OSAKA, Japan-Monday 21 October 2019 [ AETOS Wire ]
For more information, visit https://www.takeda.com
(BUSINESS WIRE) -- 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.1 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.2
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.3,4 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).5 Both
UC and CD are chronic, relapsing, remitting, inflammatory conditions of
the gastrointestinal tract that are often progressive in nature.6,7 UC only involves the large intestine as opposed to CD, which can affect any part of the GI tract from mouth to anus.8,9 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.8,10 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.8,11,12
About Entyvio® (vedolizumab)
Vedolizumab is a gut-selective biologic and is approved as an intravenous (IV) formulation.13,14 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).15 MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract.16 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).15,17,18 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.19
Therapeutic Indications
Ulcerative colitis
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.
Crohn’s disease
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.
Important Safety Information
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Special warnings and special precautions for use
Vedolizumab
should be administered by a healthcare professional prepared to manage
hypersensitivity reactions, including anaphylaxis, if they occur.
Appropriate monitoring and medical support measures should be available
for immediate use when administering vedolizumab. Observe patients
during infusion and until the infusion is complete.
Infusion-related reactions
In
clinical studies, infusion-related reactions (IRR) and hypersensitivity
reactions have been reported, with the majority being mild to moderate
in severity. If a severe IRR, anaphylactic reaction, or other severe
reaction occurs, administration of vedolizumab must be discontinued
immediately and appropriate treatment initiated (e.g., epinephrine and
antihistamines). If a mild to moderate IRR occurs, the infusion rate can
be slowed or interrupted and appropriate treatment initiated (e.g.,
epinephrine and antihistamines). Once the mild or moderate IRR subsides,
continue the infusion. Physicians should consider pre-treatment (e.g.,
with antihistamine, hydrocortisone and/or paracetamol) prior to the next
infusion for patients with a history of mild to moderate IRR to
vedolizumab, in order to minimize their risks.
Infections
Vedolizumab
is a gut-selective integrin antagonist with no identified systemic
immunosuppressive activity. Physicians should be aware of the potential
increased risk of opportunistic infections or infections for which the
gut is a defensive barrier. Vedolizumab treatment is not to be initiated
in patients with active, severe infections such as tuberculosis,
sepsis, cytomegalovirus, listeriosis, and opportunistic infections until
the infections are controlled, and physicians should consider
withholding treatment in patients who develop a severe infection while
on chronic treatment with vedolizumab. Caution should be exercised when
considering the use of vedolizumab in patients with a controlled chronic
severe infection or a history of recurring severe infections. Patients
should be monitored closely for infections before, during and after
treatment. Before starting treatment with vedolizumab, screening for
tuberculosis may be considered according to local practice. Some
integrin antagonists and some systemic immunosuppressive agents have
been associated with progressive multifocal leukoencephalopathy (PML),
which is a rare and often fatal opportunistic infection caused by the
John Cunningham (JC) virus. By binding to the α4β7 integrin expressed on
gut-homing lymphocytes, vedolizumab exerts an immunosuppressive effect
specific to the gut. Although no systemic immunosuppressive effect was
noted in healthy subjects, the effects on systemic immune system
function in patients with inflammatory bowel disease are not known.
Healthcare professionals should monitor patients on vedolizumab for any
new onset or worsening of neurological signs and symptoms, and consider
neurological referral if they occur. If PML is suspected, treatment with
vedolizumab must be withheld; if confirmed, treatment must be
permanently discontinued. Typical signs and symptoms associated with PML
are diverse, progress over days to weeks, and include progressive
weakness on one side of the body, clumsiness of limbs, disturbance of
vision, and changes in thinking, memory, and orientation leading to
confusion and personality changes. The progression of deficits usually
leads to death or severe disability over weeks or months.
Malignancies
The
risk of malignancy is increased in patients with ulcerative colitis and
Crohn’s disease. Immunomodulatory medicinal products may increase the
risk of malignancy.
Prior and concurrent use of biological products
No
vedolizumab clinical trial data are available for patients previously
treated with natalizumab. No clinical trial data for concomitant use of
vedolizumab with biologic immunosuppressants are available. Therefore,
the use of vedolizumab in such patients is not recommended.
