The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn’s disease and ulcerative colitis patients, respectively. In both Crohn’s disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01–1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07–3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27–2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13–2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09–2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn’s disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51–0.87) and age (HR=0.98; 95% CI=0.97–0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Postoperative recurrence of Crohn’s disease [POR-CD] is almost certain if no prophylaxis is administered. Evidence for optimal treatment is lacking. Our aim was to compare the efficacy of adalimumab [ADA] and azathioprine [AZA] in this setting. We performed a phase 3, 52-week, multicentre, randomised, superiority study [APPRECIA], in which patients with ileocolonic resection were randomised either to ADA 160-80-40 mg subcutaneously [SC] or AZA 2.5 mg/kg/day, both associated with metronidazole. The primary endpoint was endoscopic recurrence at 1 year [Rutgeerts i2b, i3, i4], as evaluated by a blinded central reader. We recruited 91 patients [median age 35.0 years, disease duration 6.0 years, 23.8% smokers, 7.1% previous resections]. The study drugs were administered to 84 patients. Treatment was discontinued owing to adverse events in 11 patients [13.1%]. Discontinuation was significantly less frequent in the ADA [4.4%] than in the AZA group [23.2%] (dif.: 18.6% [95% CI 4.1–33.2], p = 0.011). According to the intention-to-treat analysis, therapy failed in 23/39 patients in the AZA group [59%] and 19/45 patients in the ADA group [42.2%] [p = 0.12]. In the per-protocol analysis [61 patients with centrally evaluable images], recurrence was recorded in 8/24 [33.3%] patients in the AZA and 11/37 [29.7%] in the ADA group [p = 0.76]. No statistically significant differences between the groups were found for recurrence in magnetic resonance images, biological markers of activity, surgical procedures, or hospital admissions. ADA has not demonstrated a better efficacy than AZA [both associated with metronidazole] for prophylaxis of POR-CD in an unselected population, although tolerance to ADA is significantly better. ClinicalTrials.gov NCT01564823.

Beclometasone dipropionate (BDP) is a relatively new topically acting oral steroid to treat mild to moderately active ulcerative colitis (UC). We estimate that 20,000 patients have received oral BDP in Spain in the last two years. Our aim was to evaluate the efficacy and safety of oral BDP in clinical practice.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract due, at least partially, to an aberrant and excessive mucosal immune response to gut bacteria in genetically-predisposed individuals under certain environmental factors. The incidence of IBD is rising in western and newly industrialized countries, paralleling the increase of westernized dietary patterns, through new antigens, epithelial function and permeability, epigenetic me chanisms (e.g., DNA methylation), and alteration of the gut microbiome. Alteration in the composition and functionality of the gut microbiome (including bacteria, viruses and fungi) seems to be a nuclear pathogenic factor. The microbiome itself is dynamic, and the changes in food quality, dietary habits, living conditions and hygiene of these western societies, could interact in a complex manner as modulators of dysbiosis, thereby influencing the activation of immune cells’ promoting inflammation. The microbiome produces diverse small molecules via several metabolic ways, with the fiber-derived short-chain fatty acids (i.e., butyrate) as main elements and having anti-inflammatory effects. These metabolites and some micronutrients of the diet (i.e., vitamins, folic acid, beta carotene and trace elements) are regulators of innate and adaptive intestinal immune homeostasis. An excessive and unhealthy consumption of sugar, animal fat and a low-vegetable and -fiber diet are risk factors for IBD appearance. Fur thermore, metabolism of nutrients in intestinal epithelium and in gut microbiota is altered by inflammation, changing the demand for nutrients needed for homeostasis. This role of food and a reduced gut microbial diversity in causing IBD might also have a prophylactic or therapeutic role for IBD. The relationship between dietary intake, symptoms, and bowel inflammation could lead to dietary and lifestyle recommendations, including diets with abundant fruits, vegetables, olive oil and oily fish, which have anti-inflammatory effects and could prevent dysbiosis and IBD. Dietary modulation and appropriate exclusion diets might be a new complementary management for treatment at disease flares and in refractory patients, even reducing complications, hospitalizations and surgery, through modifying the luminal intestinal environment.

Background and Aims: Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation. Methods: Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses. Results: A total of 137 Crohn’s disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn’s disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters. Conclusions: This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.