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Background The inflammatory process associated to ulcerative colitis (UC) and Crohn’s disease (CD) starts before the onset of symptoms and the diagnosis, but this period has not yet been well defined. Our aim was to determine if patients with an incidental diagnosis of UC or CD have an increase in healthcare utilization in the years preceding the symptomatic onset of the disease. Methods All asymptomatic patients with a diagnosis of UC or CD during the colorectal cancer screening program between October 2010-January 2021 were included in this multicentric retrospective case-control study. Cases were matched 1:3 with controls adjusted by sex, age and date, excluding subjects with any visit to Gastroenterology. The main outcomes were the number of outpatient or Emergency Rooms visits, admissions, radiological examinations (US, CT, MRI), sick-leaves, and drug prescriptions (antibiotics, systemic steroids) up to 5 years before the diagnosis. Descriptive statistics were used, with chi-square tests and a multivariable hurdle or negative binomial regression model, adjusted by smoking habits and Charlson index. Results A total of 124 patients were included (87 UC, 30 CD, 7 IBD-U; median 56 years (IQR, 53–62); 56% male), compared with 372 controls. Baseline characteristics including comorbidities were balanced between both cohorts. Patients demonstrated an increase in the number of visits to Primary Care physician during both 3 and 5 years before the diagnosis, but there were no differences in the remaining outcomes including hospital admissions, Emergency Room or outpatients visits, and sick-leaves (Figure 1 and 2). Systemic steroids were more frequently prescribed to patients in the preceding 3 to 5 years before diagnosis. Patients underwent US and/or CT scan less frequently in the preceding 5-year period. Conclusion Patients with IBD show an increased need of medical assistance in the years prior to the diagnosis, even during the presymptomatic phase of the disease. Tools focused on early identification of IBD may start on Primary Care facilities, but certain factors as steroids may alter the development of symptoms and the full spectrum of the disease.

Background The use of ustekinumab (UST) and vedolizumab (VDZ) as first line therapy for inflammatory bowel disease (IBD) is increasing due to safety reasons and contraindications of anti-TNFs. However, there are no studies evaluating their efficacy and safety in clinical practice under these circumstances. Thus, our aims were to describe bionaïve patients’ characteristics starting VDZ or UST and to evaluate treatment persistence of these drugs and their safety profile in this scenario. Methods Descriptive, retrospective and multicenter study based on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD –GETECCU). All IBD patients never exposed to biological agents who started VDZ or UST as first-line biological treatment were identified. Results Out of 29,450 IBD patients ever exposed to biological drugs included in the ENEIDA registry, 924 patients met the inclusion criteria. Of these, 366 (40%) started UST and 558 (60%) VDZ as first line biological therapy. UST group: 48% women, 90% Crohn's disease (43% ileal; 13% colic; 43.5% ileocolic; 31% upper gastrointestinal involvement; 25% stricturing behaviour; 12% penetrating, 18% perianal disease), 10% ulcerative colitis (74% extensive, 17% left-sided, 9% proctitis), 27% had extraintestinal manifestations (EIM). Median age at the beginning of UST was 57 years (IQR 57-70), 17% patients had a past history of malignancy and, 34% had associated comorbidities. UST indication was luminal activity except in 2% for perianal disease and 5% for EIM. At the end of follow-up (median 14 months [IQR 6-30]), 12 patients (3.3%) developed adverse effects (AEs) that led to treatment discontinuation in the majority of them (92%). VDZ group: 44% women, 42% Crohn's disease (44% ileal; 18% colic; 38% ileocolic; 25% upper gastrointestinal involvement; 28% stricturing behaviour; 13% penetrating; 7% perianal disease), 58% ulcerative colitis (50% extensive, 42% left-sided, 8% proctitis), 17% had EIM. The median age at the beginning was 61 years (IQR 48-71), 24% had past history of malignancy and, 34% associated comorbidities. The indication was exclusively luminal activity. At the end of follow-up (median 21 months [IQR 8-36]), 36 patients (6.5%) had AEs, that lead to treatment withdrawal in 67% of them (24 patients). Cumulative treatment persistence rates were 78%, 60% and 50% for VDZ and 85%, 75% and 66% for UST at 12, 24 and 36 months, respectively (P Conclusion In clinical practice, VDZ and UST are used first-line particularly in elderly patients with comorbidities. Both treatments have a good safety profile and a high persistence of treatment, being superior for ustekinumab.

