They have the potential to treat a larger quantity of patients at cost parity and to extend availability of biologics in countries where those drugs were unaffordable for few years beforehand. Besides classical pro-inflammatory role in the onset and maintenance of chronic intestinal inflammation, more SB 415286 recent studies have highlighted a possible protective role of TNF at mucosal level. to the role that TNF plays in intestinal homeostasis that is particularly important during the early phase of the inflammatory process. In fact, emerging evidence supporting the dichotomous role of TNF and the identification of molecular markers will guideline a more tailored and processed therapy for CD patients in the near future. strong class=”kwd-title” Keywords: Crohns disease, tumor necrosis factor, anti-TNF, infliximab, adalimumab, certolizumab, innate immunity 1. Introduction Crohns disease (CD) is usually a complex, chronic disorder of the intestine with still unknown etiology. It is one of the etiopathogenic forms of inflammatory bowel disease (IBD), a group of disorders wherein dysregulated mucosal immune responses causes a prolonged inflammation of the gut with a clinical relapsing-recurrent pattern of disease . Unlike ulcerative colitis (UC), the other major form of IBD, in which inflammation is limited histologically to the mucosal surface and localized to the colon, inflammation in CD affects all the intestinal wall SB 415286 layers of the GI tract. CD may involve virtually all areas of the digestive tract with the terminal ileum representing the most frequent location. The natural history of the disease is usually typically characterized by an initial phase, inflammatory phenotype, where the clinical manifestations are mainly related to the mere inflammation of the intestine. This is usually followed, within a variable number of years, with a more complicated disease phase, wherein strictures of the bowel (stenosing phenotype) and fistulas that form between affected intestines and other organs or areas of intestine (fistulizing phenotype) may occur. The symptoms vary according to disease phenotype and status (remission vs. flare), but mainly manifest as abdominal pain, diarrhea, fever, excess weight loss, and possible occurrence of sub-occlusive symptoms (cramping pain, vomiting, hard feces/gas evacuation) or other complications (i.e., abscesses, fistulas). Extraintestinal manifestation is not infrequent, and rheumatic and dermatological involvement occurs in up to 40% of patients . CD is usually a rare disease, but one with increasing frequency worldwide: incidence rates are up to 20.2 per 100,000 persons/12 months in North America and 12.7 per 100,000 persons/12 months in Europe. Prevalence rates are also up to 319 per 100,000 persons in North America and 322 per 100,000 persons in Europe . Among the so-called standard therapies, corticosteroids are still the mainstay of treatment for acute inflammatory flares, and budesonide , characterized by a more favorable safety profile, can be utilized for mild-to-moderate inflammatory flares [5,6]. Immunosuppressive treatments (thiopurines and methotrexate) have been partially scaled down with the introduction of biologics but are still indicated for maintenance of remission as steroid sparing brokers and in combination with infliximab for immunogenicity reduction . Salicylates, antibiotics, and probiotics may be used in SB 415286 specific situations, SB 415286 but they lack solid evidence for efficacy in CD patients [8,9]. Surgery represents a still frequent therapeutic option for CD patients, and it is generally indicated for Rabbit Polyclonal to TPIP1 medically refractory and complicated (stenosis, fistulas) conditions . In general, the goal of a successful therapeutic approach is usually induction and maintenance of disease remission; however, the specific definition of disease remission consistently has changed throughout the years. The target for successful therapy has changed from simple symptom control to the current identification of solid therapeutic endpoints such as clinical and biochemical normalization, mucosal and transmural healing patient reported outcomes (PROs), and quality of life. These are better indicators of complete short- and long-term SB 415286 disease control and are also related to a decreased rate of complications (steroid use, hospitalization, surgery) [11,12,13]..