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No studies evaluating the rapidity of response to biological therapies are available for Crohn's disease (CD). The aim of this study was to evaluate rapidity of onset of clinical response and impact on quality of life (QoL) of adalimumab therapy in adult anti-TNF-naïve patients with moderately-to-severely active CD.RAPIDA was an open-label, single-arm, prospective, multicenter clinical trial. Adult patients with moderately-to-severely active luminal CD, anti-TNF-naïve, and unresponsive to conventional therapy were treated with adalimumab. Clinical disease activity, QoL and inflammatory biomarkers were measured at day 4, and weeks 1, 2, 4, and 12 after treatment initiation.Eighty-six patients were included in the intention-to-treat (ITT) analyses. Clinical disease activity was reduced from a median of 9.0 points to 6.0 points at day 4. Clinical response (≥ 3-point reduction in the Harvey-Bradshaw Index, HBI) was achieved by 61.6% (d4) and 75.6% (w1) of patients in the ITT population (median 2.5 days) and with non-responder imputation (NRI), by 55.8% and 53.4%, respectively. The proportion of patients in clinical remission (HBI5) at weeks 2 and 4 in the ITT population was 54.7% and 62.8%, respectively (median 7.0 days), and 38.4% and 45.3% in the NRI population. All QoL scores significantly improved and inflammatory biomarkers significantly decreased from day 4 onwards (p0.0001).Rapid clinical response and remission, improvement in QoL and fatigue, and a reduction of inflammatory biomarkers were achieved with adalimumab as early as day 4 in adult anti-TNF-naïve patients with moderately-to-severely active CD.

Resumen Objetivo La ecografia intestinal se considera una alternativa para la evaluacion de la recurrencia posquirurgica (RPQ) de la enfermedad de Crohn. El objetivo de este estudio es evaluar la correlacion entre los hallazgos ecograficos y endoscopicos. Metodos Se recogieron de forma retrospectiva los datos de pacientes con enfermedad de Crohn y reseccion ileocecal en los que se habia realizado una colonoscopia y una ecografia intestinal para la deteccion de RPQ. La RPQ se evaluo empleando el indice de Rutgeerts (IR). Los hallazgos ecograficos analizados fueron el grosor de la pared intestinal, la hiperemia parietal por Doppler, la desestructuracion del patron de capas y la proliferacion fibrograsa. Resultados Se incluyo a un total de 31 pacientes, 15 (48,4%) sin recurrencia (IR? Conclusiones En nuestra experiencia, la ecografia tiene una alta rentabilidad diagnostica para la deteccion de RPQ y puede considerarse en muchas ocasiones como una alternativa valida y no invasiva a la ileocolonoscopia.

BACKGROUND Crohn's disease (CD) with upper gastrointestinal involvement (UGI) may have a more aggressive and refractory course. However, evidence on this phenotype of patients is scarce. AIMS To identify the clinical characteristics, therapeutic requirements and complications associated with UGI in CD METHODS: Nationwide study of cases (UGI, UGI plus ileal/ileocolonic involvement) paired with controls (ileal/ileocolonic involvement) from the ENEIDA registry. Cases were matched to 2 controls by year of diagnosis ± 2.5 years. Patients with exclusive/predominant colonic location or complex perianal fistula were excluded. RESULTS Of 24 738 patients with CD in the ENEIDA registry, we identified 4058 with UGI (16% of the total CD cohort). Finally, 854 cases and 1708 controls were included. Cases were independently associated to extensive involvement (OR 2.7 [2.2-3.3], P