Background Diagnostic delay (DD) is defined as the time between the onset of the first symptoms and the definitive diagnosis of IBD. It is highly heterogeneous and it has a negative impact on the disease course. Our objective was to describe the main clinical and histological characteristics at diagnosis of UC according to the DD and its influence on clinical course. Methods A retrospective study compiled information from consecutive patients diagnosed with UC between January 2015 and December 2019 and included in the ENEIDA registry in our hospital. Patient and disease characteristics at diagnosis such as age, DD, disease extent, partial Mayo Score (PMS), extraintestinal manifestations (EIM), fecal calprotectin (FC), and histological characteristics at diagnosis were compiled. The role of DD was evaluated as both quantitative and dichotomous variable using Spearman correlation, chi-square and Mann-Whitney tests. Results A total of 146 patients (53% male; 47% former smokers; median age 46 years [IQR, 34-56]; 27% E2 and 35% E3; median FC of 289 mg/kg (IQR, 105-586) with a median DD of 2 months (IQR, 1 -4) were included. The median PMS at diagnosis was 2 points (IQR, 2-5), with higher scores in patients with shorter DD (≤2 months, median 3 points [IQR, 2-5] vs >2 months, median 2 points [IQR, 2-4]; p=0.002). Among them, 7% of patients presented at least one EIM, reported more frequently in patients with a DD >2 months (1.4% with DD≤2 vs 13.4% with DD>2 months; p=0.007; Figure A). During follow-up, 9% developed proximal disease extension. The most frequent histological findings were cryptic abscesses (71%), with a predominantly chronic infiltrate with basal plasmacytosis (97%), epithelial irregularity (83%), decreased mucosecretion (46%), erosions (21%), and ulceration (12%). The presence of eosinophils was more frequent as DD increases (5.6% if DD≤2 vs 18% if DD>2 months; p=0.029; Figure B), whereas the degree of chronic infiltration is more severe in patients with shorter DD (94% if DD≤2 vs 82% if DD>2 months; p=0.029; Figure C). Conclusion DD in UC influences the severity of clinical disease activity and the rate of EIM at diagnosis. In addition, eosinophils are more frequent as DD increases, while the degree of chronic infiltrate was more pronounced in patients with shorter disease duration.

Background Previous data have shown that the inflammatory process underlying ulcerative colitis (UC) and Crohn’s disease (CD) can start years before the diagnosis, but the role of triggering factors and environmental exposures is still unknown. Hair element analysis is a valuable and inexpensive screen for physiological excess or deficiency of certain elements. Our aim was to determine if patients with an incidental diagnosis of UC or CD demonstrate exposure of minerals or toxic metals in the years preceding the symptomatic onset of the disease. Methods We performed a prospective single-center study including all asymptomatic subjects with a diagnosis of UC or CD during the colorectal cancer screening program between January 2021 – June 2022 in Vizcaya (Basque Country, Spain). The diagnosis of IBD was established by a combination of clinical data, endoscopic findings suggestive of UC or CD, and after histologic confirmation. Cases were compared with a healthy non-IBD control population. An approximate hair sample of 0.25 g was obtained up to 3 months since diagnosis. We used a commercial kit that allows the investigation of 17 metals (Al, Sb, As, Ba, Be, Bi, Cd, Pb, Hg, Pt, Tl, Th, U, Ni, Ag, Sn, Ti) and 22 minerals (Ca, Mg, Na, K, Cu, Zn, Mn, Cr, V, Mo, B, I, Li, P, Se, Sr, S, Co, Fe, Ge, Rb, Zr). Descriptive statistics and non-parametric tests were used for comparisons between both groups. Results Three patients with preclinical IBD were included (median age 53 years; 67% male; all former smokers). Two of them had a diagnosis of UC (one left-sided colitis and one extensive colitis) and one with ileal CD. Extraintestinal manifestations were observed in one patient (33%). No family history of IBD was reported. Thirteen healthy controls with no relevant environmental exposures (median age 34 years; 69% female; 92% non-smokers). We found that cases demonstrated statistically significant higher concentrations of bismuth, sodium and boron compared to controls (Figure). In contrast, there was a lower exposure to uranium, zinc and germanium, with a trend towards lower copper levels among cases. Conclusion A range of environmental exposures can be identified during the preclinical phase of IBD. However, their relationship with the symptomatic onset and disease progression should be further explored.

