PR70819

Meta-Analysis Using Real-World Data Evaluates Safety Profile of Entyvio(R) (vedolizumab) in Patients with Moderate to Severe Ulcerative Colitis or Crohn's Disease

OSAKA, November 1, 2017 /PRNewswire=KYODO JBN/ -

       - New meta-analysis provides a comprehensive view of real-world data and

furthers understanding of Entyvio as an important treatment option for patients

with ulcerative colitis or Crohn's disease  

    Takeda Pharmaceutical Company Limited (TSE: 4502) ("Takeda") today

announced the presentation of real-world evidence from two analyses evaluating

the safety profile of Entyvio(R) (vedolizumab), during the 25th United European

Gastroenterology (UEG) Week in Barcelona, Spain (October 28-November 1). It

includes a systematic review and meta-analysis of real-world safety outcomes

reported for Entyvio in ulcerative colitis (UC) or Crohn's disease (CD), as

well as a database analysis of the real-world use of immunosuppressive (IM)

therapy in people living with inflammatory bowel disease (IBD) who initiated

Entyvio treatment in the U.S.

    A systematic review and meta-analysis of real-world outcomes screening 218

published studies from MEDLINE-, Cochrane-, and EMBASE-indexed publications and

conference abstracts from May 1, 2014-January 10, 2017 examined safety events

reported after use of Entyvio in patients with UC or CD. A total of 33 studies

reported data on 2,857 Entyvio-treated patients (CD: 1,532; UC: 829) over an

Entyvio exposure/follow-up period ranging 0.5-18 months. In the meta-analysis,

pooled adverse event (AE) rates in Entyvio-treated patients were reported for

infections, serious AEs and serious infections. These reported rates were

consistent with previous vedolizumab clinical trial results in patients with

moderate to severe UC or CD and support the long-term safety profile of Entyvio

in clinical practice.

    "Real-world data furthers our understanding of the efficacy and safety

signals we see in placebo-controlled registration trials, which have strict

selection criteria and may not be illustrative of the patient population seen

in clinical practice. A meta-analysis adds stability to such real-world

observations, especially when based on very large patient numbers. In this

case, vedolizumab real-world data were systematically collected and analyzed

with the rates of serious infections, infusion-related reactions and

malignancies consistent with data previously reported in clinical trials in

patients with moderate to severe UC or CD," said Stefan Schreiber, M.D., Ph.D.,

Professor of Medicine and Gastroenterology, Translational Inflammation

Research, Christian Albrechts University, Kiel, Germany.  

    Results from a second U.S-specific analysis assessing the real-world use of

immunosuppressives (IM) across a total of 567 patients, identified via The

Explorys Universe database, also provide information on the safety profile of

Entyvio. Of the 567 patients (58.6% female; 41.4% male), 68.4% had CD and 31.6%

had UC. The mean age at index was 44 and on average, patients initiated

vedolizumab 4.5 years following their initial diagnosis. The findings report,

in real-world clinical practice, of the 45.4% of patients without a history of

IM therapy, 87% of patients treated with Entyvio were not on IM therapy during

follow-up. Of the 54.6% of patients with a history of IM therapy, 61% of

patients treated with Entyvio were not on IM during maintenance treatment

during follow-up. In this analysis, lower rates of healthcare resource

utilization were observed among patients without a history of IM use.

    "These data provide additional insight on the usage patterns, long-term

safety profile and outcomes of Entyvio use in real-world clinical practice,"

said Mona Khalid, Senior Director, Head of Evidence and Value Generation,

Takeda Pharmaceuticals. "We look forward to the continued expansion of our body

of knowledge on the safety profile of Entyvio treatment in ulcerative colitis

and Crohn's disease, and are pleased to present these real-world results at the

UEG Week in Barcelona."

    In addition to these real-world analyses, other Takeda-sponsored posters

presented at the UEG Week meeting include evaluations of post-marketing safety,

risk factors for postoperative infection following lower gastrointestinal

surgery, treatment discontinuation, flares and hospitalizations among

biologic-naive IBD patients, as well as post-hoc analyses of GEMINI 1, a

pivotal Phase 3 placebo-controlled study of Entyvio

induction and maintenance treatment in patients with moderately to severely

active UC. For a full list of poster titles and authors,

visit http://www.ueg.eu/week/programme/scientific-programme.