Background: A treat-to-target strategy, in which strictly defined treatment targets facilitate decision making in clinical practice, is advocated as an optimised management approach for some chronic disorders. The aim of the STARDUST trial was to assess whether a treat-to-target strategy with early endoscopy, regular biomarker and clinical symptom monitoring, and dose intensification for persistent inflammatory activity, was more successful in achieving endoscopic improvement at week 48 than a clinically driven maintenance strategy in patients with moderate-to-severe active Crohn's disease receiving ustekinumab. Methods: This open-label, multicentre, randomised phase 3b trial included adults with active, moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220–450 and Simple Endoscopic Score in Crohn's Disease [SES-CD] ≥3) for whom conventional therapy or one biologic therapy, or both, had failed. Patients received intravenous ustekinumab approximating 6 mg/kg at baseline and subcutaneous ustekinumab 90 mg at week 8. At week 16, patients with a CDAI improvement of 70 or more points from baseline were randomly assigned (1:1) to receive standard-of-care or treat-to-target maintenance treatment through week 48. Randomisation was balanced by using randomly permuted blocks and was stratified by biologic history status and baseline SES-CD score. All patients who signed informed consent, who were not screening failures, and who received at least one dose of study treatment were included in week 16 analyses. All patients included in week 16 analyses and randomly assigned to one of the maintenance treatment regimens were included in the week 48 efficacy and safety analyses (ie, on an intention-to-treat basis). Patients assigned to the treat-to-target arm received ustekinumab every 12 weeks or every 8 weeks based on SES-CD improvement from baseline and could escalate to every 4 weeks through week 48 if prespecified targets were missed. Patients assigned to the standard-of-care arm received ustekinumab every 12 weeks or every 8 weeks; those receiving treatment every 12 weeks could escalate per European labelling. The primary efficacy endpoint was endoscopic response at week 48 (SES-CD score ≥50% decrease from baseline), analysed by non-responder imputation. This trial is registered at ClinicalTrials.gov, NCT03107793, and is active but not recruiting. Findings: 498 patients received standard induction treatment, of whom 440 were randomly assigned to the treat-to-target group (n=219) or the standard-of-care group (n=221). At week 48, there was no significant difference in endoscopic response (83 [38%] of 219 patients vs 66 [30%] of 221 patients; p=0·087), endoscopic remission (25 [11%] vs 32 [15%]; p=0·334), mucosal healing (31 [14%] vs 37 [17%]; p=0·449), and clinical remission (135 [62%] vs 154 [70%]; p=0·072) between the two groups; clinical response was significantly lower in the treat-to-target group than in the standard-of-care group (149 [68%] vs 172 [78%]; p=0·020). Other endoscopic, clinical, and biomarker outcomes were generally not significantly different between groups. The most commonly reported treatment-emergent adverse events were nasopharyngitis (29 [13%] of 219 patients in the treat-to-target group vs 29 [13%] of 221 patients in the standard-of-care group), abdominal pain (23 [11%] vs 19 [9%]), arthralgia (24 [11%] vs 19 [9%]), and headache (24 [11%] vs 21 [10%]). Interpretation: Timely escalation of ustekinumab therapy for patients with Crohn's disease, based on early endoscopic response, clinical symptoms, and biomarkers, did not result in significantly better endoscopic outcomes at week 48 than symptom-driven decisions alone. Future studies need to confirm if some subgroups of patient might benefit from a treat-to-target strategy with ustekinumab. Funding: Janssen-Cilag.

Malaltia de Crohn; Factors predictius; Ustekinumab Enfermedad de Crohn; Factores predictivos; Ustekinumab Crohn’s disease; Predictive factors; Ustekinumab Ustekinumab has shown efficacy in Crohn’s Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients’ data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission. This work was supported by Janssen-Cilag Spain. This sponsor had a partial role in study design, analysis, and interpretation of data.

Background and Aims Clinical trials and real-life studies with ustekinumab in Crohn’s disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. Methods Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey–Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. Results In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. Conclusions Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.