Background Previous data have shown that the inflammatory process underlying ulcerative colitis (UC) and Crohn’s disease (CD) can start years before the diagnosis. Serum proteomic and serologic markers have been identified during this period, providing the opportunity for early detection of the initial immune disturbances. Our aim was to determine if patients with an incidental diagnosis of UC or CD demonstrate a serologic response based on antimicrobial antibodies, therefore preceding the symptomatic onset of the disease. Methods We performed a prospective single-center study including all asymptomatic subjects with a diagnosis of UC or CD during the colorectal cancer screening program and available data on antimicrobial antibodies between 01/10/2013 – 29/02/2022. The diagnosis of IBD was established by a combination of clinical data, endoscopic findings suggestive of UC or CD, and after histologic confirmation. ASCA IgA, ASCA IgG (EliA ASCA IgA/IgG, ThermoFisher) and ANCA (EUROPattern, PerkinElmer; EliA IgG, ThermoFisher) antibodies were determined. Positive results were considered above 10 U/mL for ASCA, 3.5 for ANCA-MPO and 2.00 for ANCA-PR3. Descriptive statistics were used. Results A total of 26 incidentally-diagnosed patients were included, 19 with UC (21% left-sided, 32% extensive; 53% former smokers), and 7 with CD (57% ileal, 29% colonic; 14% active smokers), with a median age of 51 years (IQR, 51-57). Three patients showed at least one positive test (12%). One patient (5%) with extensive UC showed positive ANCA results, and he developed symptoms 2 months after diagnosis. Two patients (28%) with CD (L2B2 and L1B1, according to Montreal classification) showed positivity to ASCA IgA/IgG at diagnosis, and both have remained asymptomatic after a median of 23 months. After a median follow-up of the whole cohort of 54 months (IQR, 26-67), 12 patients (46%) developed symptomatic disease. Conclusion A low proportion of patients with an incidental diagnosis of IBD demonstrate a serological response based on antimicrobial antibodies, suggesting that this situation corresponds to the initial phases of IBD when systemic immune disturbances might not be detectable yet.

Background Very few studies have reported updated data on the incidence, clinical evolution and treatment of inflammatory bowel disease (IBD) in Europe. Aims i) To assess the incidence of IBD in Spain; ii) to describe the main epidemiological and clinical characteristics of patients at diagnosis and the evolution of the disease; and iii) to explore the use of drug treatments in the biological era. Methods Prospective and population-based nationwide registry. Adult patients diagnosed with IBD -Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)- during 2017 in all the 17 Spanish administrative regions were included and will be followed-up for 5 years after diagnosis. Treatment was grouped into 5 categories: mesalazine (oral or topical), steroids (intravenous, oral or topical), immunomodulators (thiopurines, methotrexate or cyclosporine), biologics (anti-TNF, vedolizumab or ustekinumab) and surgery. Results 3627 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 millions of adult inhabitants (about 50% of the Spanish population) comprise the study cohort (Table 1). The overall incidence (cases/100.000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U. Incidence of CD was somewhat higher in Central Spain, while that of UC was higher in Northern Spain (Asturias and Navarra) (Figure 1). About 46% of patients had CD and 50% UC. Diagnosis delay was longer in CD than in UC (5 vs. 2 months, p < 0.01). The proportion of patients with symptoms at diagnosis was higher in UC than CD (94 vs. 89%, p < 0.01). By contrast, those with CD vs. UC had higher frequency of family history of the disease (18 vs. 13%, p < 0.01), tobacco smoking (38 vs. 12%, p < 0.01) and extraintestinal manifestations (12 vs. 6%, p < 0.01). At diagnosis, 18% of CD patients had structuring or fistulising behaviour, and 69% of UC patients had extensive colitis or left-sided colitis. During a median of 12-month of follow-up, 28% of patients were hospitalised (35% of CD and 22% of UC patients, p < 0.01). A total of 2.6% CD patients progressed to a more severe phenotype, and 2% UC patients developed a more extensive involvement. The cumulative exposure to different treatments is shown in Figure 2. Conclusion The incidence of IBD in Spain is quite high and similar to that reported in Northern Europe. IBD patients require the use of substantial therapeutic resources, which are greater in CD than in UC, and much greater than previously reported. One third of patients are hospitalised in the first year after diagnosis and over 5% undergo surgery. These results highlight the high burden of IBD as well as some of the important challenges faced by clinicians and healthcare systems to manage this costly and complex disease.

