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Vitamin D deficiency has been recognized as an environmental risk factor for Crohn’s disease since the early 80s. Initially, this finding was correlated with metabolic bone disease. Low serum 25-hydroxyvitamin D levels have been repeatedly reported in inflammatory bowel diseases together with a relationship between vitamin D status and disease activity. Subsequently, low serum vitamin D levels have been reported in various immune-related diseases pointing to an immunoregulatory role. Indeed, vitamin D and its receptor (VDR) are known to interact with different players of the immune homeostasis by controlling cell proliferation, antigen receptor signalling, and intestinal barrier function. Moreover, 1,25-dihydroxyvitamin D is implicated in NOD2-mediated expression of defensin-β2, the latter known to play a crucial role in the pathogenesis of Crohn’s disease (IBD1 gene), and several genetic variants of the vitamin D receptor have been identified as Crohn’s disease candidate susceptibility genes. From animal models we have learned that deletion of the VDR gene was associated with a more severe disease. There is a growing body of evidence concerning the therapeutic role of vitamin D/synthetic vitamin D receptor agonists in clinical and experimental models of inflammatory bowel disease far beyond the role of calcium homeostasis and bone metabolism.

We performed a systematic review and meta-analysis of all the available evidence comparing efficacy and safety of oral prolonged released beclomethasone dipropionate (BDP) to active oral controls in patients with mild-to-moderate ulcerative colitis (UC). A subgroup-analysis compared the effectiveness of BDP and 5-ASA. Literature research was performed in different databases, as well as manual search to identify abstracts from international meetings with data not included in extensive publications. Experts in the field and companies involved in BDP development and manufacture were contacted to identify unpublished studies used for registration purposes. Dichotomous data were pooled to obtain odds ratio meta-analysis. Five randomized controlled trials that compared oral BDP 5mg/day vs. all oral active controls in treating UC were identified as eligible. Efficacy and safety have been addressed after 4-week treatment period. One study evaluated efficacy and safety of BDP vs. prednisone and 4 of BDP vs. 5-ASA. Treatment with oral BDP 5 mg/day induces a significant better clinical response compared to oral 5-ASA (OR 1.86, 95% CI = 1.23-2.82, P = 0.003). The effect is detectable even when the comparison to prednisone is added (OR 1.41, 95% CI = 1.03-1.93, P = 0.03). Data on remission indicate that the potential clinical efficacy of BDP may be better than 5-ASA (OR 1.55, 95% CI = 1.00-2.40, P = 0.05). This difference is lost when the comparison with prednisone is added (OR 1.30, 95% CI = 0.76-2.23, P = 0.34). The safety analysis showed no differences between BDP and 5-ASA (OR 0.55, 95% CI = 0.24-1.27, P = 0.16). The lack of difference is maintained even when the study with prednisone is added (OR 0.67, 95% CI = 0.44-1.01, P = 0.06). However, the trend of difference is clear and indicates a more favourable safety profile of BDP compared to 5-ASA and PD. Oral prolonged release BDP showed a superior efficacy vs. oral 5-ASA in inducing clinical improvement of mild-to-moderate UC with a similar safety profile.

Abstract Background Data from the first wave of the coronavirus disease 2019 (COVID-19) pandemic suggested that patients with inflammatory bowel disease (IBD) are not at higher risk of being infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population and that a worse prognosis is not associated with immunomodulatory drugs, with the possible exception of systemic steroids. Methods This retrospective, observational study included consecutive IBD patients from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) cohort who had a SARS-CoV-2 infection diagnosis (polymerase chain reaction–confirmed presence of the viral genome in a nasopharyngeal swab) during the second COVID-19 pandemic wave (September 2020 to December 2020). Data regarding demographics, IBD features and treatments, and comorbidities were analyzed in correlation with COVID-19 clinical outcomes. Results Data on 122 patients (mean age, 43.9 ± 16.7 years; males, 50.0%; Crohn’s disease, 62.3%; ulcerative colitis, 37.7%) were reported. Twelve patients developed COVID-19-related pneumonia (9.8%), 4 (3.3%) required respiratory assistance (nonmechanical ventilation or orotracheal intubation), and 4 died (case fatality rate, 3.3%). In a multivariable analysis, age (odds ratio [OR], 1.034; 95% CI, 1.006–1.147; P = .032) and severe IBD activity (OR, 13.465; 95% CI, 1.104–164.182; P = .042) were independent predictors of COVID-19-related pneumonia, while severe IBD activity (OR, 15.359; 95% CI, 1.320–178.677; P = .030) was the only independent predictor of severe COVID-19, a composite endpoint defined as the need for respiratory assistance or death. A trend towards a protective role of tumor necrosis factor α inhibitors on pneumonia development was reported (P = .076). Conclusions In this cohort of patients with IBD and SARS-CoV-2 infection, severe IBD activity was the only independent risk factor for severe COVID-19. Lay Summary This retrospective, observational study on patients with inflammatory bowel disease and severe acute respiratory syndrome coronavirus 2 infection showed that severe inflammatory bowel disease activity was the only independent risk factor for severe coronavirus disease 2019.

