The fifth scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on the relevance of fistulas to the disease course of patients with Crohn's disease (CD). The objectives were to reach a better understanding of the pathophysiological mechanisms underlying the formation of CD fistulas; to identify future topics in fistula research that could provide insights into pathogenesis; to develop novel therapeutic approaches; and to review current therapeutic strategies (with clarification of existing approaches to prevention, diagnosis and treatment). The results of the workshop are presented in two separate manuscripts. This manuscript describes current state-of-the-art knowledge about fistula pathogenesis, including the roles of epithelial-to-mesenchymal transition and cytokine matrix remodelling enzymes, and highlights the common association between fistulas and stenosis in CD. The review also considers the possible roles that genetic predisposition and intestinal microbiota play in fistula development. Finally, it proposes future directions and needs for fistula research that might substantially increase our understanding of this complex condition and help unravel novel therapeutic strategies and specific targets for treatment. Overall, it aims to highlight unanswered questions in fistula research and to provide a framework for future research work.

BACKGROUND: Inflammatory bowel diseases (IBD) are chronic inflammatory affections of recurrent nature whose incidence and prevalence rates have increased, including in Brazil. In long term, they are responsible for structural damage that impacts quality of life, morbidity and mortality of patients. OBJECTIVE: To describe the profile of physicians who treat IBD patients as well as the characteristics of IBD care, unmet demands and difficulties. METHODS: A questionnaire containing 17 items was prepared and sent to 286 physicians from 101 Brazilian cities across 21 states and the Federal District, selected from the register of the State Commission of the “Study Group of Inflammatory Bowel Disease of Brazil” (GEDIIB). RESULTS: The majority of the physicians who answered the questionnaire were gastroenterologists and colorectal surgeons. More than 60% had up to 20 years of experience in the specialty and 53.14% worked at three or more locations. Difficulties in accessing or releasing medicines were evident in this questionnaire, as was referrals to allied healthy professionals working in IBD-related fields. More than 75% of physicians reported difficulties in performing double-balloon enteroscopy and capsule endoscopy, and 67.8% reported difficulties in measuring calprotectin. With regard to the number of patients seen by each physician, it was shown that patients do not concentrate under the responsibility of few doctors. Infliximab and adalimumab were the most commonly used biological medicines and there was a higher prescription of 5-ASA derivatives for ulcerative colitis than for Crohn’s disease. Steroids were prescribed to a smaller proportion of patients in both diseases. The topics “biological therapy failure” and “new drugs” were reported as those with higher priority for discussion in medical congresses. In relation to possible differences among the country’s regions, physicians from the North region reported greater difficulty in accessing complementary exams while those from the Northeast region indicated greater difficulty in accessing or releasing medicines. CONCLUSION: The data obtained through this study demonstrate the profile of specialized medical care in IBD and are a useful tool for the implementation of government policies and for the Brazilian society as a whole.

Introduction: There is currently an increasing use of biological agents in the management of Crohn's disease (CD). There is lack of data regarding the epidemiological profile of patients on infliximab (IFX) and adalimumab (ADA) for CD in Brazil. Objective: To identify the epidemiological characteristics of patients with CD who underwent biological therapy. Method: Retrospective multicenter study, with CD patients on biological therapy. Analyzed variables: gender, age at treatment initiation, Montreal classification, concomitant perianal disease and smoking status. Results: 175 patients without previous exposure to biological agents were included, 93 (53%) were male. The mean age at treatment initiation was 35.5 (2-79) years old an the mean disease duration was 46.9 (0-480) months. Overall, 117 (66.9%) patients used IFX and 58 (33.1%), ADA. Montreal classification: age at diagnosis-A1 (n=21; 12%), A2 (n=102; 58.3%), and A3 (n=52; 29.7%). CD location-L1 (n=42; 24%), L2 (n=51; 29.1%), L3 (n=81; 46.3%), and L4 (n=1, 0.6%). Phenotype-B1 (n=59; 33.7%), B2 (n=46; 26.3%), and B3 (n=70; 40%). Perianal disease was found in 89 (50.9%) patients. Conclusions: The epidemiological profile of patients was similar to the literature. There was a high prevalence of patients with fistulizing CD.

