Gut-directed therapeutics in inflammatory bowel disease

Purpose of review

Tissue-directed therapies (TDTs) provide potential advantages, including improved tolerance, safety, and efficacy. This review provides a conceptual framework for understanding intestinal TDT and summarizes the current landscape of TDT in inflammatory bowel disease (IBD).

Recent findings

Vedolizumab, a mAb targeting the gut homing a4b7 integrin, served as revolutionary proof-of-principle for the power of advanced TDT in IBD. The development of other monoclonal antibodies targeting cell adhesion molecules followed including abrilumab (a4b7), etrolizumab (b7), and ontamalimab (MAdCAM1). MORF-057, an oral small molecule inhibitor of a4b7, is now in development for ulcerative colitis.Efforts have also been made toward gut specific JAK inhibitors. Microbiome-based therapies, including engineered probiotics, bacteriophages, and postbiotics, are gaining interest. There are also a number of innovative drug delivery methods, including engineered yeast, hydrogels, and nanoparticles, and viralbased gene therapy

Summary

Gut-targeted therapies range from novel variations on traditional drugs (i.e., mAbs and small molecules) to microbiome-based therapeutics and engineered delivery systems. They can be used alone or incombination with currently available therapies. Future directions should focus on the development of triedandtrue modalities (mAbs, small molecules) as well as the microbiome and more innovative deliverysystems.