Beyond biologics: advanced therapies in inflammatory bowel diseases

Inflammatory bowel diseases (IBDs) are conditions characterized by persistent and relapsing inflammation involving the gastrointestinal tract at various levels. Although the etiopathogenesis of IBDs is partially understood, a deregulated activation of intestinal immune cells in genetically susceptible patients is thought to be key for the disease onset and evolution. Artificial Nutrition might affect favorably on inflammation and related cytokine storm. However, the discovery of monoclonal antibodies blocking pro-inflammatory cytokines (e.g., tumor necrosis factor-α - TNF-α) changed radically the management of IBDs. Anti-TNF-α agents represent the prototype molecule of the so-called 'biologics' / 'biologicals'. These compounds have significantly improved the therapeutic management of IBDs refractory to standard medications, achieving clinical remission, mucosal healing and preventing extra-intestinal manifestations. However, about 50% of patients treated with biologicals experienced drawbacks, such as primary failure or loss of response, requiring new effective treatments. Translational studies have identified other pathways, different from the TNF-α blockade, and new molecules, e.g. sphingosine-1-phosphate agonists and the JAK kinase inhibitors, have been proposed as potential therapeutic options for IBDs. These novel therapeutic approaches represent a "new era" of IBD management, especially for patients poorly responsive to biologicals. In this review, we will summarize the new pharmacological strategies to treat IBDs, and discuss their effectiveness and safety, along with future perspectives for IBD treatment.