title: When combination therapy isn't working: emerging therapies for the management of inflammatory bowel disease.
abstract: Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.
authors.affiliation: Suneeta Krishnareddy, Arun Swaminath, Mount Sinai School of Medicine, Columbia University Medical Center, New York, NY 10029, United States.
authors.forename: Suneeta
authors.initials: S
authors.lastname: Krishnareddy
authors.affiliation: Suneeta Krishnareddy, Arun Swaminath, Mount Sinai School of Medicine, Columbia University Medical Center, New York, NY 10029, United States.
authors.forename: Arun
authors.initials: A
authors.lastname: Swaminath
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use*; D015195:Drug Design; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005765:Gastrointestinal Agents / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000276:immunology; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects; D017211:Treatment Failure
chemical_list: D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents
keywords: Emerging therapies; Inflammatory bowel disease; Tofacitinib; Ustekinumab; Vedolizumab