Novel Pharmacological Therapy in Inflammatory Bowel Diseases: Beyond Anti-Tumor Necrosis Factor

Abstract

Inflammatory bowel diseases (IBDs) are chronic conditions of the gastrointestinal tract in which dysregulated immune responses cause persistent inflammation of the gut mucosa. Biologic therapy with anti-TNF blockers has revolutionized the therapeutic management of IBD for their remarkable efficacy and potential impact on disease course and for many years has represented the sole treatment option for patients refractory or intolerant to conventional therapy. In recent years, more molecules, both biologically and chemically synthetized, have been developed as potential therapeutic options for IBD that target different molecular pathways aside from TNF blockade, and which have been proposed as targets for novel drugs. This is particularly relevant for the present, as well as future, management of IBD, considering that some patients are refractory to anti-TNF. This review will summarize the pharmacological options, either currently available or in the pipeline, for market approval to treat IBD, besides anti-TNF strategies, based on their mechanism(s) of action. We will also analyze the current evidence for effectiveness and safety, as well as offer perspective, regarding the potential implementation for such therapies in the future.

Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

“…Indeed, as many types of intestinal cells produce a wide range of effector cytokines, it is not surprising that it may be necessary to simultaneously target multiple cytokines to effectively suppress intestinal pathology. This is supported by positive effects of concomitant blockade of IL-12 and IL-23 using a monoclonal antibody against the IL-12p40 subunit (11,330,331,(333)(334)(335)(336)(337)(338)(339).…”

Anti-Inflammatory and Chemopreventive Effects of Bryophyllum pinnatum (Lamarck) Leaf Extract in Experimental Colitis Models in Rodents

“…Recurrence is common, along with severe complications and poor prognosis by pharmacological treatment (Wu et al, 2020). The pharmacological treatments for human IBD mainly comprise anti-inflammatory and immunosuppressive drugs, which can be linked to significant side effects, thus limiting their use (Pagnini et al, 2019). There is consequently a clear demand for new treatments which combine efficacy and safety, such as those of natural origin.…”

Aminoacyl-tRNA synthetase inhibition activates a pathway that branches from the canonical amino acid response in mammalian cells

“…HF further suppresses key proinflammatory responses, in IL-23-stimulated T H 17 memory cells and IL-1β-stimulated FLS, also in cells that lack GCN2. These findings make HF, and its chemical derivatives, attractive drug candidates for disease settings in which anti-TNF biologics have been successful, such as RA and Crohn's disease (132,133). Small-molecule inhibitors of TNF-α tissue programs could be much needed adjuncts, or alternatives to biologic therapies in instances of immunogenicity (133), while providing added tissue benefit via inhibition of both T H 17-driven inflammation and TGF-β-stimulated fibrosis.…”