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The chronic inflammation of Crohn's disease is caused, at least in part, by repression of TGF-β1 signaling, which is caused by high levels of SMAD7. This trial shows that mongersen, an antisense inhibitor of SMAD7 mRNA, induces disease remission in some persons. Crohn’s disease is a chronic inflammatory illness that primarily affects the terminal ileum and right colon. Crohn’s disease–related inflammation is segmental and transmural, leading to various degrees of tissue damage. 1 At disease onset, most patients have inflammatory lesions, which become predominantly strictures or penetrating lesions over time. 2 , 3 Mucosal healing can be promoted with the use of immunosuppressive drugs and anti–tumor necrosis factor α (TNF- α ) antibodies; however, more than one third of patients do not have a response to these therapies. The efficacy of these drugs may also diminish over time, and they can increase a patient’s risk . . .

Thiopurines are employed in inflammatory bowel diseases (IBDs; Crohn’s disease, CD; ulcerative colitis, UC) to induce remission, prevent relapse, and reduce the steroid dosage, although they can sometimes be ineffective and present side effects. Genetic variations in the TPMT and NUDT15 genes are well recognized to influence the therapeutic response, despite notable regional differences in their frequencies across various ethnic populations. Herein, the risk haplotypes TPMT*3A, *3B, *3C, and the variant NUDT15*3 were examined in a retrospective cohort of 383 Italian IBD patients who received azathioprine or 6-mercaptopurine. TPMT and NUDT15 genotyping was performed by Sanger sequencing and TaqMan allelic discrimination, respectively. Allelic and genotype frequencies and genotype–phenotype correlations in non-responder and intolerant patients were assessed in comparison to responders. In total, 17% of patients did not respond to treatment, while 20% experienced adverse events, with leukopenia found in 13% of patients. TPMT haplotypes were found in 3.1% of patients, and 1.6% had the NUDT15*3 variant. CD patients with leukopenia had a higher frequency of the TPMT risk haplotype (40% vs. 4%, p = 0.024). Although additional validation through larger prospective studies or meta-analyses is needed, our findings support the importance of TPMT gene-variant assessment for forecasting azathioprine-related leukopenia in Italian IBD patients.

Background and Objectives: Telemedicine has become an essential component of chronic Inflammatory Bowel Disease (IBD) care, yet the factors that shape patient satisfaction with remote consultations remain only partially understood. This study aimed to assess satisfaction with institutional telemedicine services among Italian patients with ulcerative colitis (UC) and Crohn’s disease (CD), and to identify sociodemographic, clinical and organisational predictors to inform more person-centred telehealth models. Materials and Methods: We conducted a prospective, multi-centre, cross-sectional study in three IBD units in northern, central and southern Italy between June and October 2024. Consecutive adult patients who had completed a scheduled, non-emergency telemedicine visit were invited within 24–48 h to complete an online questionnaire including the Italian Telemedicine Satisfaction Questionnaire (I-TSQ), sociodemographic items, IBD-related variables, and telemedicine process indicators (accessibility, technology usability, technical support, time saved). Data were analysed descriptively and with multivariable linear regression to determine independent predictors of satisfaction, adjusting for recruiting centre. Results: A total of 705 patients participated (54.9% UC; 55.3% disease duration > 10 years). Overall, telemedicine satisfaction was high (mean I-TSQ total 57.5 ± 4.9; range 35–70), and all respondents reported reduced indirect costs compared with in-person visits. Greater ease of technology use, more frequent contact with the care team, male sex, older age, and employment were independently associated with higher satisfaction scores. Conversely, first-ever teleconsultations, CD, subcutaneous therapies, more difficult platform access, and the need for technical support were linked to lower satisfaction. Model fit was modest (R2 up to 0.20), suggesting the presence of additional unmeasured relational and contextual factors. Conclusions: Telemedicine for IBD is widely accepted in Italy, but satisfaction is strongly conditioned by digital usability, previous experience, and clinical complexity. Tailored telehealth pathways that incorporate user-friendly platforms, proactive technical support, and attention to vulnerable subgroups are needed to translate high satisfaction into sustained, equitable remote care.