With the introduction of more and more monoclonal antibodies selectively targeting various mediators of the immune system, together with Janus-Kinase (JAK)-inhibitors with variable affinities towards different JAK subtypes, the available therapeutic options for the treatment of inflammatory bowel diseases (IBD) have undergone an acceleration in the last five years. On the other hand, the prevalence of IBD patients over 65-years-old is steadily increasing, and, with this, there is a large population of patients that presents more comorbidities, polypharmacy, and, more frequently, frailty compared to younger patients, exposing them to potentially major risks for adverse events deriving from newer therapies, e.g., infections, cardiovascular risks, and malignancies. Unfortunately, pivotal trials for the commercialization of new therapies rarely include older IBD patients, and those with serious comorbidities are virtually excluded. In the present review, we focus on existing literature from pivotal trials and real-world studies, analyzing data on efficacy/effectiveness and safety of newer therapies in older IBD patients with special emphasis on comorbidities and frailty, two distinct but intercorrelated aspects of the older population since age by itself seems to be of minor importance.

Glucose‐6‐phosphate‐dehydrogenase (G6PD) deficiency is a heterogenous disorder that may lead to severe hemolytic events with the ingestion of fava beans and exposure to certain drugs. We report the first case of a 65‐year‐old male with Crohn's disease who developed a hemolytic crisis leading to hospitalization shortly after commencement of upadacitinib. An autoimmune condition was excluded but, as his family history was a positive for G6PD deficiency, very low levels of erythrocyte G6PD were detected. Upadacitinib was immediately discontinued with subsequent resolution of hemolysis. This case highlights the importance of rigorous pharmacological surveillance and suggests the need for further studies to clarify the pathogenetic mechanisms underlying this adverse reaction.

Post-marketing surveillance is essential to evaluate the risk/benefit profile of drugs; however, pharmacovigilance studies comparing persistence and safety of biologic therapies in patients with inflammatory bowel disease (IBD) are scant. The aim of this study was to prospectively investigate persistence together with safety profiles of biologics in a cohort of patients diagnosed with Crohn’s Disease (CD) or ulcerative colitis (UC) followed by the IBD unit of Messina and treated with infliximab (IFX), adalimumab (ADA), golimumab (GOL), vedolizumab (VED), and ustekinumab (UST) from 2017 through 2021. Descriptive and treatment persistence analyses with predictors for discontinuation and occurrence of adverse drug reactions (ADRs) were performed. A total of 675 IBD patients were enrolled. A higher persistence rate was noted for UST and ADA in the first year (83.8% and 83.1%, respectively) and for IFX in the fifth year of treatment (58.1%). GOL, VED, and UST—all used as second/third-line therapies—seemed to have a higher risk of non-persistence than IFX (in order HR: 2.19; CI 95%: 1.33–3.61, 1.45; 1.04–2.04, 2.25; 1.25–4.07) as well as switchers and those who had at least one ADR (18.1; 13.22–24.68 and 1.55; 1.20–1.99, respectively). The reported ADRs, which were generally mild–moderate, were largely known. However, real-world data should be implemented to further study undetected safety concerns, including risk of malignancy.

New therapeutic approaches for ulcerative colitis (UC) are now available, but there is still no robust evidence for predictors of poor outcomes. We aimed to evaluate the factors associated with a chronic active UC disease course. Data of all UC outpatients followed for at least 3 years after diagnosis between 2005 and 2018 were retrospectively collected. The primary aim was to identify risk factors for chronic active disease 3 years after diagnosis. Moreover, the following variables were investigated: proximal disease extension or disease regression, proctocolectomy, early use of biologics (BIO) or immunomodulators (IMM), hospitalization, colorectal cancer, and adherence. We defined adherence as both, taking the prescribed therapy and constancy in scheduled follow-up visits. A total of 345 UC patients followed for a median period of 82 months were included. Patients with extensive colitis at diagnosis had a higher rate of chronic active disease 3 years after diagnosis (p<0.012) together with a higher rate of surgery (p<0.001) at maximum follow-up. Patients with pancolitis showed significant disease regression over time (51%) without differences in treatment. The only factor associated with chronic active disease was non-adherence (p < 0.03; OR 0.49, 95% CI: 0.26-0.95). Adherent patients developed chronic active disease (p<0.025) less frequently but did receive more frequent IMM (p<0.045) or BIO (p<0.009) therapy. Patients diagnosed with pancolitis were more likely to have chronic active disease and to undergo colectomy. The only predictor for developing chronically active UC regardless of disease extension was the lack of adherence to therapy within the first 3 years after diagnosis, underlining the importance of tight control of UC patients and the need to timely identify potential risk factors for non-adherence.

