Purpose of Review
Inflammatory bowel disease (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), is an unmet need as indicated by less than ideal remission rates with current treatments. Understanding the clinical development of approved IBD biological therapy, particularly dose selection, may help improve future biologic development.
Recent Findings
Seven biologics have been approved for CD and/or UC in the last two decades (as of January 2019), including anti-tumor necrosis factors (anti-TNFs) (infliximab, adalimumab, certolizumab, and golimumab), anti-integrins (natalizumab and vedolizumab), and anti-interleukin (IL)-12/IL-23 (ustekinumab). These agents demonstrate effectiveness in inducing sustained clinical remission despite the high and variable “placebo” response. Side effects such as infections and malignancies can occur for biologics partly due to the long-term immunosuppression. IBD biologics typically employ an intensive induction followed by maintenance therapy. Approved dose regimen (especially induction) tends to be the same or close to the highest doses that have been evaluated in clinical development, indicating a limited dose range tested. Biologics approved for CD and UC use the same dose regimen though a given drug may not work equally effectively for both indications.
Summary
Lessons learned from current IBD biological therapy may help enhance the clinical development efficiency of future biologics, e.g., test a wide dose range; characterize full dose-response for desirable and untoward effects; understand influencing factors to the treatment (and placebo) effect; and leverage dose-ranging learning between CD and UC.