AIM:to assess the effectiveness and safety of Risankizumab (RZB) in a large, nationwide real-world cohort of Crohn's disease (CD) patients. METHODS:We conducted a multicentre, retrospective observational cohort of adults initiating RZB with assessments at weeks 12, 26, and 52. Co-primary endpoints were (i) week-12 steroid-free clinical remission (SFCR) (HBI <5 in the absence of systemic corticosteroids or budesonide) and (ii) week-52 endoscopic remission (SES-CD 0-2 or Rutgeerts i0-i1 post-operatively). The main effectiveness analysis was as-observed; a preplanned sensitivity analysis included patients expected to reach week-52 before database lock and applied non-responder imputation. RESULTS:We included 520 patients, 45.0% failed ≥3 and 54.8% were ustekinumab-exposed. At week 12, clinical response was 76.5% and 60.8% achieved SFCR. By week 52, SFCR was 65.6%; endoscopic remission occurred in 37.5%, while radiologic remission and transmural healing were 24.6% and 9.8%, respectively. Ustekinumab-naïve patients showed significantly superior early clinical outcomes (week-12 SFCR: 69.8% vs 53.3%) and a higher rate of endoscopic remission at week 52 (56.5% vs 28.6%) compared with ustekinumab-exposed patients. Notably, week-52 effectiveness was comparable between patients with 2 and those with ≥3 prior failures. Extra-intestinal manifestations decreased over time, while perianal disease improved modestly. In the sensitivity cohort (N = 213), SFCR was 47% at week-52. Risankizumab was well-tolerated with no new safety signals identified. CONCLUSIONS:In a large, refractory, real-world CD population, RZB induced rapid and sustained favorable clinical, endoscopic, and radiologic outcomes. Importantly, one-year effectiveness was similar in patients with 2, and ≥3 prior failures, supporting RZB as a valuable option for a refractory population.

Long-term real-world data on vedolizumab outcomes remain limited: the LONG-LIVE study evaluates 5-year effectiveness and safety in a large Italian cohort. This is a long-term extension of the multicenter LIVE study involving patients with Crohn’s disease (CD) and ulcerative colitis (UC). The primary outcome was the cumulative probability of major adverse clinical outcomes (the composite of IBD-related surgeries, non-surgical hospitalizations, and serious adverse events). Secondary outcomes included cumulative incidences of IBD-related surgery and non-surgical hospitalization, vedolizumab persistence, rates of death, cancer and adverse events of special interest (AESIs), and longitudinal response group transitions; outcomes in elderly patients (≥ 65 years) were compared to non-elderly using inverse probability weighting (IPW). Overall, 782 patients were included (50.4 Vedolizumab is a gut-selective biologic therapy approved for Crohn's disease (CD) and ulcerative colitis (UC). While its short-term effectiveness is well established, data on what happens to patients beyond 2 years of treatment remain limited. In this study, we followed 782 patients for up to 7 years across 47 Italian centers to track hard clinical outcomes: surgery, hospitalization, serious adverse events, and death. About one in three patients experienced a major adverse clinical outcome over 5 years—a composite endpoint that includes IBD-related surgeries, non-surgical hospitalizations, and serious adverse events—with no meaningful difference between CD and UC. Surgery occurred in approximately one in five patients, and non-surgical hospitalizations were more frequent in CD. Serious adverse events, including deaths, cancers, and infections, remained uncommon throughout follow-up. Patients who responded early to treatment were more likely to achieve deep remission within 2 years, which was in turn associated with deep remission at last follow-up. Elderly patients faced higher risks of hospitalization and major adverse clinical outcomes, but not of cancer or serious adverse events, suggesting that vedolizumab can be used across different age groups without a disproportionate increase in safety risk.

