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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.

Pouchitis is a frequent complication in ulcerative colitis patients after proctocolectomy with ileal pouch-anal anastomosis. It is an unspecific inflammation of the pouch with unknown aetiology. First-line treatment for acute and chronic pouchitis is antibiotics. Some cases of severe chronic refractory pouchitis may benefit from biological treatment. Anti-tumour necrosis factor should be recommended as the first option, leaving the new biologicals for multirefractory patients. Permanent ileostomy may be an option in severe cases, after failure of medical treatment. Prophylaxis therapy with a probiotic mixture is recommended after the first episode of pouchitis, whereas it is not clear whether probiotics are useful for all patients after surgery. Here, we present a case report and review the treatment options in different forms of pouchitis.

Background/Objectives The epidemiology of exocrine pancreatic insufficiency (EPI) after acute pancreatitis (AP) is uncertain. We sought to determine the prevalence, progression, etiology and pancreatic enzyme replacement therapy (PERT) requirements for EPI during follow-up of AP by systematic review and meta-analysis. Methods Scopus, Medline and Embase were searched for prospective observational studies or randomized clinical trials (RCTs) of PERT reporting EPI during the first admission (between the start of oral refeeding and before discharge) or follow-up (≥ 1 month of discharge) for AP in adults. EPI was diagnosed by direct and/or indirect laboratory exocrine pancreatic function tests. Results Quantitative data were analyzed from 370 patients studied during admission (10 studies) and 1795 patients during follow-up (39 studies). The pooled prevalence of EPI during admission was 62% (95% confidence interval: 39–82%), decreasing significantly during follow-up to 35% (27–43%; risk difference: − 0.34, − 0.53 to − 0.14). There was a two-fold increase in the prevalence of EPI with severe compared with mild AP, and it was higher in patients with pancreatic necrosis and those with an alcohol etiology. The prevalence decreased during recovery, but persisted in a third of patients. There was no statistically significant difference between EPI and new-onset pre-diabetes/diabetes (risk difference: 0.8, 0.7–1.1, P = 0.33) in studies reporting both. Sensitivity analysis showed fecal elastase-1 assay detected significantly fewer patients with EPI than other tests. Conclusions The prevalence of EPI during admission and follow-up is substantial in patients with a first attack of AP. Unanswered questions remain about the way this is managed, and further RCTs are indicated. Electronic supplementary material The online version of this article (10.1007/s10620-019-05568-9) contains supplementary material, which is available to authorized users.

Background It has been suggested that biologic therapy may increase the risk of postoperative complications in inflammatory bowel disease (IBD), but the evidence is scarce. Our aim was to evaluate whether the treatment with anti-TNF agents, ustekinumab or vedolizumab increase the risk of complications after surgery. Methods IBD patients undergoing intra-abdominal surgery between 1st January 2009 and 31st December of 2019 were retrospectively selected. Data collection included clinical characteristic of IBD, biochemical parameters and surgical aspects. Postoperative complications (PC) were defined as those occurring within 30 days after surgery. Exposed cohort (EC): Patients who received the last dose of the biologic within 3 months before surgery. Non-exposed cohort (NEC): Patients who did not receive biologic treatment within 3 moths prior to surgery. Predictive factors for PC and for infections were identified by logistic regression analyses. A genetic matching score was performed to balance the clinical characteristics of both groups. Results A total of 1,535 surgeries performed in 37 centres were included: 81% in Crohn’s disease, 18% in ulcerative colitis and 1% in unclassified-IBD patients. A total of 711 surgeries (46.3%) had been exposed to biologics (583 under anti-TNF therapy, 58 under vedolizumab and 69 under ustekinumab) and 824 surgeries (53.7%) the NEC. PC were reported in 38% (n=267) of patients in the exposed cohort and in 34% (n=280) of patients in the non-exposed one (p=0.15), including dehiscence, infection, obstruction, ileus, bleeding, thrombosis, fistula and evisceration. The most frequent complications were infections (48% of all the cases). A 30-day hospital readmission was needed in 7% (n=110) of the patients, and 2% (n=29) required a new surgery with no differences (p>0.05). Multivariate analysis for PC and infections is presented in table 1. The frequencies of PC for each biologic in the univariate analysis are represented in figure 1. No specific treatment was associated to PC or infections in multivariate analysis. Conclusion Preoperative administration of biological therapy does not seem to be a risk factor for overall PC, although it may be for postoperative infections.

