Quantitative pharmacology assessment strategy therapeutic proteins in pediatric subjects - challenges and opportunities

Therapeutic proteins (TPs) are critical in the treatment of a variety of diseases in the pediatric population. This chapter covers issues related to studying TPs in the pediatric population, including extrapolation of efficacy, timing, and initiation of pediatric trials, informative priors, and trial design considerations, using inflammatory bowel disease (IBD) as a representative example. There are two tumor necrosis factor -a blockers approved in children for IBD, infliximab for Crohn’s disease and ulcerative colitis while adalimumab is approved for CD. Exposure-response analysis played an important role in approval of infliximab for UC and adalimumab for CD. This chapter summarizes these two case studies. It briefly highlights two advanced modeling approaches, namely quantitative systems pharmacology and clinical trial simulation, and describes how they can be leveraged in advancing important novel therapeutics for the benefit of patients with inflammatory diseases like IBD, where population size is small.