BACKGROUND & AIMS:Controlled real-world evidence on nonmedical switching from reference ustekinumab to biosimilars in Crohn's disease (CD) is limited. We compared 6-month outcomes after switching versus continued reference treatment. METHODS:In this prospective observational cohort at 18 Italian centers, adults with CD in clinical remission (Harvey-Bradshaw Index <5), steroid-free for ≥8 months of reference ustekinumab, underwent a procurement-driven switch to 1 of 3 approved biosimilars or continued reference treatment. The expanded clinical-success endpoint required clinical remission without systemic corticosteroids, anti-interleukin-12/23 discontinuation, inflammatory bowel disease-related hospitalization, or intestinal surgery. The protocol-specified noninferiority margin was -15%. RESULTS:Among 462 patients, 337 switched and 125 continued reference ustekinumab; only 4 (0.9%) received every-4-week dosing. Expanded clinical success occurred in 306 of 332 switched patients (92.2%) and 114 of 123 controls (92.7%; risk difference, -0.5%, 95% CI -5.9 to 4.9), meeting the noninferiority criterion. Results were consistent for the protocol-defined three-component composite and after propensity-score weighting. Biosimilar persistence was 93.7%; switch-back occurred in 1.2%. Two adverse events were reported after switching. CONCLUSIONS:In clinically stable CD, observed 6-month effectiveness and safety after procurement-driven ustekinumab biosimilar switching were similar to continued reference treatment. Longer-term studies, particularly in patients receiving every-4-week dosing, are needed.

Inflammatory bowel diseases (IBD) are associated with a substantial hospitalization burden; disease-related malnutrition (DRM) may worsen outcomes and increase costs. This study aimed to estimate the cost of IBD-related hospitalizations in Italy and the additional economic burden associated with DRM using real-world data.