Vaccinations
Prior
to initiating treatment with vedolizumab all patients should be brought
up to date with all recommended immunizations. Patients receiving
vedolizumab may receive non-live vaccines (e.g., subunit or inactivated
vaccines) and may receive live vaccines only if the benefits outweigh
the risks.
Adverse reactions include: nasopharyngitis,
headache, arthralgia, upper respiratory tract infection, bronchitis,
influenza, sinusitis, cough, oropharyngeal pain, nausea, rash, pruritus,
back pain, pain in extremities, pyrexia, fatigue and anaphylaxis.
Please consult with your local regulatory agency for approved labeling in your country.
For U.S. audiences, please see the full Prescribing Information including Medication Guide for ENTYVIO®.
For EU audiences, please see the Summary of Product Characteristics (SmPC) for ENTYVIO®.
Takeda’s Commitment to Gastroenterology
Gastrointestinal
(GI) diseases can be complex, debilitating and life-changing.
Recognizing this unmet need, Takeda and our collaboration partners have
focused on improving the lives of patients through the delivery of
innovative medicines and dedicated patient disease support programs for
over 25 years. Takeda aspires to advance how patients manage their
disease. Additionally, Takeda is leading in areas of gastroenterology
associated with high unmet need, such as inflammatory bowel disease,
acid-related diseases and motility disorders. Our GI Research &
Development team is also exploring solutions in celiac disease and liver
diseases, as well as scientific advancements through microbiome
therapies.
About Takeda Pharmaceutical Company Limited
Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK)
is a global, values-based, R&D-driven biopharmaceutical leader
headquartered in Japan, committed to bringing Better Health and a
Brighter Future to patients by translating science into
highly-innovative medicines. Takeda focuses its R&D efforts on four
therapeutic areas: Oncology, Gastroenterology (GI), Rare Diseases, and
Neuroscience. We also make targeted R&D investments in
Plasma-Derived Therapies and Vaccines. We are focusing on developing
highly innovative medicines that contribute to making a difference in
people's lives by advancing the frontier of new treatment options and
leveraging our enhanced collaborative R&D engine and capabilities to
create a robust, modality-diverse pipeline. Our employees are committed
to improving quality of life for patients and to working with our
partners in health care in approximately 80 countries and regions.
References
1 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.
2 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.
3 Vassar M and Holzmann M. The retrospective chart review: important methodological considerations. J Educ Eval Health Prof. 2013;10:12.
4 Panacek EA. Performing chart review studies. Air Med J. 2007;26:206-10.
5 Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369:1627-1640.
6 Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380:1590-1605.
7 Torres J, Billioud V, Sachar DB, et al. Ulcerative colitis as a progressive disease: the forgotten evidence. Inflamm Bowel Dis. 2012;18:1356-1363.
8 Ordas I, Eckmann L, Talamini M, et al. Ulcerative colitis. Lancet. 2012;380:1606-1619.
9 Feuerstein JD, Cheifetz AS. Crohn’s disease: Epidemiology, diagnosis and management. Mayo Clin Proc. 2017;92:1088-1103.
10 Sands BE. From symptom to diagnosis: clinical distinctions among various forms of intestinal inflammation. Gastroenterology. 2004;126:1518-1532.
11 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.
12 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.
13 Entyvio Prescribing Information. Available at: https://general.takedapharm.com/ENTYVIOPI. Last updated: May 2019. Last accessed: October 2019.
14 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. https://www.ema.europa.eu/en/medicines/human/EPAR/entyvio. Last updated: April 2019. Last accessed: October 2019.
15 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.
16 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.
17 Eksteen B, Liaskou E, Adams DH. Lymphocyte homing and its roles in the pathogenesis of IBD. Inflamm Bowel Dis. 2008;14:1298‑1312.
18 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.
19 Takeda Data on File. 2019.
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Contacts
Media outside Japan
Luke Willats
luke.willats@takeda.com
+41-44-555-1145
Japanese Media
Tatsuhiro Kanoo
tatsuhiro.kanoo@takeda.com
+81 (0) 3-3278-2095
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