Background Post-marketing data are required to confirm the durability and the long-term benefit and safety of UST in CD in clinical practice. Our aims were: (1) to evaluate the retention rate of UST in CD patients and to identify predictive factors of UST discontinuation; (2) to assess UST short-term effectiveness; (3) to analyse the durability of the response to UST in the long-term; and (4) to evaluate the safety of UST in clinical practice. Methods Retrospective, multicentre study (>60 centres). Patients with active CD [(Harvey–Bradshaw (HBI) >4)] that received at least one dose of UST intravenously before July 2018 were included. Clinical activity plus biochemical parameters were assessed at every UST administration. Clinical remission was defined as HBI score ≤4, and clinical response as a decrease in HBI ≥3 points. Loss of efficacy was defined as reappearance of symptoms that led to intensify the treatment dose, add another medication to control CD, switching or surgery in patients with short-term remission. The retention rate of UST treatment and the cumulative incidence of loss of efficacy were evaluated by survival curves, and predictive factors were assessed by Cox-regression. The short-term response was evaluated at week 8 and after the induction (week 16). Factors associated with short-term remission were assessed by multivariate analysis. Adverse events were recorded. Data quality was assured by remote monitoring. Results 331 CD patients have been included up to date (Table 1). The incidence rate of UST discontinuation was 15% per patient-year of follow-up: 8%, 13% and 20% at 6, 12 and 18 months (Figure 1). Previous surgery was the only factor associated with a higher risk of UST discontinuation [Hazard ratio (HR) = 2.03, 95% confidence interval (CI) = 1.1–3.6]. Short-term efficacy is shown in Figure 2. Previous surgery (OR = 0.3, 95% CI = 0.2–0.6) and higher HBI score at baseline (OR = 0.8, 95% CI=0.8–0.9) were associated with an impaired response to UST at week 16. The cumulative incidence of loss of response was 32% per-patient-year of follow-up (Figure 3); A higher HBI score at baseline was associated with a higher risk of losing response (HR = 1.2, 95% CI = 1.1–1.3). Neither the concomitant treatment with immunosuppressants nor the number of previous biologics were associated with UST short- and long-term benefit. Thirty adverse events were reported in 25 (7%) patients (Table 2). Conclusion Sustain is the largest real clinical practice study of UST to treat CD patients with the longest follow-up reported to date. UST was demonstrated to be effective in real-world use in the short and long run. Safety was consistent with the known profile of UST.

BACKGROUND: There is no information regarding the outcome of Crohn's disease (CD) patients treated with endoscopic balloon dilation (EBD) in non-referral hospitals, nor on the efficacy of EBD in ulcerative colitis (UC). We report herein the results of the largest series published to date.; AIM: To assess the efficacy and safety of EBD for inflammatory bowel disease (IBD) stenosis performed in 19 hospitals with different levels of complexity and to determine factors related to therapeutic success.; METHODS: We identified IBD patients undergoing EBD in the ENEIDA database. Efficacy of EBD was compared between CD and UC and between secondary and tertiary hospitals. Predictive factors of therapeutic success were assessed with multivariate analysis.; RESULTS: Four-hundred dilations (41.2% anastomotic) were performed in 187 IBD patients (13 UC/Indeterminate colitis). Technical and therapeutic success per dilation was achieved in 79.5% and 55.3%, respectively. Therapeutic success per patient was achieved in 78.1% of cases (median follow-up: 40months) with 49.7% requiring more than one dilation. No differences related to either diagnosis or hospital complexity was found. Technical success [OR 4.12 (95%CI 2.4-7.1)] and not receiving anti-TNF at the time of dilation [OR 1.7 (95% CI 1.1-2.6)] were independently related to therapeutic success per dilation. A stricture length=2cm [HR 2.43 (95% CI 1.11-5.31)] was a predictive factor of long-term success per patient. The rate of major complications was 1.3%.; CONCLUSIONS: EBD can be performed with similar efficacy and safety in hospitals with differing levels of complexity and it might be a suitable treatment for UC with short stenosis. To achieve a technical success and the short length of the stenosis seem to be critical for long-term therapeutic success.

