Novel Pharmaceuticals and Therapeutics for Tumor Necrosis Factor-Alpha-Resistant Crohn's Disease: A Narrative Review

Inflammatory bowel disease (IBD) is a medical condition that causes persistent, relapsing inflammation of the gastrointestinal tract. It is an umbrella term encompassing two different conditions: ulcerative colitis (UC) and Crohn's disease (CD). The standard treatment for patients with moderate to severe CD is tumor necrosis factor-alpha (TNF-alpha) inhibitors; however, a subset of CD patients face challenges in regard to this disease's treatment. Certain populations of patients with CD may exhibit resistance or develop tolerance to TNF-alpha inhibitor therapy over time. The recurrent gastrointestinal inflammation associated with CD can severely impact the quality of life and lead to complications for those suffering from this condition. The symptomatic flare-ups these subpopulations continue to experience underscores why such a need for alternative therapies is desperately needed. These alternative therapies not only offer potential benefits for those with TNF-alpha resistance, but CD may also serve as a superior therapy option for those trying to avoid the adverse effects of CD treatments available today. This review aims to explore and investigate the novel drugs and therapies that are being investigated for the treatment of TNF-alpha resistant CD, such as upadacitinib, risankizumab, vedolizumab, synbiotics, fecal microbiota transplantation (FMT), and stem cell therapy. Upadacitinib is a Janus kinase inhibitor, Risankizumab is a monoclonal antibody targeting interleukin-23, and Vedolizumab is an integrin receptor antagonist. The latest advancements in CD management have shown encouraging results. Some of these novel drugs and therapies not only offer a potential solution for CD patients exhibiting resistance to TNF-alpha inhibitors but may also provide a superior alternative for individuals prone to opportunistic infections.