Disability is increasingly recognised as a relevant long-term endpoint in inflammatory bowel disease (IBD), yet its prognostic value in clinical practice remains underexplored. Accordingly, we aimed to characterize the longitudinal trajectories of disability over time in patients with IBD. This prospective multicenter study included IBD patients previously enrolled in the IBD-Disk validation cohort and followed for 24 months. Disability was assessed using the IBD-Disk. Moderate-to-severe disability was defined as a global score >40 (1,2). Demographic and clinical characteristics, including therapy, were collected at baseline. Patients’ disability was reassessed at 24 months. Clinical relapse, IBD-related hospitalisations, and therapeutic sequencing were also recorded Of the 402 patients initially enrolled, 304 (75.6%) completed the 24-month follow-up. Of these, 170 (55.9%) had ulcerative colitis (UC) and 134 (44.1%) Crohn’s disease (CD). At baseline, 131 patients (43.1%) with moderate-to-severe disability showed higher rates of clinically active disease compared with those with mild disability (60.3% vs 39.9%; p = 0.001). After 24 months, disability trajectories varied across patients. Among those with mild disability at baseline, 40 of 173 (23.1%) progressed to moderate-to-severe disability, while 59 of 131 (45.0%) with moderate-to-severe disability improved to mild disability [Fig. 1]. Nevertheless, the overall pattern of trajectories did not show significant directional asymmetry (McNemar test χ²=3.27, p = 0.070). Baseline moderate-to-severe disability was strongly associated with clinical relapse at 24 months (HR 2.37; 95% CI 1.39–4.06; p = 0.002), and this association remained significant after adjusting for sex, type of IBD, age, biological therapy, active disease, and extraintestinal manifestations. Moderate-to-severe disability also predicted IBD-related hospitalisations (HR 3.10; 95% CI 1.15–8.39; p = 0.026). In contrast, no independent association was observed between moderate-to-severe disability and treatment sequencing (HR 1.31; 95% CI 0.84–2.03; p = 0.23), although a trend toward significance was observed [Fig. 2]. Notably, treatment sequencing was strongly associated with active disease (HR 0.53; 95% CI 0.34–0.82; p = 0.004). Overall, 14 patients (4.6%) underwent surgery at 24 months, with no significant difference between patients with moderate-to-severe and mild disability (7.6% vs 2.3%; p = 0.055). Moderate-to-severe disability was independently associated with a higher risk of clinical relapse and IBD-related hospitalisation over 24 months, supporting its role as a measure of comprehensive and sustained disease control. References: 1. Tadbiri S, et al. The IBD-disk Is a Reliable Tool to Assess the Daily-life Burden of Patients with Inflammatory Bowel Disease. Journal of Crohn’s and Colitis. 2021 May 4;15(5):766–73. 2. Tannoury J, et al. Determinants of IBD-related disability: a cross-sectional survey from the GETAID. Aliment Pharmacol Ther. 2021 May;53(10):1098–107. Conflict of interest: Dr. Nardone, Olga Maria: Advisory board fees from Eli Lilly, Nestlè, Janssen Speaker fees from AbbVie, Janssen, Eli Lilly, Ferring, Alfa Sigma, Recordati, Noòs, and Pfizer Calabrese, Giulio: Travel grant by Johnson and Johnson Speaker fee by Celltrion Caprioli, Flavio: Flavio Caprioli served as consultant to: Abbvie, Amgen, MSD, Takeda, Janssen, Roche, Celgene, Bristol-Meyers Squibb, Galapagos, Gllead, Pfizer, Mundipharma, Biogen, Ferring, Eli-Lilly, Nestlè, Lionhealth, AlfaSigma, Dr Falk, Celltrion, Abivax. He received lecture fees from Abbvie, Ferring, Takeda, Allergy Therapeutics, Janssen, Pfizer, Biogen, Sandoz, Tillotts Pharma, Vifor Pharma, AlfaSigma, Celltrion, Eli-Lilly. and unrestricted research grants from Giuliani, Sofar, MSD, Takeda, Abbvie, Celltrion, Pfizer, Actial. Fantini, Massimo Claudio: MCF has acted as a consultant for: AbbVie, AlfaSigma, Celgene, Celltrion, Gilead, Pfizer, MSD, Bristol-Meyer, Takeda, Johnson & Johnson, Roche, Galapagos, Biogen, Sandoz, Eli-Lilly, Lionhealth, Teva, Giuliani, Dr Falk Pharma, Sanofi he has received financial support for research from Johnson & Johnson and Pfizer. Onali, Sara: Consultant/lecture fees to: Abbvie, Alfasigma, MSD, Takeda, J & J, Galapagos, Pfizer, Eli Lilly Orlando, Ambrogio: Advisory board and/or lecture fees for: AbbVie, Galapagos, Celltrion, MAD, Sofar, Pfizer, Takeda, Cadigroup, Sandoz, Janssen, Eli-Lilly, Alfasigma Savarino, Edoardo Vincenzo: Personal Fees: Takeda, Abbvie, MSD, Janssen, Sofar Variola, Angela: Consultant for Abbvie, Alfasigma, Celltrion, Eli-Lilly, Johnson and Johnson, Takeda, Pfizer Speaker fee for Abbvie, Alfasigma, Celltrion, Eli-Lilly, Johnson and Johnson, Ferring, Takeda, Pfizer, Zamboni Vastarella, Josephine: No conflict of interest to declare Guarino, Alessia Dalila: No conflict of interest Rispo, Antonio: None Testa, Anna: Consultant /Advisory board for Abbvie, J & J, Takeda, Ferring Castiglione, Fabiana: Honoraria from: Takeda, AbbVie, Celltrion, Johnsson Johnsson, Cadigroup, Sandoz, Pfizer, Lilly, Lionhealth, Nestlè