Background A less aggressive phenotype of Crohn’s disease (CD) has been reported in patients with elderly onset CD. Despite this, similar surgical rates among younger and older CD patients have been reported. However, scarce data are available about the risk of postoperative recurrence (POR) regarding the age, and no data are available about the use of immunosuppressants and biological agents for prevention of POR in elderly patients. Our aim was to evaluate the management of CD in the postoperative setting and the rate of surgical POR in CD patients according to the age at surgery. Methods Cohort study including all adult CD patients in the ENEIDA registry (a prospectively-maintained database of the Spanish Working Group in IBD –GETECCU-) who underwent a first intestinal resection with ileo-colonic anastomosis. Patients were grouped regarding their age at the moment of the first surgery: over 60 years (elderly) and between 18 and 60 years of age (controls). Preventive treatment for POR, surgical POR (need for a further intestinal resection) and postoperative morbidity were compared between both groups. Results Out of the 69,740 IBD patients included in the ENEIDA database, 3,982 had a first intestinal resection for Crohn’s disease with an ileo-colonic anastomosis between 2005 and 2020. Of them, 535 were elderly and 3,454 controls. Time from IBD diagnosis to surgery was significantly longer in the elderly (114±128 vs. 93±97 months; p Conclusion The elderly patients show similar rates of surgical POR as compared to younger patients. Given the high risk of thiopurine and anti-TNF-related adverse events, elderly patients with inflammatory pattern would benefit from preventive therapy with safer biologicals.

Bakground and Aim: Predictors of the need for surgery in sticturing Crohn’s disease (SCD) are lacking. Bowel ultrasound (US) is a harmless, noninvasive, and inexpensive diagnostic procedure that has proven to be a valuable tool in the management of Crohn’s disease (CD). Our aim was to identify ultrasonographic findings in SCD that may associate with a higher risk of surgery, allowing us to make early choices regarding treatment election in this specific group of patients. Materials and Methods: This was a retrospective, case-control study. Twenty-four patients diagnosed with SCD between 2013 and 2017 with a past history of stricture-related surgery were included and then matched with 46 non-operated controls. Prior US from patients in both groups were analyzed. US features considered for analysis were as follows: bowel wall thickness, degree of parietal vascularization (measured by Doppler activity), prestenotic dilation, involvement of mesenteric fat, and newly detected concomitant fistulas or abscess. Results: Doppler activity (p < 0.001), enteroenteric fistulas (p = 0.04), enteromesenteric fistulas (p = 0.003), and associated abscess (p = 0.004) were significantly associated with the need for surgery in the short-term period. Multivariate analysis showed strong association of these features with the risk of surgery but failed to reach statistical significance. Conclusion: US features may potentially be used as point-of-care tools to aid clinicians in the assessment of the surgical risk in patients with SCD.

Aims The aims of this study were (a) to know the kinetics of antitumor necrosis factor (TNF) drug serum levels during the induction phase in patients with Crohn's disease; (b) to identify variables associated with these levels; and (c) to assess the relation between these levels and short-term effectiveness in Crohn's disease patients. Methods Patients with Crohn's disease naive to anti-TNF treatment were prospectively included. Remission was defined as a Crohn's disease activity index (CDAI) score 150 at study entry. At week 14, 52 out of 71 patients with CDAI > 150 at baseline (73%) had clinical remission. There were no differences in infliximab levels between patients with and without remission (8 vs. 9.1 mu g/mL, P > 0.05) or with and without response (7 vs. 11 mu g/mL, P > 0.05) at week 14. There was a trend to higher levels of adalimumab concentration in responders in comparison with nonresponders (13 vs. 6.7 mu g/mL, P = 0.05) and in patients who achieved remission in comparison with nonremitters (13.5 vs. 8.4 mu g/mL, P = 0.06). In the multivariate analysis, no variable was predictive of short-term remission, including infliximab and adalimumab serum levels. Conclusion Determining anti-TNF serum levels during the induction phase is not useful for predicting short-term remission in patients with Crohn's disease.