Background The urinary metabolome of patients with Crohn’s disease (CD) differs significantly from healthy subjects and, among other features, reflects the specific gut dysbiosis affecting these patients. However, most of the studies included established and treated CD patients. Our aim was to characterize the urinary metabolome of onset and treatment-naïve CD patients and to identify the metabolic profile related to the different CD clinical classifications. Methods Patients newly diagnosed with CD (n=131) were prospectively included. Control healthy subjects (HC, n=338) were recruited among the general population and matched for sex, age and BMI to the IBD subjects. Fasting urine was obtained before starting any treatment. Metabolomic analysis was performed by proton nuclear magnetic resonance (1H NMR). We performed a comparative assessment of the urinary metabolome profile using a linear regression model for each metabolite, including sex, age, BMI, and smoking habit as covariates to control for confounding. The different subgroup comparisons within CD were made as follows: (1) CD; (2) CD location (Montreal Classification): L1 (ileal) + L4 (ileal and upper-intestinal), L2 (colonic) and L3 (ileocolonic); (3) endoscopic CD activity: 0, 1, 2 and 3; and (4) CD phenotype: B1 (inflammatory), B2 (stricturing) and B3 (penetrating), versus HC. In addition, data analysis was carried out using partial least squares-discriminate analysis (PLS-DA) to determine class membership based on distinct metabolomic profile. Results The primary characteristics of the CD patients and HC are shown in Table 1. Several metabolites were identified to be differently abundant in each group (Table 2). These metabolites are involved in relevant processes related to energy and aminoacids metabolism, and also include gut-derived metabolites. The PLS-DA model separated patients within the different clinical subgroups (Figures 1–4). Figures 1–4(b) show the main metabolites involved in each group separation. Many of these metabolites are in accordance with the differential metabolites obtained using the univariate analysis (Table 2), showing the potential of this approach to group CD patients and to identify potential biomarkers. Conclusion Analysis of urinary metabolites can help to understand the etiopathological mechanisms in CD. It has the potential to provide a non-invasive means of diagnosing CD, and can differentiate between CD clinical expressions.

Background Lack of adherence in patients with inflammatory bowel disease (IBD) is a relevant problem in our clinical practice. Non-adherence to anti-TNF increases healthcare costs. The aim of this study was both to measure adherence and also to study the factors and consequences related to non-adherence in patients with IBD under maintenance treatment with infliximab (IFX). Methods A prospective, observational cohort study was designed and patients with IBD under treatment with IFX were consecutively included. Adherence was measured with pharmacy refills and Morisky Medication Adherence Scale-8 (MMAS-8). Patients were systematically asked about adherence and the mean displacement days, the accumulated delay, the mean delay and the medication possession ratio (MPR) were calculated. MPR was calculated by dividing the number of days supplied within the refill interval by the number of days in the actual refill interval over 24 months. Potencial risk factors for non-adherence were evaluated: age, gender, disease duration, site of disease, behaviour of Crohn’s disease (CD), smoking status, educational level, marital status, type of housing, extraintestinal manifestations, previous surgery, concomitant treatments, anxiety and depression. Relapse was defined as a Harvey Bradshaw score > 4 in CD and a partial Mayo > 2 in ulcerative colitis (UC). The Mann-Whitney Wilcoxon U Test was used to distinguish the intergroup differences. Correlations were evaluated with Spearman rank correlation coefficients. Results Ninety patients with mean age 46 years (range: 22–85) were included. 49 (54.4%) were women and 63 (70%) had CD. Anxiety occurred in 38.9% of patients and depression in 78.9%. Three quarters of the patients were in clinical remission at inclusion. After 24 months of follow-up, 82 (91.1%) had delayed some dose of treatment, 35 (38.9%) had delayed on at least 7 days some dose of treatment, and 11 (12.2%) had not received some of the scheduled doses. The MPR was 87% (range 46–100). Lack of adherence was related to loss of response to IFX in CD (p = 0.035), but not in UC (p=0.078). In UC, lack of adherence was related with anxiety (p=0.046). The Spearman’s correlation between older age and non-adherence was 0.53 (p=0.006) in UC and 0.1 (p=0.308) in CD. Conclusion Lack of adherence is related to loss of response to IFX in CD. Non-adherence to IFX is high and strongly associated with age in UC. Older patients with UC are more prone to lack of adherence.