PURPOSE:This study aimed to present real-world data regarding the treatment of inflammatory bowel disease (IBD) with the subcutaneous (SC) formulation of the tumor necrosis factor inhibitor, infliximab. METHODS:Adult IBD patients who switched from intravenous (IV) infliximab to SC infliximab were recruited for this study. Data on the efficacy of maintaining long-term remission, persistence in therapy and the safety profile were obtained from medical records and physician assessments conducted during routine clinical practice. Data on adherence to treatment schedules and patient satisfaction were collected through an ad hoc questionnaire. The duration of the follow-up was 12 months. RESULTS:The treatment with SC infliximab was generally well-tolerated, with a persistence rate of 86.7 ​% at 12 months and adherence to the treatment schedule of 86.4 ​%. Patients reported a favorable experience with self-injections. Mild, self-limiting adverse events were observed, and inflammatory biomarkers decreased over time, suggesting maintenance of remission in most patients. CONCLUSIONS:The findings suggest that SC infliximab may be a viable option for IBD patients in remission who are eligible for switching, offering a self-administered alternative to IV therapy.

BACKGROUND:IBD-PODCAST was a global real-world study to assess suboptimal disease control (SDC) in patients with Crohn's disease (CD) and ulcerative colitis (UC) using STRIDE-II criteria. AIM:To evaluate quality of life (QoL), disease characteristics and control in patients with SDC, comparing perspectives of patients and healthcare providers (HCPs) in the Italian subpopulation. METHODS:IBD-PODCAST-Italy enrolled adult outpatients from 17 centers. The study used a combination of retrospective chart reviews and cross-sectional assessments to gather data on treatment, patient-reported outcomes (QoL, fatigue, work productivity) and clinical activity. Patient and HCP perceptions of disease control based on STRIDE-II criteria, which included clinical, laboratory and endoscopic findings were also assessed. RESULTS:SDC was identified in 53.4 % (95 % CI: 44-62.8 %) of CD and 49.0 % (95 % CI: 39.1-59.0 %) of UC patients. Those with SDC had lower short IBD questionnaire scores (45.9 ± 12.0) compared to optimal disease control (ODC) patients (57.4 ± 9.9). Extraintestinal manifestations and bowel urgency were more frequent in SDC patients. Physician-perceived SDC (14.5 %) was higher than patient-perceived SDC (8.8 %) and agreement between patient and HCP assessments was low. CONCLUSIONS:Patients with SDC experienced impaired QoL. The discrepancy between patient and physician perceptions of disease control, alongside objective measures, highlights the need for further research to optimize care and improve outcomes.

INTRODUCTION:Inflammatory bowel disease (IBD) poses significant clinical challenges due to its chronic, disabling nature. Despite established guidelines, care standards remain inconsistent globally. In 2020, the European Crohn's Colitis Organisation (ECCO) developed quality-of-care standards. The Italian Group for the Study of IBD (IG-IBD) aimed to adapt those recommendations to Italy. METHODS:A 42-member interdisciplinary panel used a Delphi consensus to evaluate and modify ECCO statements and levels of importance, incorporating patient representatives and regional experts. Those statements were revised, some missing statements were added, and a two-round voting session was held among participants. Agreement ≥80 % was needed to approve a statement. RESULTS:From 101 ECCO statements, 112 tailored criteria were developed. In comparison to the ECCO statements, 80 were confirmed with the same level of importance, 9 were confirmed with different levels of importance, 9 points were merged in a broader statement, 3 points were dropped out during the two voting rounds, and 12 were added as new points. CONCLUSION:The adapted standards provide a framework for standardizing IBD care in Italy. This model might help other countries in aligning with ECCO standards.

