Association Between Obesity and Response to Biologic Therapy in Inflammatory Bowel Diseases

Association Between Obesity and Response to Biologic Therapy in Inflammatory Bowel Diseases

ACG Junior Faculty Development Award 2016, to Singh
CCFA Career Development Award 2016, to Singh
I will be applying for funding for the AGA-Pfizer Pilot Award for Inflammatory Bowel Diseases 2017, for this proposal

Ad-hoc consultation on GuidePoint LLC, Research Grant from Pfizer, Dr. Sandborn receives consulting fees from Kyowa Hakko Kirin, Millennium, Celgene, Prometheus, Santarus, AbbVie, Catabasis, Vertex, Warner Chilcott, Gilead Sciences, Cosmo Pharmaceuticals, Ferring, Sigmoid Pharma, Tillotts Pharma, and Am Pharma.

Over a third of adults in the United States are obese. Fat releases toxins that can cause several diseases like diabetes and heart disease. Inflammatory bowel diseases are lifelong autoimmune diseases, affecting over 1.6 million Americans, across all ages, and significantly impact quality of life, resulting in frequent hospitalizations, surgeries, need for steroids and expensive immunosuppressive medications. Obese patients are at higher risk of developing IBD, and obese IBD patients may have a more severe disease course. It is unclear how obesity modifies response to treatment in IBD. We will evaluate the association between obesity and response to biologic therapy, through analyses of late stage (Phase III), placebo-controlled trials of vedolizumab and certolizumab pegol in IBD. The information generated through this study would be invaluable to inform both science and patient care. From a scientific perspective, it will advance understanding of IBD pathophysiology, offering potential clues into role of mesenteric fat, adipocytokines and gastrointestinal hormones in IBD pathogenesis as well as pharmacokinetics of biologic therapy. From a clinical perspective, information generated from this study on treatment response to biologic therapy, will be generalizable and directly applicable to patient care offering potential for personalized therapy based on body habitus, while simultaneously enhancing design of future clinical trials. It may enable an innovative therapeutic approach to IBD management by targeting obesity through lifestyle modification, pharmacological and/or endoscopic weight loss procedures, to modify IBD outcomes.

For this study, we'll include patients receiving vedolizumab or certolizumab pegol in phase III trials of moderate-severe IBD. We'll analyze differences in rates of clinical remission and biochemical remission, by baseline body mass index at time of enrollment (low <18.5kg/m2, normal 18.5-25.0kg/m2, overweight, 25.1-29.9kg/m2, class I obesity, 30.0-34.9kg/m2 and class II/III obesity, =35.0kg/m2). Patients with ulcerative colitis and Crohn's disease will be analyzed separately, and all analyses will be adjusted for factors that modify pharmacokinetics of biologics agents (sex, concomitant immunomodulator therapy, baseline C-reactive protein, albumin), confounding variables (like baseline disease activity, concomitant prednisone use) and serum drug level.

Findings from these studies will be presented at leading gastroenterology meetings, and disseminated in scientific media through research publications. They'll be communicated to patients and public, through partnership with the Crohn's and Colitis Foundation of America, the leading patient-physician organization for IBD.

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Medicine: Certolizumab Pegol , Condition: Crohn's Disease, Phase: 3, Clinical Study ID: C87031, Sponsor: UCB" },{ "PostingID": 2361, "Title": "UCB-C87032", "Description": "Study to Test the Effect of CDP870 in the Treatment of Crohn's Disease Over 26 Weeks, Comparing CDP870 to a Dummy Drug (Placebo), Following 3 Doses of Active Drug (CDP870).

Medicine: Certolizumab Pegol , Condition: Crohn's Disease, Phase: 3, Clinical Study ID: C87032, Sponsor: UCB" },{ "PostingID": 3918, "Title": "UCB-C87085", "Description": "Study to Evaluate Efficacy and Safety of Certolizumab Pegol for Induction of Remission in Patients With Crohn's Disease

Medicine: Certolizumab Pegol , Condition: Crohn's Disease, Phase: 3, Clinical Study ID: C87085, Sponsor: UCB" }]

The publication citation will be added after the research is published.