Ulcerative colitis: shedding light on emerging agents and strategies in preclinical and early clinical development

Ulcerative colitis (UC) is an inflammatory disease of the large intestine. Progress in preclinical therapeutic target discovery and clinical trial design has resulted in the approval of new therapies. Nonetheless, remission rates remain below 30% thus underlining the need for novel, more effective therapies.This paper reviews current experimental techniques available for drug testing in intestinal inflammation and examines new therapies in clinical development for the treatment of UC. The authors searched the literature for 'ulcerative colitis' AND 'preclinical' OR 'drug target/drug name' (i.e. infliximab, vedolizumab, IL-12, IL-23, JAK, etc.). Studies that included preclinical in vivo or in vitro experiments are discussed. The clinicaltrial.gov site was searched for 'ulcerative colitis' AND 'Recruiting' OR 'Active, not recruiting' AND 'Interventional (Clinical Trial)' AND 'early phase 1' OR 'phase 1' OR 'phase 2' OR 'phase 3.'Using in vivo, ex vivo, and/or in vitro models could increase the success rates of drugs moving to clinical trials, and hence increase the efficiency of this costly process. Selective JAK1 inhibitors, S1P modulators, and anti-p19 antibodies are the most promising options to improve treatment effectiveness. The development of drugs with gut-restricted exposure may provide increased efficacy and an improved safety.