Background: The efficacy of tofacitinib (TOFA) in various rheumatic diseases has generated interest in its potential benefits for treating spondyloarthritis (SpA) associated with ulcerative colitis (UC). Objectives: RETUCAS (Real-world Effectiveness of Tofacitinib on Ulcerative Colitis-Associated Spondyloarthropathy) is the first study designed to evaluate the effectiveness of TOFA in UC-associated SpA. Design: This was a prospective, multicentre, single-arm, observational study promoted by the Italian Group for the Study of Inflammatory Bowel Disease. Effectiveness was assessed using standardized rheumatologic scores. Methods: Patients with UC and a confirmed diagnosis of active axial or peripheral SpA at baseline were enrolled. The primary endpoint was steroid-free joint response (SFJR) at weeks 8 and 52, defined as a decrease of ⩾1.1 units in Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (CRP) for axial SpA, or a decrease of >0.6 units in Disease Activity Score 28-CRP for peripheral SpA, without the use of corticosteroids. Results: A total of 44 patients were enrolled: axial SpA: 9.1%; peripheral SpA: 70.4%; mixed axial and peripheral SpA: 20.5% All but two patients had previous exposure to biologic therapies, with more than half having failed two or more biologics. At week 8, SFJR was achieved in 52.3% of patients, with a significant difference between those with peripheral SpA and those with axial or mixed forms (67.7% vs 15.4%; p = 0.001). At week 52, SFJR was maintained in 59.1% of patients overall, again with better outcomes in peripheral SpA compared to axial/mixed SpA (71.0% vs 30.8%; p = 0.01). Conclusion: This is the first prospective study specifically designed to assess Inflammatory Bowel Diseases-associated SpA. In patients with UC and refractory SpA—many of whom had previously failed multiple biologic therapies—TOFA demonstrated effectiveness, particularly in those with peripheral SpA. Plain language summary Tofacitinib helps control joint symptoms in people with ulcerative colitis: Results from a real-world Italian study People with ulcerative colitis (UC) often experience joint inflammation, a condition known as spondyloarthritis (SpA). This study looked at whether a medication called tofacitinib, already used for UC and some joint diseases, could also help manage joint problems linked to UC. Researchers across multiple centers in Italy followed 44 patients with UC and active joint symptoms (either in the spine, limbs, or both) who started taking tofacitinib. They checked whether the patients’ joint symptoms improved without needing steroids after 8 weeks and again after 1 year. After 8 weeks, about half of the patients showed improvement without using steroids. The results were more positive in patients with joint problems in the limbs (called peripheral SpA) compared to those with spinal involvement (axial SpA). After 1 year, around 6 in 10 patients had improved, again with better results seen in peripheral SpA. This is the first study focused specifically on UC-related joint inflammation using rheumatology-specific tools. It suggests that tofacitinib can be effective for joint symptoms, especially in the limbs, in patients with UC who have not responded to other treatments.

Recent evidence suggests that the IL-33/IL1RL1 axis plays a critical role in several autoimmune and inflammatory disorders; however, its mechanistic role in inflammatory bowel disease (IBD) has not been clearly defined. We investigated the contribution of IL-33 and IL1RL1 polymorphisms to IBD risk, and possible correlations with phenotype in an Italian cohort of adult and pediatric patients. We evaluated the association of six SNPs in IL-33 and IL1RL1 genes, in 805 Crohn's disease (CD), 816 ulcerative colitis (UC), and 752 controls, using Taqman. IL-33 and IL1RL1 mRNA expression was also analyzed. Significant allele and genotype associations with IL-33 rs3939286 were found in CD (P = 0.004; P = 0.035) and UC patients (P = 0.002; P = 0.038). After stratifying the cohort for age at diagnosis, the differences remained significant only in the IBD adult-onset. Significant associations were also obtained in CD patients with two IL1RL1 polymorphisms (rs13015714 and rs2058660, P<0.015). By combining homo- and heterozygous carriers of the rs13015714 risk allele, differences were still significant for both CD adult- and pediatric-onset. Upon genotype-phenotype evaluation, an increased frequency of extensive colitis in adult UC (P = 0.019) and in steroid-responsive pediatric patients (P = 0.024) carrying the IL-33 rs3939286 risk genotype, was observed. mRNA expression of IL-33 and IL1RL1 in inflamed IBD biopsy samples was significantly increased. Common IL-33 and IL1RL1 polymorphisms contribute to the risk of IBD in an Italian cohort of adult and pediatric patients, with some influence on sub-phenotypes.

