Takeda announces results of pioneering Ulcerative Colitis study
Global biopharmaceutical company Takeda today announced the results of its pioneering VARSITY study into the effectiveness of two common therapies used to treat Ulcerative Colitis. Shared at the 14th Congress of the European Crohn’s and Colitis Organization (ECCO) in Copenhagen Denmark, the findings showed that the use of vedolizumab – a gut-selective biologic treatment, was more effective overall at tackling the illness when compared to adalimumab– a common anti-tumor therapy.
Specifically, the study found that by week 52 of treatment among patients with moderate to severely active ulcerative colitis, 31.3 percent of those receiving vedolizumab intravenously experienced clinical remission*, compared to 22.5 percent of patients receiving adalimumab via injection at week 52. In addition, 39.7 percent of patients treated with vedolizumab recorded mucosal healing** – a slowing of the disease’s progression, compared to 27.7 percent of those receiving adalimumab.
A non-statistically significant difference in favor of adalimumab was seen among patients who stopped taking oral corticosteroids – steroid hormones that are usually produced in the adrenal gland and were in clinical remission*** at week 52. Meanwhile, although the study was not conducted to compare the safety of the two treatments, patients treated with vedolizumab had a lower rate (62.7 percent) of adverse effects over 52 weeks compared to patients receiving adalimumab treatment (69.2 percent). Those treated with vedolizumab recorded a lower rate of infection (33.5 percent) compared to patients treated with adalimumab (43.5 percent). The rate of serious adverse events was also lower in vedolizumab-treated patients than adalimumab (11.0% vs. 13.7% respectively).
“The VARSITY study addresses critical questions concerning the selection of biologic therapy in ulcerative colitis. The goal of treatment of this disease is to achieve clinical remission and mucosal healing, and these results clearly highlight the benefits seen with vedolizumab versus adalimumab towards these important outcomes.” said Dr. Bruce E. Sands, primary investigator of the VARSITY study and Chief of both the Dr. Henry D. Janowitz Division of Gastroenterology at Mount Sinai Hospital, and the Icahn School of Medicine at Mount Sinai in New York.
Jeff Bornstein, M.D., Executive Medical Director, Takeda added, “The study gives physicians invaluable knowledge towards treatment decisions when starting biologic therapy. This is also the first time we have seen a direct comparison between two medicines with distinct modes of action in ulcerative colitis. This is an exciting time in the landscape of ulcerative colitis treatment, as head-to-head clinical data has not previously been available to guide treatment decisions around biologic therapies.”
The VARSITY study comprised a random selection of 769 patients, all of whom had shown an inadequate response with, loss of response to, or intolerance to corticosteroids, immunomodulators, or one TNF?-antagonist other than adalimumab before being enrolled.
Patients were randomly placed into one of two treatment groups – vedolizumab IV and placebo SC or adalimumab SC and placebo IV. Patients in the vedolizumab group were administered 300 mg of vedolizumab IV at weeks 0, 2, 6 and every 8 weeks after until week 46, along with placebo SC at week 0 and every 2 weeks until week 50. The adalimumab group were administered 160 mg of adalimumab SC at week 0, 80 mg at week 2 and 40 mg every 2 weeks until week 50, along with placebo IV at weeks 0, 2, 6 and every 8 weeks thereafter until week 46. Dose escalation was not permitted in either treatment arm during the study.1,
* Primary endpoint: Clinical remission is defined as a complete Mayo score of ?2 points and no individual subscore ?1 point.2
** Secondary endpoint: Mucosal healing is defined as Mayo endoscopic subscore of ?1 point. Mayo score: instrument designed to measure disease activity of ulcerative colitis.2
*** Secondary endpoint: Corticosteroid-free clinical remission is defined as patients using oral corticosteroids at baseline (week 0) who have discontinued oral corticosteroids and are in clinical remission at week 52.2
About Ulcerative Colitis
Ulcerative colitis (UC) is one of the most common forms of inflammatory bowel disease (IBD). UC is a chronic, relapsing, remitting, inflammatory condition of the gastrointestinal tract that is often progressive in nature, and involves the innermost lining of the large intestine., UC commonly presents with symptoms of abdominal discomfort and loose bowel movements, including blood or pus.5, The cause of UC 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 the condition.5,,
Vedolizumab is a gut-selective biologic and is approved as an intravenous (IV) formulation. 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). MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract. The alpha4beta7 integrin is expressed on a subset of circulating white blood cells.10 These cells have been shown to play a role in mediating the inflammatory process in ulcerative colitis (UC) and Crohn’s disease (CD).10,, By inhibiting alpha4beta7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.10
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 (TNF?) antagonist.9 Vedolizumab IV has been granted marketing authorization in over 60 countries, including the United States and European Union, with more than 260,000 patient years of exposure to date.
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 (TNF?) 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 (TNF?) antagonist.
Important Safety Information
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.
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.
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 ?4?7 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.
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.
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.
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), Neuroscience, and Rare Diseases. 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.
For more information, visit https://www.takeda.com
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 An efficacy and safety study of vedolizumab intravenous (IV) compared to adalimumab subcutaneous (SC) in participants with ulcerative colitis. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT02497469. Last updated: February 18, 2019. Last Accessed: February 2019.
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 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.
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