Background It has been reported that familial aggregation occurs in 10–20% of inflammatory bowel disease (IBD) patients1. Familial IBD has been associated with disease anticipation2 and with an increased need for immunosuppressants3 and surgery4. However, most studies were performed before the widespread use of biological agents and this may impact on the need for surgery. We aimed to compare the clinical outcomes of IBD (by means of the need for biological therapy and abdominal surgery) between familial and sporadic forms of IBD in the era of biological therapies. Methods Data were extracted from the ENEIDA registry by GETECCU, a Spanish, prospectively-maintained, IBD database in which more than 80 centers are participating. Only adult patients diagnosed with IBD since 2005 and prospectively followed in the registry since diagnosis were included. Familial IBD was defined as those cases with at least one first-degree relative diagnosed with IBD. Sporadic IBD was defined as those cases with no familial relative (of any degree) with IBD. Kaplan-Meier survival curves were performed to evaluate the cumulative probabilities of remaining biologic-free and surgery-free. Log-rank test was performed to compare them between familial and sporadic IBD forms. Chi-square test was performed for the rest of variables. Results A total of 5,263 patients (2,627 Crohn’s disease [CD]; 2,636 ulcerative colitis [UC]) were included. Of them, 507 (10%) were familial cases (274 CD, 233 UC; P=0.05). The median follow-up was 38,4 and 35.5 months, respectively (P=0.086). Familial cases were younger (P=0.022) and had a higher proportion of females among UC cases (P=0.048). No differences were observed in the need for biological therapy in both CD and UC between familial and sporadic IBD. Regarding surgery, no differences were observed in the cumulative probabilities of a first intestinal resection for CD and colectomy for UC. Similar results were obtained when all the analyses were restricted to those subgroups at high-risk for surgery (i.e. CD with ileal involvement and extensive UC). Conclusion In patients diagnosed with IBD in the era of biological therapies, familial forms have the same requirements for biological agents and resectional surgery as sporadic forms. Therefore, familial aggregation does not seem to be a factor for a more aggressive disease.

The concept of inflammatory bowel disease (IBD) covers three entities: ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis (IC). These diseases have in common a chronic and relapsing course, alternating periods marked by inflammatory activity with other quiescent periods, in which the patient is asymptomatic. For many years treatment of the disease, especially in acute phases, was based on the use of corticoids. However, in recent decades we have witnessed significant advances from the therapeutic point of view. It is estimated that during the course of the disease's evolution 80% of patients will need corticoids, 40% immunomodulators (IMM), and as many as 20% will require a biological medicine to control their disease. While all of this is accompanied by an improvement in quality of life, less hospital admissions or surgical interventions, their use also involves an increase in the risk of suffering infections, either due to germs normally found in the community or opportunistic infections. Moreover, infections are a cause of morbidity and mortality associated with IBD and some of them can be prevented with vaccinations, hence the importance that vaccination programs are acquiring in this groups of patients. We present a review of the relevant literature and propose a vaccination protocol for patients diagnosed with IBD.