Richard Duerr and colleagues present a genome-wide association study of ulcerative colitis. They identify new risk loci on chromosomes 1p36 and 12q15. Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 × 10 −13 , combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 × 10 −12 , combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 × 10 −16 , combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 × 10 −8 , combined OR = 0.56; rs10889677, combined P = 1.3 × 10 −8 , combined OR = 1.29).

Inflammatory bowel diseases (IBD) are chronic, relapsing inflammatory disorders with ulcerative colitis (UC) and Crohns disease (CD) representing the two major phenotypes. While these conditions share common features, they exhibit distinct clinical presentations, disease behaviors, and pathogenetic mechanisms, highlighting the complexity of IBD. The global incidence and prevalence of IBD have risen dramatically in recent decades, probably linked to environmental changes such as dietary habits, urbanization, and reduced microbial exposure during early life, highlighting the interplay between environmental and genetic factors in disease pathogenesis. However, genetic factors alone cannot fully explain disease onset, emphasizing the critical role of environmental and microbial influences. Dysbiosis, characterized by reduced microbial diversity, loss of beneficial commensals, and an overabundance of pathogenic taxa, has emerged as a hallmark of IBD. Recent research has increasingly focused on the functional consequences of dysbiosis, its impact on microbial metabolites and pathways that contribute to chronic inflammation and disease progression. Understanding the functional implications of multi-omics changes, rather than simply cataloguing compositional changes, is now a priority in IBD research. Using artificial intelligence to combine data from noninvasive multi-omics technologies offers a significant opportunity to explore interactions among individual omics. It could represent a shift in IBD research by showing the complex mechanisms behind disease. This approach may revolutionize diagnostics and treatments, improving the quality of life for patients through precision medicine. This review aims to provide a comprehensive assessment of current progress. It highlights critical challenges and suggests possible future directions.

Growing evidence suggests that alterations in the gut microbiome impact the development of inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC). Although IBD often requires the use of immunosuppressant drugs and biologic therapies to facilitate clinical remission and mucosal healing, some patients do not benefit from these drugs, and the reasons for this remain poorly understood. Despite advancements, there is still a need to develop biomarkers to help predict prognosis and guide treatment decisions. The aim of this study was to investigate the gut microbiome of IBD patients using biologics to identify microbial signatures associated with responses, following standard accepted criteria. Microbiomes in 66 stool samples from 39 IBD patients, comprising 20 CD and 19 UC patients starting biologic therapies, and 29 samples from healthy controls (HCs) were prospectively analyzed via NGS and an ensemble of metagenomics analysis tools. At baseline, differences were observed in alpha and beta metrics among patients with CD, UC and HC, as well as between the CD and UC groups. The degree of dysbiosis was more pronounced in CD patients, and those with dysbiosis exhibited a limited response to biological drugs. Pairwise differential abundance analyses revealed an increasing trend in the abundance of an unannotated genus from the Clostridiales order, Gemmiger genus and an unannotated genus from the Rikenellaceae family, which were consistently identified in greater abundance in HC. The Clostridium genus was more abundant in CD patients. At baseline, a greater abundance of the Odoribacter and Ruminococcus genera was found in IBD patients who responded to biologics at 14 weeks, whereas a genus identified as SMB53 was more enriched at 52 weeks. The Collinsella genus showed a higher prevalence among non-responder IBD patients. Additionally, a greater abundance of an unclassified genus from the Barnesiellaceae family and one from Lachnospiraceae was observed in IBD patients responding to Vedolizumab at 14 weeks. Our analyses showed global microbial diversity, mainly in CD. This indicated the absence or depletion of key taxa responsible for producing short-chain fatty acids (SCFAs). We also identified an abundance of pathobiont microbes in IBD patients at baseline, particularly in non-responders to biologic therapies. Furthermore, specific bacteria-producing SCFAs were abundant in patients responding to biologics and in those responding to Vedolizumab.