Background:The increasing availability of biological drugs (originators and biosimilars) in the last decade for inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), has led to complex switching patterns in real-world settings. Objectives:To describe the switching/swapping patterns of biological drugs in IBD patients in Italy over the last decade. Design:A retrospective cohort study was conducted using administrative data from 14 Italian regions (2010-2023) in the VALORE distributed database network. Methods:Patients with at least 1 year of look-back and follow-up, who initiated biological therapy with ⩾2 dispensations for IBD, were included. Switches, swaps (between biologic classes), multiple switches (⩾2), switch-backs, and re-transitioning (biosimilar to originator) were described. Predictors of multiple switches at 3 years were identified through COX regression analysis. Results:Among 28,073 first-ever users (55.8% Crohn's disease and 44.2% ulcerative colitis), most started with adalimumab (45.3%) or infliximab (39.6%). The F/M ratio was 0.79, with a median age of 41.0 years (IQR: 27.0-54.0). At 1, 3, and 5 years, switch/swap rates were 12.0%, 35.6%, and 52.6%, respectively, while multiple switches occurred in 18.7% at 5 years. Re-transitioning from biosimilar to originator occurred in 10% of patients who initially switched from originator to biosimilar of the same molecule. Tumor necrosis factor alpha (TNF-α) inhibitors switched more frequently and more rapidly than ustekinumab or vedolizumab. Depression and corticosteroid use were identified as predictors of multiple switches at 3 years of follow-up. Conclusion:About half of first-ever users of biological drugs who were treated because of IBDs switched or swapped within 5 years from treatment start. TNF-α drugs were more likely to switch or swap. They also swapped or switched more rapidly than vedolizumab and ustekinumab. Notably, 1 out of 5 had changed biologic therapy more than once at 5 years and, among those who switched to a biosimilar, 1 out of 10 re-transitioned to the originator.

BACKGROUND AND AIMS:Real-world studies on vedolizumab in inflammatory bowel disease (IBD) are often limited by small sample size and short follow-up. In this study, we investigated the 2-year effectiveness and safety of vedolizumab in patients with IBD, and applied eXplainable Artificial Intelligence (XAI) to identify predictors of both. METHODS:The Long-term Italian Vedolizumab Effectiveness (LIVE) study is multicentric, ambispective, observational study enrolling 1111 IBD patients (563 Crohn's disease, CD, 542 ulcerative colitis, UC). Steroid-free clinical remission (SFCR) at 24 months was the primary endpoint. A XAI model (eXtreme Gradient Boosting, XGB) was applied to identify the main clinical predictors of SFCR and development of adverse events (AEs). RESULTS:Rates of SFCR at 24 months were 31.6 % and 39.7 % in CD and UC patients, and 0.14 AEs per patient-year was recorded. On XGB analysis, previous exposure to anti-TNFα and older age were the most important drivers for the prediction of SFCR; lower baseline CRP levels and fewer comorbidities were the most important features associated with no development of AEs. CONCLUSIONS:Vedolizumab is effective and safe in IBD patients. XAI yielded promising results in identifying the most important predictors of SFCR and development of AEs.

ABSTRACTBackgroundImmune‐mediated inflammatory diseases (IMIDs) are a group of chronic conditions characterized by dysregulated immune responses and persistent inflammation. Rheumatoid arthritis (RA), spondyloarthritis (SpA), and ulcerative colitis (UC) exemplify prominent IMIDs, each presenting unique challenges for their management, that impact patient's quality of life (QoL). Obesity, marked by persistent low‐grade inflammation, influences the progression, response to treatment, and clinical management of patients with RA, SpA, and UC. Besides, the emerging role of sarcopenic obesity, a special subtype of obesity with malnutrition, should be considered in the definition of the appropriated therapeutic interventions.MethodsThis narrative literature review summarizes recent evidence on the interplay between obesity‐induced inflammation and IMIDs.ResultsObesity contributes to elevated levels of proinflammatory cytokines, influencing the inflammatory pathways common to IMIDs. White adipose tissue, acting as an endocrine organ, produces cytokines like TNF‐α and IL‐6, fueling chronic inflammation. The dysregulation of adipokines, such as leptin and adiponectin, further complicates this interplay, impacting immune responses and metabolic processes.ConclusionsUnderstanding the cross‐talk between inflammatory pathways in obesity and IMIDs can provide insight into potential targets for intervention. This includes lifestyle modifications aimed to regulate weight gain, paving the way for comprehensive strategies to manage IMIDs in the context of obesity.