Background The effectiveness of the switch to another anti–tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8–3; P < 0.0001) and ulcerative colitis vs Crohn’s disease (HR, 1.6; 95% CI, 1.1–2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

Background: Surgery in Crohn’s disease (CD) may be associated with poor prognosis and clinical and surgical recurrence. The aim of this study was to describe and compare the post-operative management and outcomes of patients with CD who underwent first vs recurrent surgeries. Methods: Observational study that included adult CD patients from 26 Spanish hospitals who underwent ileocolonic resection with ileocolonic anastomosis between January 2007 and December 2010. Data were retrospectively collected from the medical records. Results: Data from 314 patients were analysed, of whom 262 (83%) underwent first surgery and 52 (17%) referred to previous CD surgeries. Baseline characteristics were similar between the two groups except for a higher rate of stricturing behavior at diagnosis among re-operated patients (P¼0.03). After surgery, a higher proportion of re-operated patients received prophylactic treatment with immunomodulators compared with patients with first surgery (P¼0.04). In re-operated patients, time to clinical recurrence was not associated with the fact of receiving or not prophylaxis, whereas, in patients with first surgery, recurrence-free survival was greater when prophylaxis was received (P¼0.03). Conclusions: After surgery, a higher proportion of patients with previous surgeries received prophylactic treatment with immunomodulators compared with patients with first surgery. Although prophylactic treatment was beneficial for preventing clinical recurrence in patients operated on for the first time, it did not significantly reduce the risk of further recurrence in patients with previous surgeries. This suggests that effective prophylactic therapies are still needed in this subset of patients, This study was funded by Merck Sharp & Dohme of Spain, a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, USA

This study is aimed at describing the prevalence of and risk factors associated with early post-operative complications after Crohn’s disease-related intestinal resection. Methods: This was a retrospective analysis of data from the PRACTICROHN cohort. Adult Crohn’s disease patients who underwent ileocolonic resection with ileocolonic anastomosis between January 2007 and December 2010 were included. The complications evaluated included death, ileus, anastomotic leak, abscess, wound infection, catheter-related infection, digestive bleeding and other extra-abdominal infections that occurred in the 30 days after surgery.Results: A total of 364 patients (median age at surgery 38 years and 50% men) were included. Indication for surgery was: stricturing disease (46.4%), penetrating disease (31.3%), penetrating and stricturing disease (14.0%) or resistance to medical treatment (5.8%). Early complications were recorded in 100 (27.5%) patients, with wound infection, intra-abdominal abscess and anastomotic leakage being the most frequent complications. Median hospitalization duration was 16 days for patients with complications vs. 9 days without complications (P, This study was supported by Merck Sharp and Dohme, Spain

Background : In patients with Crohn's disease (CD), endoscopic recurrence precedes clinical recurrence after ileocolonic resection. Guidelines recommend ileocolonoscopy within the first year after surgery. The study examined endoscopic monitoring and treatment decisions in CD patients in a real-world setting. Methods : The Practicrohn study involved adult patients from 26 Spanish hospitals who underwent ileocolonic resection with anastomosis from 2007 to 2010. Medical records data were collected retrospectively from diagnosis to index surgery and up to 5 years after surgery. Results : Of 314 analyzed patients, 262 (83%) underwent endoscopic evaluation, but only 30% (n = 95) had planned endoscopy as part of follow-up within the first year after surgery. An upward trend was observed in the proportion of endoscopies performed or planned within the first year after surgery across the selection period. More patients with than without endoscopic recurrence in the first year after surgery had a medication change, mainly for endoscopic activity in the absence of clinical symptoms (54 vs 13%; p = 0.02). Conclusions : Between 2007 and 2010, endoscopic monitoring of patients within the first year after CD-related surgery was less than adequate based on current standards, but showed improvement. Medication changes were in general agreement with current guideline recommendations. This work was presented as a poster (number P686) by M. Barreiro-de Acosta et al. at ECCO (European Crohn's and Colitis Organisation) '18 in Vienna, Austria, 14-17 February 2018.