Background/Objectives: Patients with inflammatory bowel disease (IBD) are at increased risk of severe infections, particularly when undergoing immunosuppressive therapy. Vaccination is a key preventive strategy, but coverage in this group is often suboptimal. This study evaluated vaccination coverage among IBD patients at diagnosis/referral and after admission to a structured hospital-based vaccination pathway. Methods: We conducted an observational study (February 2022–February 2025) at the Vaccination Center (VC) of the University Hospital “G. Martino” in Messina, Italy. Adult IBD patients referred by gastroenterologists were assessed for vaccination status using hospital and regional registries, and personalized schedules were developed based on Italian National Vaccine Prevention Plan guidelines. Descriptive statistics were applied to assess baseline and post-intervention vaccination coverage. Results: Of 154 participants (mean age 64 years; 51.9% male), 55.4% were on immunosuppressive therapy. Baseline coverage was heterogeneous: influenza, 6.5%; PCV13, 25.5%; PPV23, 26.6%; herpes zoster, 62.3%; and COVID-19 primary cycle, 79.6%. After enrollment, substantial improvements were observed: influenza, 89.2%; PCV13, 74.5%; PPV23, 67.0%; herpes zoster, 75.4%; and COVID-19 primary cycle, 96.8%. Coverage for catch-up vaccines also improved (e.g., HBV went from 1.9% to 44.2%). However, uptake of COVID-19 booster doses during the study period remained low (15.6%). No significant differences emerged by sex or treatment subgroup. Conclusions: A structured, collaborative care pathway between gastroenterologists and public health specialists significantly improved vaccination coverage among IBD patients. Despite gains, gaps persist in COVID-19 booster uptake and catch-up vaccinations. Integration of vaccination services into routine IBD management is essential to enhance protection in this high-risk population.

Background/Objectives: Tumor necrosis factor alpha (TNF-α) is the key inflammatory cytokine involved in the pathogenesis of inflammatory bowel diseases (IBDs). Anti-TNF-α therapy has been successfully used for IBD treatment, although the therapeutic response differs among patients due to the genetic background. The aim of this study was to investigate whether the presence of single nucleotide polymorphisms (SNPs) on TNFA, TNFRSF1A, and TNFRSF1B genes could affect anti-TNF-α treatment effectiveness in IBD patients. Methods: In this prospective cohort study, 83 European IBD patients treated with infliximab or adalimumab (with or without steroid bridge therapy) as first-line therapy were enrolled. Genomic DNA was extracted from peripheral blood, and TNF-α (rs1800629, rs361525, rs1799724), TNFRSF1A (rs767455), and TNFRSF1B (rs1061622, rs1061624, rs3397, rs976881) SNPs were assessed. Steroid-free remission (SFR) (clinical remission together with steroid interruption) and anti-TNF-α therapy persistence after 12 months of follow-up were evaluated. Patients who stopped anti-TNF-α therapy before the end of follow-up, due to side effects or treatment failure, were defined as discontinuers. Results: A higher frequency of the G/G genotype in rs1800629 and the A/A genotype in rs1061624 was observed in the SFR group compared to non-SFR (97.7% vs. 82.8%; p = 0.025 and 32.6% vs. 10.3%; p = 0.029, respectively). Moreover, carriers of the A/A genotype in rs361525 and the C/C genotype in rs767455 had a lower probability of achieving SFR than wild-type patients (OR = 0.14; 95% CI= 0.03–0.69; p = 0.016 and OR = 0.10; 95% CI = 0.02–0.60; p = 0.012, respectively). Furthermore, an increased frequency of rs1800629 A allele was observed in patients who discontinued treatment compared to completers (27.3% vs. 6.9%; p = 0.033), as well as a high risk of interrupting therapy (HR = 6.47; 95% CI = 1.15–36.38). Conclusions: These results suggest that the evaluation of SNPs in TNF-α, TNFR1A, and TNFR1B genes could improve the management of IBD, leading to more effective, individualized treatment plans and a reduction in healthcare costs associated with ineffective therapies and disease complications.

Background: Patients with ulcerative colitis (UC) and Crohn’s disease (CD) have an increased cardiovascular risk (CVR). The aim of the present study was to stratify the CVR of patients with UC and CD according to the most recent guidelines via carotid ultrasound (US) to detect subclinical atherosclerotic disease. Methods: Demographic and disease-related data of consecutive patients with IBD were prospectively collected along with information on blood pressure, body mass index, lipid profile, and concomitant medications. CVR was stratified at inclusion according to the most recent version of Systematic Coronary Risk Evaluation 2 (SCORE2) and re-stratified after carotid US when subclinical atherosclerotic disease was detected. Results: A total of 166 patients aged ≥ 40 years with IBD were included. Before carotid US evaluation, 43.4% of patients with IBD were at moderate risk, 40.3% at high risk, and 16.3% at very high risk. With carotid US, subclinical atherosclerosis was diagnosed in 48% of patients, leading to CVR re-stratification from moderate to high in 18% of patients and from high to very high in 4% of patients. The only predictive factor for re-stratification was failure with more than two biologics (p = 0.047; OR 2.187, 95% CI: 1.004–4.741). Conclusions: CVR is considerably prevalent in patients with IBD. Carotid US may help to re-classify CVR and should be considered as a risk modifier in patients at intermediate risk. Screening for CVD risk factors should be recommended in IBD.