Retrospective Real-World Comparative Analysis Highlights Safety of Vedolizumab and Anti-TNFα Therapies in Biologic-Naïve Patients with Ulcerative Colitis or Crohn’s Disease
- Latest real-world data presented at UEG Week 2019 complements the extensive body of clinical evidence for the gut-selective biologic vedolizumab in biologic-naïve patients with moderately to severely active ulcerative colitis or Crohn’s disease
Osaka, JAPAN, October 21, 2019 – Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced results from a retrospective chart review study (EVOLVE), which investigated the likelihood of serious adverse events and serious infections with vedolizumab and anti-tumor necrosis factor-alpha (anti-TNFα) therapies in biologic-naïve patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD) in real-world clinical practice. These data were announced in an oral presentation at UEG Week 2019, held in Barcelona, Spain.
Data from over 1,000 biologic-naïve patients with UC or CD receiving vedolizumab or an anti-TNFα therapy (adalimumab, infliximab, golimumab, or certolizumab pegol) were collected, with the incidence rate (per 100 person-years) for serious adverse events and serious infections estimated per cohort. The incidence rates for the first occurrence of a serious adverse event (vedolizumab: 4.6 [3.5-6.8]; anti-TNFα: 10.3 [9.5-14.9]) and serious infections (vedolizumab: 1.4 [0.8-2.5]; anti-TNFα: 2.6 [1.7-4.3]) were estimated to be lower with vedolizumab treatment.[i] Also, gastrointestinal infections were estimated to be lower in vedolizumab-treated vs. anti-TNFα-treated patients (1.1% vs. 4.3%, respectively, p<0.01).1 Similar trends were observed when results were segmented by UC and CD.1*
“While retrospective chart reviews have limitations and are not conclusive, real-world evidence can enhance our understanding of the performance of treatments in clinical practice, providing valuable information to assist physicians in the selection of appropriate therapy for patients. Sharing the latest real-world evidence, such as the EVOLVE study, with scientific and clinical communities, forms an integral part of Takeda’s ongoing commitment towards improving patient care,” said Michelle Luo, PhD, Head of Global Outcomes Research-Gastroenterology, Takeda.
The EVOLVE study is one of nine Takeda vedolizumab abstracts accepted for presentation at the annual UEG Week congress, with new data being presented from clinical studies that assess the efficacy and safety of vedolizumab, as well as new evaluations to understand the role of clinical decision support tools in the management of inflammatory bowel disease.
* Data revised following abstract acceptance
About the EVOLVE Study
The EVOLVE study was a retrospective chart review of real-world data in biologic-naïve patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD) treated with vedolizumab or anti-tumor necrosis factor-alpha (anti-TNFα) therapies. Patients had initiated treatment with vedolizumab or anti-TNFα therapies (adalimumab, infliximab, golimumab, or certolizumab pegol) between May 2014 and March 2018 and were followed for ≥six months. Evidence was collected from 1,095 biologic-naïve patients from 42 sites in Canada, Greece and the United States; 598 were treated with vedolizumab (UC=380; CD=218), and 497 were treated with anti-TNFα therapies (UC=224; CD=273).1 A Cox proportional hazards model adjusted for baseline patient characteristics was used to compare incidence rates between treatment cohorts.[ii]
A retrospective chart review is a type of research design in which patient medical records are collected from real-world clinical practice to answer research questions.[iii],[iv] The data evaluated were collected before the research had begun, and therefore were not originally intended for investigative purposes nor to answer specific research questions. While retrospective chart reviews are important for advancing physician understanding of the performance of treatments in clinical practice, the records reviewed may not be complete and as such chart reviews can be more prone to bias as compared to prospective studies.4
About Ulcerative Colitis and Crohn’s Disease
Ulcerative colitis (UC) and Crohn’s disease (CD) are two of the most common forms of inflammatory bowel disease (IBD).[v] Both UC and CD are chronic, relapsing, remitting, inflammatory conditions of the gastrointestinal tract that are often progressive in nature.[vi],[vii] UC only involves the large intestine as opposed to CD, which can affect any part of the GI tract from mouth to anus.[viii],[ix] CD can also affect the entire thickness of the bowel wall, while UC only involves the innermost lining of the large intestine.7,8 UC commonly presents with symptoms of abdominal discomfort and loose bowel movements, including blood or pus.8,[x] CD commonly presents with symptoms of abdominal pain, diarrhea, and weight loss.6 The cause of UC or CD is not fully understood; however, recent research suggests hereditary, genetic, environmental factors, and/or an abnormal immune response to microbial antigens in genetically predisposed individuals can lead to UC or CD.8,[xi],[xii]
About Entyvio® (vedolizumab)
Vedolizumab is a gut-selective biologic and is approved as an intravenous (IV) formulation.[xiii],[xiv] It is a humanized monoclonal antibody designed to specifically antagonize the alpha4beta7 integrin, inhibiting the binding of alpha4beta7 integrin to intestinal mucosal addressin cell adhesion molecule 1 (MAdCAM-1), but not vascular cell adhesion molecule 1 (VCAM-1).[xv] MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract.[xvi] The alpha4beta7 integrin is expressed on a subset of circulating white blood cells.15 These cells have been shown to play a role in mediating the inflammatory process in ulcerative colitis (UC) and Crohn’s disease (CD).15,[xvii],[xviii] By inhibiting alpha4beta7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.15
Vedolizumab IV is approved for the treatment of adult patients with moderately to severely active UC and CD, who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNFα) antagonist.13,14 Vedolizumab IV has been granted marketing authorization in over 60 countries, including the United States and European Union, with more than 330,000 patient years of exposure to date.[xix]
Vedolizumab is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNFα) antagonist.