Background: In APPRECIA trial, Crohn's disease (CD) patients undergoing intestinal resection were randomized to postoperative adalimumab (ADA) or azathioprine (AZA). Aims: To evaluate health-related quality of life (HRQoL) in APPRECIA trial. Methods: HRQoL was evaluated using disease-specific shortened Spanish version of the IBDQ (SIBDQ-9) and generic European Quality of Life-5 Dimensions (EQ-5D) questionnaires, completed at baseline and at weeks 24 and 52. Results: Sixty-one patients (37 ADA and 24 AZA) had evaluable data for HRQoL. Patients treated with ADA or AZA had significant improvement from baseline to weeks 24 and 52 in SIBDQ-9 and EQ-5D (p < 0.001 and p = 0.006 for all comparisons, respectively). There were no differences between treatment arms in mean change in SIBDQ-9 and EQ-5D at weeks 24 and 52 vs baseline. Only patients without endoscopic recurrence had significant improvement in SIBDQ-9 (p < 0.001) and EQ-5D (p < 0.001) at week 52. At week 52, there was a high to moderate negative correlation between CDAI score with SIBDQ-9 score( Pearson's r: -0.768) and with EQ-5D index (r: -0.644). Conclusion: HRQoL improved after intestinal resection in CD, irrespective of the postoperative therapyused (ADA or AZA). Outcomes in HRQoL were associated with prevention of endoscopic recurrence, sinceimprovements in HRQoL were only significant in patients with endoscopic remission at 1 year. (c) 2019 Editrice Gastroenterologica Italiana S. r. l. Published by Elsevier Ltd. All rights reserved.

Background Malnutrition is a frequent problem in inflammatory bowel disease (IBD) due to the increase in caloric consumption because of the pathology itself and due to the reduced intake. This low intake is mainly caused by the symptoms and the anorexia associated with the disease, but it is more and more common for patients to adopt elimination diets. Our aim was to investigate the general ideas about nutrition in patients with IBD, as well as to determine whether they consider that health professionals value the nutritional aspect. Methods Inclusion of patients with an established diagnosis of IBD followed-up in the unit of the Hospital Universitario La Paz, using an anonymised survey for the researcher and for the attending physician. Results A total of 118 patients were included, of which 56% (65 patients) were women. The mean age of the patients was 48.84 years (SD 14.2). All patients had a previous diagnosis of IBD: 51.7% (61 patients) ulcerative colitis (UC), 45% (53 patients) Crohn’s disease (CD) and 3.3% (4 patients) undetermined colitis. 55.6% (64 patients) believed that nutrition influenced the course of their IBD. The patients who answered yes were on average younger (44.5 vs. 53.9 years), these differences being statistically significant (p = 0.0003). Only 22 of the 64 patients (34.4%) believed that it was caused by a specific food or food group and the most frequent answer was food rich in fats, dairy products, alcohol or spices. 52.1% of the sample (61 patients) had eliminated some food from the diet since the diagnosis of IBD. The most noteworthy was the avoiding of dairy products (37%), fibre in 28% (most of them reducing the intake of fruits and vegetables), alcoholic drinks (17%) and carbonated drinks (11.5%). No statistically significant differences were found in the elimination of food from the diet according to age, sex or type of IBD. No differences were observed in the elimination of dairy products, carbonated drinks or alcoholic beverages depending on the type of IBD, being more frequent the elimination of fibre in patients with UC (7/10 patients) than in CD. Regarding the role of their attending physician, 77.5% (86 patients) thought that nutrition was important for their doctor and/or nurse dedicated to IBD, although only 52.6% (61 patients) believed they had received enough information for their pathology. Conclusion The health professionals dedicated to IBD should increase our efforts to properly inform patients about nutritional aspects, since in our experience more than a half of patients avoid one or more foods (without scientific evidence to support it). Furthermore, only 52.6% consider that they receive sufficient information regarding this matter.

