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Minerva Gastroenterology 2021 Jul 26

DOI: 10.23736/S2724-5985.21.02985-5


language: English

Beyond biologics: advanced therapies in inflammatory bowel diseases

Giacomo CAIO 1, 2, 3, 4, Lisa LUNGARO 1, 5, Giuseppe CHIARIONI 6, 7, Fiorella GIANCOLA 1, Fabio CAPUTO 1, 3, 4, 5, Matteo GUARINO 1, Umberto VOLTA 8, Gianni TESTINO 9, 10, Rinaldo PELLICANO 11, Giorgio ZOLI 1, 3, 4, 5, Roberto DE GIORGIO 1, 3, 4

1 Department of Translational Medicine, University of Ferrara, Ferrara, Italy; 2 Mucosal Immunology and Biology Research Center, Massachusetts General Hospital-Harvard Medical School, Boston, MA, USA; 3 Center for the Study and Treatment of Chronic Inflammatory Intestinal Diseases (IBD) and Gastroenterological Manifestations of Rare Diseases, Department of Translational Medicine, University of Ferrara, Ferrara, Italy; 4 Center for the Study and Treatment of Alcohol-Related Diseases, Department of Translational Medicine, University of Ferrara, Ferrara, Italy; 5 Department of Internal Medicine, Santissima Annunziata Hospital, University of Ferrara, Cento, Ferrara, Italy; 6 Division of Gastroenterology of the University of Verona, A.O.U.I. Verona, Verona, Italy; 7 Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 8 Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; 9 Unit of Addiction and epatology/Alcohological Regional Centre, ASL3 c/o IRCCS San Martino Hospital, Genova, Italy; 10 Italian Society on Alcohol, Bologna, Italy; 11 Unit of Gastroenterology, Molinette Hospital, Turin, Italy


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.

KEY WORDS: Crohn’s Disease; Ulcerative Colitis; Small molecules; Janus Kinases Inhibitors; SP1 agonists

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