Background Biological drugs are being increasingly used for the treatment of inflammatory bowel diseases (IBD) in elderly patients. Despite the particular characteristics of this population subgroup, the efficacy and safety of these treatments in real clinical practice is poorly evaluated. Methods Retrospective and multicenter study of GETECCU, carried out in 28 Spanish hospitals. Patients with IBD who started biological treatment (Infliximab, Adalimumab, Golimumab, Ustekinumab or Vedolizumab) aged 65 years or older were included. Efficacy (clinical- at the criteria of the responsible physician-, biochemical and endoscopic) was assessed at 12-14 weeks and at 52 weeks of treatment. Adverse effects such as tumors or serious infections were also recorded. Results A total of 570 patients were included, baseline characteristics are shown in Table 1. Biologics used were: Infliximab (214, 37.5%), Adalimumab (167, 29.3%), Golimumab (16, 2.8%), Ustekinumab (73, 12.8%) and Vedolizumab (100, 17.5%). After 12-14 weeks of treatment, in 38.7% (220) of the cases clinical remission had been achieved and in 47.7% (270) there was clinical response without remission. However, 80 patients (13.9%) had no response, resulting in treatment discontinuation due to primary failure. At week 52, only 379 patients (66.5%) continued on biological treatment: 216 (57%) were in clinical remission (216, 57.0%) while 129 (34%) had response without remission and 34 (9%)had no response. In addition, 119 patients (21%) had an endoscopic study performed: 47 (39,5%) presented with endoscopic remission, 38 (31,9%) with mild activity, 28 (23,5%) with moderate activity and 6, (5.1%) with severe activity. At the end of the follow-up, only 60% of the patients continued on biological treatment, being the reason for withdraw lack of efficacy or due to the report of adverse side effects. Regarding treatment safety in this population, 12.1% (68 patients) suffered an infectious complication with a microbiological diagnosis, requiring hospitalization in 62.1% of the cases. In addition, 39 patients (6.9%) were diagnosed with a tumor until the end of the follow-up, noting that 34.2% of the cases continued on biological therapy after the diagnosis. Likewise, in 25 patients (36.8%) this infection forced discontinuation of biological treatment. Finally, 10 patients stopped biological treatment due to a serious adverse reaction to it Conclusion Response rates to biological treatment in elderly patients are similar to those described in the general population, with approximately one third of failures happening during the first year. However, a remarkable proportion of patients developed a serious adverse effect that could be related to treatment

Inflammatory bowel diseases (IBDs) are chronic disabling conditions, characterized by an unpredictable course with flare-ups and periods of remission, that frequently affect young people and require lifelong medical follow-up and treatment. For years, the main endpoints of IBD treatment had been clinical remission and response, followed by biomarker normalization and mucosal healing. In the last decades, different therapies have been proved to be effective to treat IBD and the use of patient reported outcome (PRO) have become more relevant. Therefore, health-related quality of life (HRQoL) that has been defined as the value assigned to the duration of life influenced by physical and mental health, has been suggested as an important endpoint for IBD management since multiple studies have shown that IBD impairs it, both physically and psychologically. Thus, HRQoL has been included as an outcome in numerous studies evaluating different IBD therapies, both clinical trials and real-life studies. It has been assessed by using both generic and specific disease tools, and most treatments used in clinical practice have been demonstrated to improve HRQoL. The relevance of HRQoL as an endpoint for new drugs is going to increase and its management and improvement will also improve the prognosis of IBD patients.

Background The novel coronavirus emerged in 2019 in Wuhan has caused a global pandemic of coronavirus disease (COVID-19). Immune-mediated diseases (IMID), as inflammatory arthritis or inflammatory bowel disease (IBD), have some special implications due to their pathogenesis and treatments. Some treatments employed in IMID are now being used in the treatment of severe COVID-19. There still exists controversy about IMID behavior and its complications. Our aim was to assess COVID-19 severity in IMID patients and its prognosis predictors. Methods An observational retrospective multicenter study was performed in two Spanish Hospitals (University Clinical Hospital in Santiago de Compostela and Gregorio Marañón Hospital). Patients were selected if they were diagnosed of an IMID (rheumatoid arthritis, psoriatic arthritis, espondyloarthritis, ulcerative colitis and Crohn’s disease) and had COVID-19 infection between February and April 2020. Demographic, clinical, analytical and treatment data were collected. Stata 15.1 was used to perform statistical analysis. Results 91 patients were included. 55 suffered from a rheumatic disease and 36 suffered IBD. Univariable analysis reached age, comorbidity, female gender, flu vaccine, arthropathy, basal csDMARD, pneumonia and basal CRP as potential predictors of non-severe (absence of death, respiratory insufficiency, intensive care unit admission or sepsis) COVID-19 disease (p < 0.2). After multivariable analysis, only female gender (OR 4.60 [CI95% 1.00, 21.2] p=0.050), lower age (OR 0.94 [CI95% 0.88, 1.00] p=0.042) and lower basal levels of CRP (OR 0.87 [CI95% 0.77, 0.97] p=0.010) were predictors for non-severe disease (p < 0.005). Mean time of healing (symptoms solved in outpatient and hospital discharge in admitted) from COVID-19 was 13.8 days (SD 16.3). Univariable analysis showed arthropathy, COVID-19 symptomatic and basal GC dose as potential predictors of higher time-to-healing from COVID-19 disease (p < 0.2). After multivariable analysis, only lower GC basal dose predicts higher time-to-healing (OR -1.83 [CI95% -2.81, -0.84] p=0.001).11 patients deceased because of SARS-CoV-2 infection. Univariable analysis reached age, basal csDMARD, pneumonia and basal CRP as potential predictors of COVID-19 mortality (p < 0.2). After multivariable analysis, only higher age was a predictor for mortality (OR 1.14 [CI95% 1.04,1.25] p=0.006). Conclusion IMID patients showed similar predictors of mortality than general population involving COVID-19. Immune-modulating agents did not seem to overshadow the prognosis of COVID-19 infection. Female gender, lower age and lower basal CRP is associated with mild COVID-19 disease as well higher age points out the worst prognosis. Even that, each case should be individualized.

