The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan–Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8–1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5–4.3)). In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.

Background and objective: Probiotics show promise in inflammatory bowel disease (IBD), yet knowledge gaps persist. We performed an overview of systematic reviews and an updated metanalysis of randomized controlled trials (RCT) assessing the effect of probiotics on Crohn's disease (CD) and ulcerative colitis (UC). Methods: MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched up to September 2023. Primary outcomes were clinical remission and recurrence; secondary outcomes included endoscopic response and remission, and adverse events. We calculated odds ratios (OR) using a random‐effects model in R. The quality of systematic reviews was assessed using the AMSTAR‐2; the trials' risk of bias was evaluated using the Cochrane Collaboration tool. Evidence certainty was rated using the GRADE framework. Results: Out of 2613 results, 67 studies (22 systematic reviews and 45 RCTs) met the eligibility criteria. In the updated meta‐analysis, the OR for clinical remission in UC and CD was 2.00 (95% CI 1.28–3.11) and 1.61 (95% CI 0.21–12.50), respectively. The subgroup analysis suggested that combining 5‐ASA and probiotics may be beneficial for inducing remission in mild‐to‐moderate UC (OR 2.35, 95% CI 1.29–4.28). Probiotics decreased the odds of recurrence in relapsing pouchitis (OR 0.03, 95% CI 0.00–0.25) and trended toward reducing clinical recurrence in inactive UC (OR 0.65, 95% CI 0.42–1.01). No protective effect against recurrence was identified for CD. Multi‐strain formulations appear superior in achieving remission and preventing recurrence in UC. The use of probiotics was not associated with better endoscopic outcomes. Adverse events were similar to control. However, the overall certainty of evidence was low. Conclusion: Probiotics, particularly multi‐strain formulations, appear efficacious for the induction of clinical remission and the prevention of relapse in UC patients as well as for relapsing pouchitis. Notwithstanding, no significant effect was identified for CD. The favorable safety profile of probiotics was also highlighted.

Inflammatory bowel disease [IBD] is a complex chronic disorder with no clear aetiology and no known cure. Despite recent advances in overall disease management and improved therapeutics, patients with IBD still experience a substantial burden. Furthermore, as the incidence continues to increase in developing areas of the world, it is expected that the burden of IBD to society will increase and exert tremendous pressure on health care systems worldwide. Therefore, new strategies to prevent the global increase of IBD are urgently required. Data are being progressively acquired on the period preceding disease diagnosis, which support the concept that IBD has a preclinical period that may reveal the triggers of disease and may be amenable to early intervention. Having a better knowledge of this preclinical period will increase the potential not only for improved understanding of disease pathogenesis and improved therapeutics, but also for disease prediction and prevention.

Background and Aims: Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies.Methods: PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool.Results: In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50–139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7–19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9–5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1–9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39–53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC.Conclusions: PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.

Background: There is limited evidence on the effectiveness of biological therapy in stricturing complications in patients with Crohn’s disease.Aim: The study aims to determine the effectiveness of anti‐tumor necrosis factor (TNF) agents in Crohn’s disease complicated with symptomatic strictures.Methods: In this multicentric and retrospective study, we included adult patients with symptomatic stricturing Crohn’s disease receiving their first anti‐TNF therapy, with no previous history of biological, endoscopic or surgical therapy. The effectiveness of the anti‐TNF agent was defined as a composite outcome combining steroid‐free drug persistence with no use of new biologics or immunomodulators, hospital admission, surgery or endoscopic therapy during follow‐up.Results: Overall, 262 patients with Crohn’s disease were included (53% male; median disease duration, 35 months, 15% active smokers), who received either infliximab (N = 141, 54%) or adalimumab (N = 121, 46%). The treatment was effective in 87% and 73% of patients after 6 and 12 months, respectively, and continued to be effective in 26% after a median follow‐up of 40 months (IQR, 19–85). Nonetheless, 15% and 21% of individuals required surgery after 1 and 2 years, respectively, with an overall surgery rate of 32%. Postoperative complications were identified in 15% of patients, with surgical site infection as the most common. Starting anti‐TNF therapy in the first 18 months after the diagnosis of Crohn’s disease or the identification of stricturing complications was associated with a higher effectiveness (HR 1.62, 95% CI 1.18–2.22; and HR 1.55, 95% CI 1.1–2.23; respectively). Younger age, lower albumin levels, strictures located in the descending colon, concomitant aminosalicylates use or presence of lymphadenopathy were associated with lower effectiveness.Conclusions: Anti‐TNF agents are effective in approximately a quarter of patients with Crohn’s disease and symptomatic intestinal strictures, and 68% of patients are free of surgery after a median of 40 months of follow‐up. Early treatment and some potential predictors of response were associated with treatment success in this setting.