Background Vedolizumab is a monoclonal antibody that binds to an integrin resulting in gut-selective anti-inflammatory activity. It is indicated for the treatment of inflammatory bowel disease (IBD), both in Crohn’s disease (CD) and ulcerative colitis (UC), but no benefit has been proved on inflammatory joint disease. The aim of this study was to analyse the incidence of the debut of inflammatory joint disease and also analyse the prevalence of outbreak of the previously known joint disease in IBD patients during treatment with vedolizumab. Methods Descriptive observational study of a prospective cohort of IBD patients treated with vedolizumab. All patients met the following inclusion criteria: adults > 18 years, histological diagnosis of CD or UC and having received or being currently being treated with vedolizumab. Demographic, clinical and analytical information were obtained from the Hospital’s database from both Gastroenterology and Rheumatology clinical records. Results A total of 44 patients (25 with CD and 19 with UC) were included. Of these, most had been pretreated with anti-TNF (41 switchers and 3 patients näive to biological therapy). The mean age of the included patients was 50 ± 15.4 years with predominantly female (54%). The mean follow-up time of patients in this study was 26 ± 10 months. In total, 13 patients (30%) presented joint symptoms during treatment with vedolizumab (8 with EC and 9 with UC). Of these 13 patients, 3 already had previous diagnosis of inflammatory joint pathology (spondyloarthritis), 6 patients debuted with inflammatory joint symptoms during treatment with vedolizumab and 4 mechanical arthralgias. Of the 6 patients with debut of inflammatory profile symptoms, inflammatory pathology was confirmed in 5 patients (spondyloarthritis) and 1 patient presented osteomuscular mechanical pathology. A total of 11 patients with the diagnosed rheumatological disease (25%) were observed in this cohort. Conclusion The incidence of inflammatory joint pathology in IBD patients treated with vedolizumab is similar to the one described in other cohorts regardless of the treatment received. Suspension of anti-TNF treatment to switch to vedolizumab may be associated with outbreaks of rheumatic disease. This presents a new challenge in the therapeutic approach, being crucial a multidisciplinary approach.

Background: Data regarding the effectiveness of adalimumab (ADA) in the treatment of perianal fistula in patients with Crohn's disease (CD) naive to antitumor necrosis factor (TNF) therapy are scarce. Aim: To assess the effectiveness of ADA in the treatment of perianal fistulas in CD patients naive to anti-TNF therapy. Methods: A retrospective multicenter study was designed. The Fistula Drainage Assessment Index was used to assess the clinical response, and the Van Assche and Ng indexes to classify radiologic response (magnetic resonance imaging). Results: A total of 46 patients (83% women, 83% complex fistula) were included. At 6 months, 72% of patients responded to ADA (54% remission, 18% partial response) and at 12 months 49% responded (41% remission, 8% partial response). Among patients with complex fistula, the response rate was 66% at 6 months and 39% at 12 months. Nine patients escalated the ADA dose to 40mg weekly, 6 for partial response and 3 for absence of response. Thirty-three percent of these patients achieved remission after dose escalation. There was a good correlation between clinical and radiologic assessment of response (kappa = 0.68). In the multivariate analysis, complex fistula was the only predictor of a worse response (hazard ratio 0.083; 95% confidence interval, 0.0009-0.764; P = 0.028). Adverse effects were recorded in 11% of patients. Conclusions: ADA was effective for the treatment of perianal fistulas in CD patients naive to anti-TNF drugs. We found a good correlation between clinical and radiologic assessment of therapy response.

Despite the efficacy demonstrated by anti-TNF drugs in treating inflammatory bowel disease, there is a significant percentage of patients for whom the drugs fail or the response to the drugs is lost. The limitations in managing these patients and the increase in costs necessitate an individualised strategy to optimise their clinical management. Recent studies have noted the relationship between the clinical outcome and therapeutic adjustments based on monitoring anti-TNF levels and the presence of antibodies, taking into account other factors such as the type of disease and its severity. This study reviews the available information and proposes a clinical management algorithm to achieve a more efficient result.

