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

- New meta-analysis provides a comprehensive view of real-world data and furthers understanding ofEntyvio 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® (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-naïve 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® (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 (α4β7) integrin is expressed on a subset of circulating white blood cells. Vedolizumab specifically binds to the α4β7 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 (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 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 α4β7 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 including Medication Guide for ENTYVIO®. For EU audiences, please see theSummary of Product Characteristics (SmPC) for ENTYVIO®. 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.