Patient Group Input
This section was prepared by CADTH staff based on the input provided by patient groups.
About the Patient Groups and Information Gathered
Two patient groups submitted input for this review: the Gastrointestinal Society (GI Society) and Crohn’s and Colitis Canada (CCC).
The GI Society is a national registered charity that is committed to improving the lives of patients with GI and liver conditions by supporting research, advocating for patient access to health care, and promoting overall GI and liver health. The GI Society delivers information through the BadGut Basics pamphlets and a newsletter called Inside Tract | Du coeur au ventre. Furthermore, the GI Society informs Canadians through free BadGut lectures given coast to coast, covering various digestive conditions for patients, caregivers and others, and manages a website in both English and French. The society provides additional patient resources, such as responding to information requests and participating in community initiatives. The society has also supported several GI research studies along with its sister charity, the Canadian Society of Intestinal Research.
As a national, volunteer-based charity focused on finding the cures for CD and UC and improving the lives of people affected by these diseases, CCC has a network of volunteer-led chapters in 46 communities across the country, offering information, events, fundraising opportunities, and encouragement. Since its founding in 1974, CCC has invested more than $130 million in CD and colitis research. In addition, the organization provides patient programs, advocacy, and awareness.
None of the patient groups received help from outside their organizations to complete the submissions, or to collect or analyze data used in their submissions. Takeda Inc., the sponsor of Entyvio, provided funding to the GI Society in excess of $50,000 in 2019. Financial payments of more than $50,000 from different pharmaceutical companies, including Takeda, were reported by CCC over the past 2 years.
For the GI Society, patient input used to inform this submission was obtained through 3 surveys: a 2015 survey completed by 423 Canadians with IBD including CD; a 2018 survey completed by 432 Canadians with IBD, 56% of whom had CD; and an ongoing survey, which has had approximately 500 respondents. The GI Society has also had direct contact with patients affected with IBD at BadGut Lectures, patient roundtables, and through telephone calls, emails, and social media.
CCC gathered patient perspectives via its published reports, such as the 2018 Impact of Inflammatory Bowel Disease (IBD) Report, and informational brochures found on CCC’s website. A series of surveys conducted in June 2020 and interviews with 21 patients who had experience with vedolizumab in treating CD contributed to this submission as well.
Disease Experience
The patient groups described CD as a chronic GI condition that primarily affects the small intestine and/or colon. The most frequent symptoms associated with CD are persistent diarrhea, rectal bleeding, abdominal pain, and weight loss. These symptoms vary from person to person and may change over time. Patients with CD may also experience symptoms outside of the GI tract that may affect the joints, bones, eyes, skin, and liver. Fever and fatigue are common. Anemia may also present when diarrhea and blood loss are severe. Development of fistula, most commonly around the anal area, is another serious complication of CD. In addition to the physical symptoms, the patient groups stated that CD has a profound effect on patients’ emotional and social life. It can affect a person’s sense of self, particularly for children and young adults. Both patient groups indicated that patients are constantly concerned with future flare-ups, which can be unpredictable and severely disruptive.
Responses to GI Society surveys included: “It’s like I can’t control anything. I feel weak and can barely get up. My biggest concerns usually when I see blood and determining at what point to go to the ER” and “The worst part is fear of irreversible permanent damage that will affect your day to day life forever.”
Respondents in the CCC survey indicated that pain and frequent unpredictable bowel movements were their top priority concerns. They experienced “a constant urgency to use the bathroom and the malabsorption (of nutrients) that comes from the frequent bowel movements,” “horrible cramping,” and “the need to wear an adult diaper to bed at night.”
Experience With Treatment
The GI Society described treatment of CD as multifaceted as it involves managing symptoms and consequences of the disease, as well as trying to reduce the underlying inflammation. When one medication fails to treat their disease, patients switch to another type. First-line treatments for CD include anti-inflammatory drugs such as 5-aminosalicylic acid and corticosteroids to control disease flare-ups. These drugs can settle acute inflammation and for some, can keep inflammation inactive when taken long-term (maintenance). Corticosteroids in rectal formulations may be used for topical relief; however, these can be ineffective for a patient with significant diarrhea. Immunosuppressants help reduce dependence on steroids and can be used in patients with steroid-resistant disease, although it could take 6 months to see any results. When other medications fail to relieve symptoms, biologics are used. Even though different treatment options are available, many patients still have difficulties obtaining remission and/or adequate symptom relief. For example, in the GI Society submission, 63% of respondents (many of whom had been suffering for years) reported symptom reduction on a biologic and 23% reported confirmed remission. One male patient had experience with Humira and vedolizumab. After losing efficacy with Humira (the patient failed to take Humira consistently when he was feeling well), he received vedolizumab through a clinical trial. The patient noted that his diarrhea was manageable with vedolizumab and the associated pain decreased, although he still experienced some urgency. He also liked the delivery method (SC injection) of vedolizumab. This patient rated his experience with vedolizumab 10 out of 10 in an assessment.