Low thiopurine-methyl-transferase (TPMT) activity and high 6-thioguanine-nucleotide (6TGN) concentrations have been linked to therapeutic success in inflammatory bowel disease patients treated with thiopurines; however, this has not been implemented in clinical practice.To identify a therapeutic threshold value for TPMT or 6TGN concentrations, and their capability to predict treatment safety and efficacy.Prospective multicentre study including steroid-resistant/dependent patients starting thiopurines. The TPMT activity was determined at inclusion (5 U/mL required). Azathioprine metabolites [6TGN, 6-methyl-mercaptopurine ribonucleotides (6MMP), and 6TGN/6MMP and 6TGN/TPMT ratios] were periodically monitored during steroid tapering and after withdrawal for 6 months or until a new flare occurred.A total of 113 patients were analysed (62% clinical response). Areas under the receiver operating characteristic (ROC) curve (AUC) relating clinical response and metabolite levels at 2, 4 and 6 months after steroid withdrawal were less than 0.7. The AUCs relating final response and initial TPMT activity or metabolite concentrations at 2, 4, 8 and 16 weeks after starting thiopurines were less than 0.7. No cut-off point with worthwhile sensitivity/specificity was found. Eight (7%) patients developed thiopurine-related toxicity that could not be linked to TPMT activity or 6TGN levels.Our results do not support determination of TPMT activity or 6TGN concentrations to predict treatment outcome, and no useful serum metabolites threshold value to adjust the drug's dose was identified.

The use of tumour necrosis factor antagonists has changed the therapeutic approach to Crohn's disease.To determine response and remission rates associated with the 4-week induction phase of adalimumab treatment in patients with luminal and/or fistulizing Crohn's disease, who have lost response to or become intolerant of infliximab.In this multicentre, prospective, open-label, observational, 52-week study, 50 adults received an induction dose of adalimumab (160 mg at baseline followed by 80 mg at week 2).Of the 36 patients with luminal Crohn's disease, 83% achieved clinical response [or =70-point reduction in the Crohn's Disease Activity Index (CDAI) score] and 42% achieved clinical remission (CDAI score150) at week 4. Of the 22 patients with fistulizing disease, five (23%) experienced fistula remission (complete closure of all fistulas that were draining at baseline), and nine (41%) experienced fistula improvement (or =50% decrease in the number of fistulas that were draining at baseline) at week 4. Of the 19 adverse events, most [13 (68%)] were mild, and no serious or infectious adverse events occurred.Adalimumab may be an effective alternative in patients with luminal and/or fistulizing Crohn's disease who have lost response to or become intolerant of infliximab.

The importance of colonic polyp is increasing because colorectal cancer (CRC) screening is based on their identification. However, consensus is lacking on which technique should be used in CRC screening, whether colonoscopy or other methods such as sigmoidoscopy, which shows good sensitivity only in distal segments of the colon. We studied the characteristics and localization of polyps in our environment to verify their tendency to change localization and determine the implications of this in screening.We reviewed the prevalence and characteristics of colonic polyps in 3604 patients who underwent colonoscopy for various causes in our service, as well as their distribution in 837 patients with a diagnosis of polyps who underwent complete colonoscopy. Localization proximal or distal to the splenic flexure and polyp size (less than or more than 1 cm) were analyzed.Polyps were found in 28.3% of 3604 patients (11.7% showed polypsor = 1 cm). Of the 837 patients who underwent complete colonoscopy, proximal polyps were found in 44.9% (14.6% showed polypsor = 1 cm), while distal polyps were found in 79.9% (30.3% showed polypsor = 1 cm). Both proximal and distal polyps were found in 24.8%. The probability of finding both proximal and distal lesions was 31%. Proximal lesions without distal lesions were found in 20% of the patients (5.6% presented polypsor = 1 cm), and consequently sigmoidoscopy would miss 15.6% of polypsor = 1 cm.A relatively high percentage of patients with proximal polypsor = 1 cm would remain undiagnosed if complete colonoscopy were only performed in patients with distal polyps. Because of the well-known increase in the frequency of proximal polyps and because a considerable number of these present without distal sentinel lesions, there are increasing arguments for considering colonoscopy as the basic technique for CRC screening.