Beyond biologics: advanced therapies in inflammatory bowel diseases

INTRODUCTION: Inflammatory bowel diseases (IBDs) are conditions affecting the gut at different levels characterized by an abnormal activation of the intestinal immune system. In this narrative review, we will provide the reader with an update on the efficacy and safety of new pharmacological strategies to treat IBD patients. EVIDENCE ACQUISITION: We performed a thorough literature review via PubMed, EMBASE, MEDLINE and Sci-ence Direct databases addressing studies reporting on new therapies for IBD management published in the last ten years (January 2010-December 2020). Data from pharmaceutical companies and abstracts of conferences/meetings have also been considered. EVIDENCE SYNTHESIS: The discovery of monoclonal antibodies blocking pro-inflammatory cytokines,e.g., tumor necrosis factor-a (TNF-a) radically changed the management of IBDs. Anti-TNF-a agents represent the prototype molecule of biologics/biologicals. These compounds have significantly improved the therapeutic management of IBDs refractory to standard medications as they provide clinical remission, mucosal healing and prevent extra-intestinal manifestations. However, about 50% of patients treated with biologicals experienced drawbacks, including primary failure or loss of response, requiring new effective treatments. Translational studies have identified new strategies, different from the TNF-a blockade, and new molecules, e.g. sphingosine-1-phosphate agonists and the JAK kinase inhibitors, have been proposed as potential therapeutic options for IBDs. CONCLUSIONS: With the availability of novel approaches reviewed in this article, physicians and especially gastroen-terologists will increase the therapeutic options to provide a better management of IBD patients, particularly those poorly responsive to biologicals. (Cite this article as: Caio G, Lungaro L, Chiarioni G, Giancola F, Caputo F, Guarino M, et al. Beyond biologics: advanced therapies in inflammatory bowel diseases. Minerva Gastroenterol 2022;68:319-32. DOI: 10.23736/S2724-5985.21.02985-5)

Automated summary

This narrative review provides an update on the efficacy and safety of new pharmacological strategies for the treatment of inflammatory bowel diseases (IBDs), focusing on the discovery of monoclonal antibodies blocking pro-inflammatory cytokines and the identification of new therapeutic options beyond the TNF-α blockade. The availability of novel approaches and molecules offers additional therapeutic options for IBD patients who are poorly responsive to biologicals.