J Gastrointestin Liver Dis, June 2015 Vol. 24 No 2: 203-213 Department of Gastroenterology, Oncology- Surgery, L.Sacco University Hospital Via GB Grassi, Milan, Italy Address for correspondence: Giovanni Maconi Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Via GB Grassi, Milan 20157, Italy giovanni.maconi@unimi.it Received: 05.02.2015 Accepted: 25.03.2015 Overview of Biological Terapy in Ulcerative Colitis: Current and Future Directions Federica Furfaro, Cristina Bezzio, Sandro Ardizzone, Alessandro Massari, Roberto de Franchis, Giovanni Maconi INTRODUCTION Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by the alternation of acute and remission phases, affecting mainly young patients, whose quality of life may be strongly compromised by the disease progression. In fact, over time, the progression of UC may lead to an impairment of the normal anatomy and physiology of the colon due to proximal extension, stricturing, dysmotility and REVIEW ABSTRACT Te treatment of ulcerative colitis (UC) has changed over the last decade. It is extremely important to optimize the therapies which are available nowadays and commonly used in daily clinical practice, as well as to stimulate the search for more powerful drugs for the induction and maintenance of sustained and durable remission, thus preventing further complications. Terefore, it is mandatory to identify the patients’ prognostic variables associated with an aggressive clinical course and to test the most potent therapies accordingly. To date, the conventional therapeutic approach based on corticosteroids, salicylates (sulfasalazine, 5-aminosalicylic acid) or immunosuppressive agents is commonly used as a frst step to induce and to maintain remission. However, in recent years, knowledge of new pathogenetic mechanisms of ulcerative colitis have allowed us to fnd new therapeutic targets leading to the development of new treatments that directly target proinfammatory mediators, such as TNF-alpha, cytokines, membrane migration agents, cellular therapies. Te aim of this review is to provide the most signifcant data regarding the therapeutic role of drugs in UC and to give an overview of biological and experimental drugs that will become available in the near future. In particular, we will analyse the role of these drugs in the treatment of acute fare and maintenance of UC, as well as its importance in mucosal healing and in treating patients at a high risk of relapse. Key words: ulcerative colitis – therapy – biological therapy – infiximab – adalimumab. Abbreviations: ADA: adalimumab; AZA: azathioprine; CyA: cyclosporine; EMA: European Medicines Agency; FDA: Food and Drug Administration; IBD: infammatory bowel disease; IBDQ: infammatory bowel disease questionnaire; IFX: infiximab; PGA: physician‘s global assessment; TNF-α: tumour necrosis factor alpha; UC: ulcerative colitis. Available from: URL: http://www.jgld.ro/2015/2/16.html DOI: http://dx.doi.org/ 10.15403/jgld.2014.1121.242.bezz anorectal dysfunction (tenesmus, urgency, incontinence) [1]. All these aspects, together with the occurrence of extraintestinal manifestations and incidence of dysplasia and colorectal cancer, can impact on the working and overall ability of patients and ultimately on their quality of life [2, 3]. It should also be taken into consideration that only half of the patients with UC show a stable remission over time, whilst the remainder may have a more aggressive clinical course characterized by frequent relapses, severe onset of disease, refractoriness and steroid-dependency [4, 5]. Moreover, even in patients in clinical remission, the persistence of mucosal lesions may have a relevant negative impact on the clinical course of disease, with a signifcantly increased immunosuppression, hospitalization and colectomy rates [6]. Te conventional approach to managing active UC is aimed at obtaining clinical response and at inducing and maintaining clinical and endoscopic corticosteroid-free remission.