The Expanding Role of Anti-IL-12 and/or Anti-IL-23 Antibodies in the Treatment of Inflammatory Bowel Disease.

The interleukin (IL)-12/IL-23 pathway is one of many proposed mechanistic pathways of intestinal inflammation. Earlier studies introduced IL-12 as a major cytokine in the pathogenesis of inflammatory bowel disease. However, the discovery of IL-23 drew attention toward this new cytokine. Overwhelming data indicated that antibodies against IL-12p40 rendered their anti-inflammatory effect primarily via inhibition of IL-23. This is because IL-12 and IL-23 have the subunit p40 in common. These cytokines have become an attractive target of treatment in patients with inflammatory bowel disease. Targeting IL-12 selectively was not found to be an efficacious treatment. Coblockade of IL-12 and IL-23 via targeting of p40, however, was found to be effective. More recently, selective IL-23 blockade has been extensively studied with promising preliminary results. To date, there are several ongoing randomized clinical trials investigating the safety and efficacy profiles of selective IL-23 inhibitors. Overall, the classes of anti-IL-12/IL-23 inhibitors and selective IL-23 inhibitors seem to be effective alternatives in patients who are nonresponders to anti-tumor necrosis factor-α agents, especially in a subgroup of secondary nonresponders. In addition, the immunogenicity and adverse event rates associated with antibodies against IL-12 and/or IL-23 seem to be very low. Considering all of this, these agents will be an important part of the treatment algorithm for patients with inflammatory bowel disease going forward.