    About Entyvio(R) (vedolizumab)

    Vedolizumab is a prescription medicine approved for adults with moderate to

severe ulcerative colitis (UC) or Crohn's disease (CD). In people with UC and

CD, there's an increased number of inflammatory white blood cells entering the

mucosal lining of the bowel. The presence of these inflammatory cells can lead

to the symptoms most commonly seen in people who have UC or CD. Vedolizumab is

designed to reduce this inflammation by blocking the movement of the white

blood cells into the inflamed gut tissue. Mucosal addressin cell adhesion

molecule 1 (MAdCAM-1) is preferentially expressed on the endothelial lining of

blood vessels in the lymphoid tissue of the bowel. The alpha4beta7

(alpha4beta7) integrin is expressed on a subset of circulating white blood

cells. Vedolizumab specifically binds to the alpha4beta7 integrin and blocks

its interaction with MAdCAM-1, therefore inhibiting the white blood cells from

entering the inflamed gut tissue, thus decreasing inflammation.

    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). Both UC and CD are chronic,

relapsing, remitting, inflammatory conditions of the gastrointestinal (GI)

tract that are often progressive in nature. UC only involves the large

intestine as opposed to CD which can affect any part of the GI tract from mouth

to anus. CD can also affect the entire thickness of the bowel wall, while UC

only involves the innermost lining of the large intestine. UC commonly presents

with symptoms of abdominal discomfort, loose bowel movements, including blood

or pus. CD commonly presents with symptoms of abdominal pain, diarrhea and

weight loss. The cause of UC or CD is not fully understood, however recent

research suggests hereditary, genetics, environmental factors and/or an

abnormal immune response to microbial antigens in genetically predisposed

individuals can lead to UC or CD.

    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 (TNFalpha) 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 (TNFalpha) 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 equipped 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 all 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 alpha4beta7 integrin expressed on

gut-homing lymphocytes, vedolizumab exerts an immunosuppressive effect on 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. No cases of PML were reported in

clinical studies of vedolizumab however, 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. Caution should be exercised when considering the use

of vedolizumab in these patients. 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, and Fatigue.

    Please consult with your local regulatory agency for approved labeling in

your country.

    For U.S. audiences, please see the full Prescribing Information

[http://general.takedapharm.com/content/file.aspx?FileTypeCode=ENTYVIOPI&cacheRa

ndomizer=16fe4788-e18e-4f60-bd42-ec16de9d5fc9 ]

including Medication Guide

[http://general.takedapharm.com/content/file.aspx?filetypecode=ENTYVIOMG&Country

Code=US&LanguageCode=EN&cacheRandomizer=854644a6-db66-4a7b-8761-77c0a8f06456 ]

for ENTYVIO(R).

    For EU audiences, please see the Summary of Product Characteristics (SmPC)

[http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information

/human/002782/WC500168528.pdf ] for ENTYVIO(R).

    Takeda's Commitment to Gastroenterology

    More than 70 million people worldwide are impacted by gastrointestinal (GI)

diseases, which can be complex, debilitating and life-changing. Takeda is

driven to improving the lives of patients with GI diseases through innovative

medicines, dedicated patient disease management support and the evolution of

the healthcare environment. Takeda is leading in gastroenterology through the

delivery of innovative medicines in areas associated with high unmet needs,

such as inflammatory bowel disease, GI acid-related diseases and GI motility

disorders. Our GI research & development team is also exploring solutions in

celiac disease and nonalcoholic steatohepatitis (NASH), as well as scientific

advancements through microbiome therapies. With more than 25 years of

experience in this area, our broad approach to treating many diseases that

impact the GI system and our global network of collaborators, Takeda aims to

advance how patients manage their disease.

    About Takeda Pharmaceutical Company  

    Takeda Pharmaceutical Company Limited is a global, R&D-driven

pharmaceutical company committed to bringing better health and a brighter

future to patients by translating science into life-changing medicines. Takeda

focuses its research efforts on oncology, gastroenterology and central nervous

system therapeutic areas. It also has specific development programs in

specialty cardiovascular diseases as well as late-stage candidates for

vaccines. Takeda conducts R&D both internally and with partners to stay at the

leading edge of innovation. New innovative products, especially in oncology and

gastroenterology, as well as its presence in emerging markets, fuel the growth

of Takeda. More than 30,000 Takeda employees are committed to improving quality

of life for patients, working with our partners in health care in more than 70

countries. For more information, visit http://www.takeda.com/news.

SOURCE: Takeda Pharmaceutical Company Limited