Impact of Obesity on Response to Biologic Therapies in Patients with Inflammatory Bowel Diseases

Approximately 20-40% of patients with inflammatory bowel disease (IBD) are obese. Obesity is associated with inferior outcomes in patients with IBD, with lower rates of achieving remission, poor quality of life, and higher burden of unplanned healthcare utilization. Multiple cohort studies in patients with immune-mediated inflammatory diseases, including IBD, treated with biologic agents like tumor necrosis factor-α antagonists have suggested that obesity is associated with inferior response to biologic therapy. This may be related to the negative impact of obesity on the pharmacokinetics of biologic agents. Pharmacokinetic studies of multiple biologic agents have demonstrated that high body weight is associated with more rapid clearance and a higher volume of distribution of biologic agents, which leads to low trough concentrations. Randomized trials in patients with psoriasis and psoriatic arthritis treated with biologic agents suggest that diet- or lifestyle-induced weight loss is associated with improved response to therapy. This provides an opportunity to explore intentional weight loss as adjunctive therapy in obese patients with IBD. However, diet and lifestyle interventions for weight loss are hard to implement in patients with IBD; hence, long-term therapy with weight-loss agents (such as with phentermine-topiramate, naltrexone-bupropion) is attractive as adjunctive therapy in obese patients with IBD.