interest from 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 and Company, 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, and 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, and Amgen; grants, personal fees, and non-financial support from Janssen; and grants from Broad Foundation, American College of Gastroenterology, and Exact Sciences. Parambir S. Dulai is on the steering committee for Takeda; does consulting for Takeda and Janssen; honorarium for speaker events from Takeda; travel support from Takeda and Janssen; and grant support from Takeda and Pfizer. The remaining authors disclose no conflicts.

Publisher Copyright:
© 2020 The Authors

Keywords

  • Biologics
  • Comparative Research
  • Health Outcomes

PubMed: MeSH publication types

  • Journal Article

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