BACKGROUND: There is scarce data regarding efficacy and safety of vedolizumab in inflammatory bowel diseases in Latin America. OBJECTIVE: To describe the first observational real-world experience with vedolizumab in Latin American inflammatory bowel diseases patients. METHODS: Retrospective observational multicentric study of patients with Crohn’s disease (CD) and ulcerative colitis (UC) who used vedolizumab at any phase of their treatment. Clinical remission and response (according to Harvey-Bradshaw index for CD and Mayo score for UC), mucosal healing, need for surgery and adverse events were evaluated. RESULTS: A total of 90 patients were included (52 with CD and 38 with UC), the majority with previous exposure to anti-TNF agents (88.46% in CD and 76.31% in UC). In CD (as observed analysis) remission rates at weeks 12, 26 and 52 were 42.89% (21/49), 61.9% (26/42) and 46.15% (12/26), respectively. In UC, remission rates at weeks 12, 26 and 52 were 28.94% (11/38), 36.66% (11/30) and 41.17% (7/17). Mucosal healing rates were 36.11% in CD and 43.4% in UC. During the study period, 7/52 CD patients underwent major abdominal surgery and 4/38 UC patients needed colectomy. CONCLUSION: Vedolizumab was effective in induction and maintenance of clinical response and remission in CD and UC, with no new safety signs.

-Background -Adalimumab is a monoclonal antibody, tumor necrosis factor-alpha (TNFα) inhibitor that has efficacy for inducing and maintaining remission in moderate-to-severe ulcerative colitis. Real world studies with adalimumab in Latin American ulcerative colitis patients are scarce.Objective -To assess the clinical remission rates in induction and maintenance with adalimumab therapy in ulcerative colitis. Declared conflict of interest of all authors: Damião AOMC (Nestle, Janssen, Abbvie, Pfizer and Takeda), Moraes AC (Janssen, Abbvie, Takeda), Teixeira FV (Janssen, Abbvie, Ferring, Takeda, Pfizer), Ludvig JC (Janssen, Abbvie, Takeda), Nones RB (Abbvie, Takeda), Saad-Hossne R (Janssen, Abbvie), Sassaki LY (Janssen, Abbvie, Takeda), Kotze PG (Janssen, Abbvie, Ferring, Takeda, Pfizer The rate of colectomy in ULTRA II trial was less than 5%, without stratification regarding the previous use of another anti-TNF agent (8) . The drug was approved by Food and Drug Administration (FDA) and National Sanitary Surveillance Agency (ANVISA), in 2012 and 2014, respectively (14) . Despite the results of the clinical trials, there is a discrepancy between those and real world data in UC (15) , similar to what was observed in terms of efficacy of ADA in Crohn's disease (CD) (13) . Retrospective studies of case series tend to have higher effectiveness rates than randomized trials, which have a more strict analysis. Furthermore, it is enquired what the ideal dose of ADA in the management of UC would be needed (12) , showing the need of data from real life studies to better define the drug's role in treatment algorithms. There is scarce real world data on the use of ADA in UC reported in Brazil and Latin America, which motivated the present study (1,2,9,10,18,28,29) . The primary aim of this study was to analyze clinical remission rates in ADA induction and maintenance in UC treatment. Secondary objectives were to analyze clinical response, endoscopic remission, colectomy rates, adverse events, and secondary loss of response, besides dose optimization or drug switching during the follow-up period. Adalimumab for ulcerative colitis: results of a Brazilian multicenter observational study METHODS Study designThis was a longitudinal, analytical, observational and retrospective study of a case series of patients with moderate-to-severe UC under ADA therapy. All patients were treated in seven referral centers for inflammatory bowel disease (IBD) from south/southeast Brazil, and were analyzed from