Many respondents from the CCC group have experienced multiple medications over many years. One patient said, “I have tried over 20 different treatments since 1998.” Patients reported various side effects associated with the current treatment options, such as kidney damage, skin reactions, or liver damage. In some cases, the side effects led to the discontinuation of treatment. Some patients required invasive surgery due to ineffective treatments as the disease progressed. Among the 21 patients who had experience with vedolizumab, benefits of this treatment were reported. The most commonly reported side effect associated with vedolizumab was fatigue.
The following quotes provide patient perspectives associated with this treatment.
“… keep me in remission which allowed me to enjoy more events socially.”
“My Crohn’s has been under control since I’ve been under Entyvio without too many side effects.”
“I definitely feel that my symptoms are much better on Entyvio. With that being said I’m not symptom free but I am able to manage life very well … have enough energy/good health days to complete everything that comes up in my life.”
The CCC patient group also described the challenge related to the time commitment required for treatment.
Improved Outcomes
Both patient groups emphasized the importance of symptom relief, quality-of-life improvements, and achieving remission in patients with CD.
The GI Society indicated that given that all patients respond differently to treatment, it is important for them to have access to a variety of treatment options. The patient group suggested that vedolizumab has the potential to improve the health and quality of life of many individuals currently suffering from ineffective treatments.
Patients responding through CCC expressed concerns about the challenges in receiving medication for CD via infusion at clinics due to the significant time commitment and time away from work and school. In addition, for patients who are at high risk for coronavirus disease 2019, those who have comorbid conditions, or those experiencing challenges with infusions due to difficulties finding an appropriate IV injection site, a self-administered option, such as the SC formulation of vedolizumab, is desirable.
Clinician Input
All CADTH review teams include at least one clinical specialist with expertise in the diagnosis and management of the condition for which the drug is indicated. Clinical experts are a critical part of the review team and are involved in all phases of the review process (e.g., providing guidance on the development of the review protocol; assisting in the critical appraisal of clinical evidence; interpreting the clinical relevance of the results; and providing guidance on the potential place in therapy). The following input was provided by one clinical specialist with expertise in the diagnosis and management of CD.
Based on current standards of practice with existing therapies, the clinical expert consulted by CADTH indicated that there are several areas of unmet need where vedolizumab SC may play a role:
as primary induction therapy for CD in patients who are primarily non-responsive to either conventional therapy with immunomodulators or TNF alpha antagonists
in the setting of secondary non-response during maintenance therapy; an important proportion of CD patients will lose response to TNF alpha antagonist therapy during maintenance, either due to formation of anti-drug antibodies or to inflammatory mechanisms that are independent of TNF
as salvage therapy for patients responding to immunomodulation therapy or TNF alpha antagonists who develop adverse effects to therapy; while immunomodulators such as azathioprine and methotrexate are generally safe medications, well-known side effects include the development of pancreatitis, neutropenia, hepatitis, and neoplasia (e.g., skin cancers); in addition, severe allergic reactions, psoriatic skin diseases, neurological complications, congestive heart failure, lupus, and severe infections can be associated with TNF alpha antagonists.
Patients with moderate to severe CD require treatment with biologic therapies (typically starting with the TNF alpha antagonists infliximab and adalimumab) after not meeting treatment goals with aminosalicylates, immunosuppressants, and corticosteroids. Biologic treatments are usually administered in combination with an immunosuppressant such as azathioprine or methotrexate. Patients who respond to this approach may continue with biologic treatment for several years. However, some patients experience a reduction in response over time (e.g., due to the development of antibodies to a particular biologic treatment) or become intolerant of biologic treatment (e.g., due to side effects such as an allergic reaction or other drug-related complications), which necessitates a change in the treatment regimen in order to maintain clinical responsiveness. At present, patients who experience a loss of response to either infliximab or adalimumab can be switched to the other TNF alpha antagonist, although this is often associated with a lower clinical response compared with that in patients who have not been exposed previously to a TNF alpha antagonist. Therefore, there exists an unmet need for patients with moderate to severe CD who are no longer responsive to or intolerant of TNF alpha antagonists.
Vedolizumab is a biologic agent that is an integrin inhibitor, and therefore represents a different class of biologic compared to the TNF alpha antagonists and the IL-12 and IL-23 inhibitor ustekinumab.
There are no barriers to identifying patients for whom vedolizumab treatment would be appropriate in a consistent manner, although a specialized diagnostic test, such as endoscopy, computed tomography scan, abdominal ultrasound, or magnetic resonance enterography, is usually required to assess disease activity and severity for all patients who require biologic therapy, in accordance with standard clinical practice. The following are also advisable to assess prior to initiating treatment:
assessment for previous TB exposure
hepatitis B serology
pregnancy test in women of childbearing age
immunization history and boosters for low antibody titers.