The pathogenesis of ulcerative colitis (UC) is unknown, although genetic loci and altered gut microbiota have been implicated. Up to a third of patients with moderate to severe UC require proctocolectomy with ileal pouch ano-anastomosis (IPAA). We aimed to explore the mucosal microbiota of UC patients who underwent IPAA. Methods: For microbiome analysis, mucosal specimens were collected from 34 IPAA individuals. Endoscopic and histological examinations of IPAA were normal in 21 cases, while pouchitis was in 13 patients. 19 specimens from the healthy control (10 from colonic and 9 from ileum) were also analyzed. Data were analyzed using an ensemble of software packages: QIIME2, coda-lasso, clr-lasso, PICRUSt2, and ALDEx2. Results: IPAA specimens had significantly lower bacterial diversity as compared to normal. The microbial composition of the normal pouch was also decreased also when compared to pouchitis. Faecalibacterium prausnitzii, Gemmiger formicilis, Blautia obeum, Ruminococcus torques, Dorea formicigenerans, and an unknown species from Roseburia were the most uncommon in pouch/pouchitis, while an unknown species from Enterobacteriaceae was over-represented. Propionibacterium acnes and Enterobacteriaceae were the species most abundant in the pouchitis and in the normal pouch, respectively. Predicted metabolic pathways among the IPAA bacterial communities revealed an important role of immunometabolites such as SCFA, butyrate, and amino acids. Conclusions: Our findings showed specific bacterial signature hallmarks of dysbiosis and could represent bacterial biomarkers in IPAA patients useful to develop novel treatments in the future by modulating the gut microbiota through the administration of probiotic immunometabolites-producing bacterial strains and the addition of specific prebiotics and the faecal microbiota transplantation.

BackgroundGolimumab is a new anti-TNF-alpha monoclonal antibody for patients with ulcerative colitis.AimsTo assess the short- and long-term effectiveness and safety of golimumab in daily clinical practice and to identify predictors of response.MethodsConsecutive patients treated with golimumab in 22 Italian centers were enrolled. Clinical, laboratory, and endoscopic data were prospectively collected before and during treatment. A subgroup of patients completed a questionnaire to assess personal satisfaction with a golimumab autoinjector system.ResultsA total of 196 patients were included. After 3 months, 130 patients were responders (66.3%) and showed significant reductions in mean partial, total, and endoscopic Mayo scores and in mean ESR, C-reactive protein, and fecal calprotectin levels (p < 0.001). Multivariate analysis revealed that a higher total Mayo score (p < 0.001, OR 1.5, 95% CI 1.2–1.8) and naïve status to anti-TNF-alpha (p = 0.015, OR 3.0, 95% CI 1.2–7.5) were predictive of a favorable response. Seventy-seven (39.3%) of the 130 responders maintained a response at month 12 of therapy. There were 17 adverse events, 28 patients needed hospitalization, and 15 patients underwent surgery. Self-administration of the drug was appreciated by most patients.ConclusionsThe efficacy and safety of golimumab in daily clinical practice were confirmed for the short- and long-term treatment of patients with active ulcerative colitis. Patients naïve to the anti-TNF-alpha monoclonal antibody and those with a higher total Mayo score were more likely to respond to golimumab.