Background and Significance: In the United States, Crohn’s disease (CD) and ulcerative colitis (UC), collectively referred to as inflammatory bowel disease (IBD), affect approximately 1.2 million individuals, cost over $6 billion annually, and cause substantial patient morbidity, missed work and school, and diminished quality of life. Currently, anti-TNF therapy is considered first-line treatment for moderate to severe disease. Yet, up to 80 percent of patients do not respond or ultimately lose response to anti-TNF. As the treatment armamentarium continues to grow, patients now have additional options to choose from. For patients with CD, these newer treatments include vedolizumab and ustekinumab. For UC, new treatment options include vedolizumab or tofacitinib, a small-molecule JAK inhibitor that is anticipated to be approved by the Food and Drug Administration to treat UC in March 2018. Unfortunately, anti-TNF-refractory patients are often refractory to these newer treatments as well. Hence, selecting the most effective option is of paramount importance. Yet, there are no head-to-head studies to compare these options and help guide this common and important treatment decision.
For this reason, the Institute of Medicine, the Crohn’s & Colitis Foundation (the Foundation), and others have prioritized comparative effectiveness research that helps patients and their providers make more-informed health choices. The overarching aim of this project is to compare the effectiveness of non-anti-TNF biologics and small molecules in patients who are refractory to anti-TNF therapy. To address this pressing need as quickly and efficiently as possible, we will leverage the research infrastructure that has been recently developed by PCORnet, the National Patient-Centered Clinical Research Network, and by IBD Plexus, the Foundation’s new research exchange platform designed to accelerate IBD research facilitate collaboration between stakeholders. Through the use of these varied sources of real-world data, our study findings will be broadly generalizable and directly inform these important patient treatment decisions.
Study Aim 1: To compare the effectiveness of second-line biologic agents (ustekinumab versus vedolizumab) among patients with CD who are anti-TNF primary or secondary nonresponders.
Study Aim 2: To compare the effectiveness of a second-line biologic agent (vedolizumab) versus a small molecule (tofacitinib) among patients with UC who are anti-TNF primary or secondary nonresponders.
Study Description: Each aim will be addressed by two approaches. First, we will recruit 180 patients with each condition who are starting one of the treatments we are comparing. Participants will come from approximately 18 study centers across the country. Participants may also be referred by our partner health plans, Anthem Blue Cross Blue Shield and Humana, or join the study directly through our patient-powered research network (www.ccfapartners.org). The study will focus on patient-reported outcomes, including pain, fatigue, and other symptoms, that will be collected through electronic surveys. The second approach will leverage real-world data collected by our health plan partners, including claims for office visits, hospital visits, medications, and other healthcare encounters.
We will use these data to compare these treatment approaches, focusing on outcomes such as length of time patients remain on treatment and the ability to prevent hospitalization and surgery. We will engage patients and other stakeholders at each phase of the study from conception and planning through analysis and dissemination. This will ensure that the results of this project provide patients and their physicians strong evidence that will directly inform this important treatment decision. Completion of these aims will not only answer two high-priority patient-centered comparative effectiveness research questions, but will also leverage the existing research infrastructure of PCORnet and the Crohn’s & Colitis Foundation and forge multistakeholder partnerships contributing to the sustainability of both organizations.
*All proposed projects, including requested budgets and project periods, are approved subject to a programmatic and budget review by PCORI staff and the negotiation of a formal award contract.