Background The rate of H. pylori resistance to different antibiotics is increasing and determines the selection of eradication therapy. The aim of this study was to determine the resistance patterns of H. pylori strains in our area. Methods Biopsies from gastric corpus for microbiological culture and antibiotic resistance were obtained in patients undergoing upper gastrointestinal endoscopy for dyspepsia. Selective Agar Pylori for isolation of the bacteria and Agar Mueller-Hinton supplemented with blood to test the sensitivity to antibiotics were used. Presence of H. pylori was confirmed using direct observation with phase-contrast microscopy and/or smears stained with acridine orange. In vitro bacterial susceptibility to amoxicillin, clarithromycin, rifampicin, tetracycline, metronidazole, and levofloxacin was tested using diffusion MIC test strips. Minimum inhibitory concentration values were determined based on the 6th version of the EUCAST (European Committee on Antimicrobial Susceptibility Testing) Clinical Breakpoint (2016). Results Two hundred and seventeen patients were included (58.1% female, median age 64 years, range 25-92). H. pylori was identified in 108 patients (49.8%); culture and antibiogram were completed in 77 of them (71.3% of H. pylori-positive patients). The resistance rates were as follows: levofloxacin 38.7%, rifampicin 33.3%, metronidazole 27% and clarithromycin 22.4%. No case of amoxicillin or tetracycline resistance was identified. Dual clarithromycin-metronidazole resistance was observed in 10% of strains, whereas multiple drug-resistant was observed in 14.2%. Conclusions Resistance rate of H. pylori to antibiotics is high in the northwest of Spain. The high resistance to levofloxacin and clarithromycin advises against their wide empirical use of these antibiotics in eradication regimens.

Objective The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP. Design Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined. Results A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, p 2 =89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I 2 =86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking. Conclusions PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition.

Background Concomitant quadruple (CQT) or bismuth-containing quadruple therapy (BQT) is recommended as first-line treatment for Helicobacter pylori infection depending on antibiotic resistance. Aim To compare the efficacy, safety, and compliance of CQT and BQT as first-line therapy for H. pylori eradication in real clinical practice in an area of high resistance to clarithromycin. Methods A prospective, open, comparative cross-sectional study including dyspeptic patients >18 years with H. pylori infection and with no previous eradication treatment was performed. CQT (omeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1 g + metronidazole 500 mg, all given twice daily, for 14 days) or BQT (omeprazole 20 mg twice daily + 3 capsules of Pylera® 4 times a day, for 10 days) was prescribed at the discretion of the prescribing physician. Eradication was tested by 13 C-urea breath test. Efficacy was assessed by intention-to-treat (ITT) and per-protocol (PP) analyses. Results One hundred and four consecutive patients were included (64.4% female, age 52.9 years). Fifty patients received CQT and 54 BQT. Eradication rate was similar with both therapies at the PP (CQT 97.9%, 95% CI: 93.9-100 vs BQT 96.2%, 95% CI: 90.9-100, P = 0.605) and ITT analyses (CQT 98.0%, 95% CI: 94-100 vs BQT 94.4%, 95% CI: 88.1-100, P = 0.346). The rate of adverse events was also similar with CQT (56%) and BQT (46.3%). One patient in each group discontinued the treatment due to significant adverse events. Conclusion The use of CQT and BQT as first-line treatment against H. pylori is similarly effective and safe strategy in an area of high clarithromycin resistance.