Disease Background
Crohn disease is a chronic form of IBD that can affect any part of the GI tract, but most commonly affects the ileum (i.e., small intestine), colon (i.e., beginning of the large intestine), and rectum. Common GI symptoms experienced by patients with CD include abdominal pain, rectal bleeding, fatigue, vomiting, diarrhea, perianal disease, weight loss, and bloating.1,2 Inflammation associated with CD can also manifest outside the GI tract, affecting the joints, eyes, and skin of the patient. Complications associated with CD can include fever, malnutrition, weight loss, anemia, bowel obstructions, fistulas, anal fissures, intra-abdominal and other abscesses, and ulcers.2,3 In addition, patients with colonic CD have been shown to have an increased risk of developing colon cancer.2 According to the Canadian Gastro-Intestinal Epidemiology Consortium, the predicted prevalence of CD in 2018 was 368 per 100,000 population, thus there are approximately 135,000 Canadians living with CD.4,5 Based on patient group input for this review, CD has a profound effect on physical, emotional, and social well-being. The classification of disease severity in CD suggested by the American College of Gastroenterology is provided in .
Classification of Disease Severity in Crohn Disease.
Standards of Therapy
Selection of medical therapy is based on the location, extent, phenotype, and severity of disease.3 Currently there is no cure for CD, and the therapeutic goals include inducing and maintaining clinical and endoscopic remission, reducing the need for long-term corticosteroid use, and preventing the development of colon cancer. Several drug classes are used in the treatment of CD, including aminosalicylates, immunosuppressants (e.g., azathioprine, cyclosporine, methotrexate, and 6-mercaptopurine), corticosteroids (e.g., prednisone), TNF alpha antagonists (e.g., infliximab and adalimumab), IL inhibitors, and integrin inhibitors (e.g., vedolizumab).3,11 With the exception of the TNF alpha antagonists and vedolizumab, all are commonly referred to as conventional therapies. Medical management is based on a stepwise approach, with treatments used sequentially and escalating to either newer therapies or higher doses as patients fail to respond to each step of treatment. Most drugs have important adverse effects that may have short-term or long-term consequences.2,11 Surgery, including total colectomy and ileostomy, may be considered for patients with serious complications or for those who do not respond to medical management.3
Drug
Vedolizumab is a gut-selective anti-inflammatory biologic. It is a humanized immunoglobin G1 monoclonal antibody that binds exclusively to alpha 4 beta 7 integrin on pathogenic gut-homing lymphocytes and selectively inhibits adhesion of these cells to MAdCAM-1, which is primarily localized to blood vessels within intestinal muscosa and gut-associated lymphoid tissue. Vedolizumab has no known systemic immunosuppressive effects. Vedolizumab is available as powder for solution for IV infusion, 300 mg per vial, or solution for SC injection, 108 mg/0.68 mL pre-filled syringe or pen.6 Vedolizumab SC has been approved by Health Canada for the treatment of adult patients with CD and received a Notice of Compliance on November 19, 2020.
Vedolizumab has been approved by Health Canada for the use in:
Treatment of adult patients with moderately to severely active CD who have had an inadequate response, lost response, or were intolerant to immunomodulators or a TNF alpha antagonist; or have had an inadequate response or intolerance to, or demonstrated dependence on, corticosteroids
Treatment of adult patients with moderately to severely active UC who have had an inadequate response, loss of response, or were intolerant to either conventional therapy or infliximab, a TNF alpha antagonist.
6
The dosing of vedolizumab IV recommended by Health Canada for CD is 300 mg at 0, 2, and 6 weeks, and then every 8 weeks thereafter. When vedolizumab SC is used as a maintenance treatment following at least 2 IV infusions, the recommended dosing regimen is 108 mg administered by SC injection every 2 weeks The first SC dose should be administered in place of the next scheduled IV dose and every 2 weeks thereafter. During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice guidelines.6 Vedolizumab IV has been previously reviewed by CADTH, and received CDEC recommendations to reimburse with criteria and conditions for UC in October 2015 and for CD in October 2016. CDEC issued a recommendation to reimburse vedolizumab SC with criteria and conditions for UC in May 2020.
In the current review, the sponsor is seeking reimbursement as per the indication for vedolizumab SC, which is for the maintenance treatment of adults with moderately to severely active CD, following response to induction with vedolizumab IV.
Key Characteristics of Vedolizumab, Infliximab, Adalimumab, and Ustekinumab.