Vedolizumab is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNFα) antagonist.
[i] Yarur A, Mantzaris GJ, Kopylov U, et al. Real-world safety of vedolizumab and anti-TNF therapies in biologic-naïve ulcerative colitis and Crohn’s disease patients: Results from the EVOLVE study. Presented at UEG Week 2019. Oral presentation OP005.
[ii] Yarur A, Mantzaris G, Silverberg M, et al. P573 Real-world effectiveness and safety of vedolizumab and anti-TNF in biologic-naive ulcerative colitis patients: Results from the EVOLVE study. J Crohns Colitis. 2019;13:S400–S401.
[iii] Vassar M and Holzmann M. The retrospective chart review: important methodological considerations. J Educ Eval Health Prof. 2013;10:12.
[iv] Panacek EA. Performing chart review studies. Air Med J. 2007;26:206-10.
[v] Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369:1627-1640.
[vi] Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380:1590-1605.
[vii] Torres J, Billioud V, Sachar DB, et al. Ulcerative colitis as a progressive disease: the forgotten evidence. Inflamm Bowel Dis. 2012;18:1356-1363.
[viii] Ordas I, Eckmann L, Talamini M, et al. Ulcerative colitis. Lancet. 2012;380:1606-1619.
[ix] Feuerstein JD, Cheifetz AS. Crohn’s disease: Epidemiology, diagnosis and management. Mayo Clin Proc. 2017;92:1088-1103.
[x] Sands BE. From symptom to diagnosis: clinical distinctions among various forms of intestinal inflammation. Gastroenterology. 2004;126:1518-1532.
[xi] Henckaerts L, Pierik M, Joossens M, et al. Mutations in pattern recognition receptor genes modulate seroreactivity to microbial antigens in patients with inflammatory bowel disease. Gut. 2007;56:1536-1542.
[xii] Kaser A, Zeissig S, Blumberg RS. Genes and environment: How will our concepts on the pathophysiology of IBD develop in the future? Dig Dis. 2010;28:395-405.
[xiv] Entyvio EPAR _ 20/02/2019 Entyvio - EMEA/H/C/002782_ European Medicines Agency - Entyvio _ Annex I- Summary of product characteristics. Committee For Medicinal Products For Human Use. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/entyvio. Last updated: April 2019. Last accessed: October 2019.
[xv] Soler D, Chapman T, Yang LL, et al. The binding specificity and selective antagonism of vedolizumab, an anti-α4β7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009;330:864-875.
[xvi] Briskin M, Winsor-Hines D, Shyjan A, et al. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Am J Pathol. 1997;151:97‑110.
[xvii] Eksteen B, Liaskou E, Adams DH. Lymphocyte homing and its roles in the pathogenesis of IBD. Inflamm Bowel Dis. 2008;14:1298‑1312.
[xviii] Wyant T, Fedyk E, Abhyankar B. An overview of the mechanism of action of the monoclonal antibody vedolizumab. J Crohns Colitis. 2016;10:1437-1444.
[xix] Takeda Data on File. 2019.
- Takeda Pharmaceutical Company Limited
- Takeda Pharmaceutical Company Limited