Targeting the il-12/23 pathway for inflammatory bowel disease: Current concepts and future directions

Medical therapy for inflammatory bowel disease (IBD), which includes both Crohn’s disease (CD) and ulcerative colitis (UC), has rapidly evolved in the last twenty years. Anti-tumor necrosis factor (TNF) therapy was the first of the biologic agents on the market. Up to one-half of patients either will fail to respond to anti-TNF agents or will eventually lose response. Newer biologic agents targeting the IL-12/23 pathway are effective in treating IBD, even among patients who have previously failed other mechanisms including anti-TNF therapy and steroids. Ustekinumab is first in class for IBD. With a favorable safety profile and excellent efficacy, first line use of this agent in patients with IBD is appropriate. Nevertheless, as the newest category of biologic on the IBD market, this class remains somewhat unfamiliar to many clinicians and patients. This review aims to answer common questions regarding IL-12/23 drug mechanism, safety, efficacy, clinical application, and therapeutic pipeline.