Background: The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. Methods: In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54 weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. Results: Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's disease patients treated with IFX. AntiIFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3 nM). The threshold level of ATI in order to classify the immunogenicity of the patients was 10 nM. We observed that 24% (12/50) of IFX-treated patients developed ATI (>10 nM) during the observation period (54 weeks). Serum concentration of ATI higher than 10 nM dramatically increased the probability (OR = 51.1; 95% CI: 20.4-128.0; p < 0.0001) of presenting low levels of IFX (

Background & Aims: Therapies for perianal fistulas in patients with Crohn's disease are often ineffective in producing long-term healing. We performed a randomized placebo-controlled trial to determine the long-term efficacy and safety of a single local administration of allogeneic expanded adipose-derived stem cells (Cx601) in patients with Crohn's disease and perianal fistulas. Methods: We performed a double-blind study at 49 hospitals in Europe and Israel, comprising 212 patients with Crohn's disease and treatment-refractory, draining, complex perianal fistulas. Patients were randomly assigned (1:1) to groups given a single local injection of 120 million Cx601 cells or placebo (control), in addition to the standard of care. Efficacy endpoints evaluated in the modified intention-to-treat population (randomly assigned, treated, and with 1 or more post-baseline efficacy assessment) at week 52 included combined remission (closure of all treated external openings draining at baseline with absence of collections >2 cm, confirmed by magnetic resonance imaging) and clinical remission (absence of draining fistulas). Results: The study's primary endpoint, at week 24, was previously reported (combined remission in 51.5% of patients given Cx601 vs 35.6% of controls, for a difference of 15.8 percentage points; 97.5% confidence interval [CI] 0.5–31.2; P =.021). At week 52, a significantly greater proportion of patients given Cx601 achieved combined remission (56.3%) vs controls (38.6%) (a difference of 17.7 percentage points; 95% CI 4.2–31.2; P =.010), and clinical remission (59.2% vs 41.6% of controls, for a difference of 17.6 percentage points; 95% CI 4.1–31.1; P =.013). Safety was maintained throughout week 52; adverse events occurred in 76.7% of patients in the Cx601 group and 72.5% of patients in the control group. Conclusion: In a phase 3 trial of patients with Crohn's disease and treatment-refractory complex perianal fistulas, we found Cx601 to be safe and effective in closing external openings, compared with placebo, after 1 year. ClinicalTrials.gov no: NCT01541579.

Background and Aims The aims of this study were to determine the prevalence of fatigue in patients with inflammatory bowel disease [IBD], to identify the factors associated with fatigue and its severity, to assess the impact of fatigue on quality of life [QoL], and to evaluate the relationship between fatigue and sleep disorders. Methods This was a prospective multicentre study conducted at 22 Spanish centres. Consecutive patients followed at IBD Units were included. Fatigue was evaluated with the Fatigue Severity Scale [FSS] and the Fatigue Impact Scale [FIS]. Quality of life and sleep quality were assessed using the IBD Questionnaire-Short Form [IBDQ-9] and the Pittsburgh Sleep Quality Index [PSQI], respectively. Results A total of 544 consecutive adult IBD patients were included [50% women, mean age 44 years, 61% Crohn’s disease]. The prevalence of fatigue was 41% (95% confidence interval [CI] = 37–45%). The variables associated with an increased risk of fatigue were: anxiety [OR = 2.5, 95% CI = 1.6–3.7], depression [OR = 2.4, 95% CI = 1.4–3.8], presence of extraintestinal manifestations [EIMs] [OR = 1.7, 95% CI = 1.1–2.6], and treatment with systemic steroids [OR = 2.8, 95% CI = 1.4–5.7]. The presence of EIMs [regression coefficient, RC = 8.2, 95% CI = 2.3–14.2], anxiety [RC = 25.8, 95% CI = 20.0–31.5], depression [RC = 30.6, 95% CI = 24.3–37.0], and sleep disturbances [RC = 15.0, 95% CI = 9.3–20.8] were associated with severity of fatigue. Patients with fatigue had a significantly decreased IBDQ-9 score [p < 0.001]. Conclusions The prevalence of fatigue in IBD patients is remarkably high and has a negative impact on QoL. Therapy with systemic steroids is associated with an increased risk of fatigue. The severity of fatigue is associated with anxiety, depression, sleep disorders, and the presence of EIMs. Fatigue was not associated with anaemia, disease activity or anti-TNF therapy.