Advanced Therapy Research Articles

Managing persistent neonatal hyperinsulinemic hypoglycemia: Insights from nesidioblastosis research

Background: Persistent neonatal hyperinsulinemic hypoglycemia (PNHH), frequently associated with nesidioblastosis, poses significant diagnostic and therapeutic challenges due to dysregulated insulin secretion. Congenital hyperinsulinism (CHI), the primary cause of PNHH, exhibits diverse genetic and phenotypic presentations, necessitating tailored management strategies. This review integrates insights from 20 studies, examining genetic, therapeutic, and psychosocial dimensions of CHI. Objectives: To evaluate genotype-phenotype correlations and their implications for therapeutic outcomes in CHI, compare long-term medical and surgical outcomes, and identify risk factors affecting growth, metabolism, and neurodevelopment. Additionally, the study explores effective strategies to address the psychosocial and dietary challenges associated with CHI. Methods: A systematic review of 20 studies, encompassing over 2,000 patients, was conducted. Diagnostic criteria included genetic analyses of mutations in KATP channel genes (ABCC8, KCNJ11), GLUD1, and HNF4A, along with imaging and histopathological assessments. Treatment efficacy, long-term outcomes, and the impact of caregiver burden were analyzed. Data were synthesized into thematic categories, supported by statistical and qualitative assessments. Results: Dominant KATP mutations exhibited high responsiveness to diazoxide (70%), whereas recessive mutations necessitated surgical interventions, particularly near-total pancreatectomy. Focal CHI resolved hypoglycemia effectively with lesionectomy, whereas diffuse CHI presented ongoing risks, including diabetes and neurodevelopmental impairments. Personalized dietary strategies, such as high-protein diets and gastrostomy feeding, were effective in stabilizing glucose levels. Psychological stress in caregivers emerged as a significant concern, emphasizing the need for supportive interventions. Emerging therapies like lanreotide showed promise in refractory CHI cases. Discussion: The findings align with prior research, confirming the role of genetic mutations in determining treatment responsiveness. Surgical interventions, though effective in resolving hypoglycemia, carry long-term metabolic risks. Recent advances in genetic diagnostics and personalized medical therapies highlight opportunities for optimizing outcomes. However, caregiver burden and psychosocial challenges remain underexplored areas that require structured support systems. Conclusion: Managing CHI necessitates a multidisciplinary approach, integrating genetic insights, advanced therapies, and psychosocial support. Continued research is essential to develop innovative solutions for refractory CHI cases and to improve long-term outcomes for patients and families.

Inadequate Therapy Response on Advanced Therapy in Ulcerative Colitis Adult Patients: A Retrospective Analysis of German Health Claims Data.

The treatment landscape for active ulcerative colitis is rapidly evolving and current real-world evidence on response to advanced therapy is limited. This study aimed to determine indicators of inadequate therapeutic response among patients with ulcerative colitis in Germany initiating advanced therapy. This retrospective analysis used German claims data (2015-2022) from adult patients (≥18years). The prevalence and incidence of ulcerative colitis (ICD-10-GM: K51.X) were estimated. Inadequate response to therapy was evaluated in patients initiating advanced therapy based on eight predefined indicators observed for 12months following dispensation of index treatment. Mean ulcerative colitis patient age in 2016-2022 ranged from 49.6 to 51.5years, 47.6%-48.3% were female. Administrative prevalence ranged from 0.45% in 2016 to 0.53% in 2022. The number of patients initiating advanced treatment ranged from 157 to 347 across the study years (3.2%-4.9% of overall treated study population). On average from 2016-2021, 78.8% had inadequate response in the 12months following index treatment. Common indicators included prolonged use of corticosteroids (46.2%) and augmentation with conventional therapies (43.9%). Adult ulcerative colitis patients showed a high prevalence of inadequate response to advanced therapies. Our findings reveal a need for improved UC advanced therapy options, providing insight into inadequate response patterns. This may help identify patients who could benefit from a change in therapy to improve long-term outcomes.

Comparative Improvement in Health-Related Quality of Life with Advanced Therapies for Moderate-to-Severe Crohn's Disease: A Network Meta-Analysis.

The comparative efficacy of advanced therapies to improve health-related quality of life (HR-QoL) in Crohn's disease (CD) is unknown. We aimed to compare the impact of approved advanced therapies for moderate-to-severe CD on HR-QoL. We searched MEDLINE, Embase, and Cochrane CENTRAL from inception to December 2023. We included randomized controlled trials (RCTs) that assessed approved advanced therapies for the treatment of adults with moderate-to-severe luminal CD. The primary outcome was change from baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ). Pairwise random-effects meta-analyses were conducted, and we reported results as mean differences (MD) for continuous outcomes and risk ratios for binary outcomes, with corresponding 95% confidence intervals (CI). A random-effects frequentist network meta-analysis was conducted, and the competing interventions were ranked using the P-score. Our search strategy 34 records that fulfilled our eligibility criteria. In pairwise meta-analysis, advanced therapies were associated with improvements in IBDQ score (MD 16.07, 95% CI 12.59 - 19.54) after induction. In network meta-analysis, upadacitinib 45mg ranked first for change in IBDQ after induction (MD 23.10, 95% CI 14.41 - 31.78, P-score 0.86). For maintenance studies, advanced therapies showed a significant improvement in IBDQ score in pairwise meta-analysis (MD 12.72, 95% CI 10.47 - 14.97). Infliximab 10mg/kg ranked first for change in IBDQ after maintenance (MD 24.91, 95% CI 12.99 - 36.83, P-score 0.90). Advanced therapies were associated with improvements in HR-QoL after induction and maintenance. Upadacitinib 45mg and infliximab 10mg/kg ranked highest after induction and maintenance, respectively.

Type 2 Diabetes Mellitus: New Pathogenetic Mechanisms, Treatment and the Most Important Complications

Type 2 diabetes mellitus (T2DM), a prevalent chronic disease affecting over 400 million people globally, is driven by genetic and environmental factors. The pathogenesis involves insulin resistance and β-cell dysfunction, mediated by mechanisms such as the dedifferentiation of β-cells, mitochondrial dysfunction, and oxidative stress. Treatment should be based on non-pharmacological therapy. Strategies such as increased physical activity, dietary modifications, cognitive-behavioral therapy are important in maintaining normal glycemia. Advanced therapies, including SGLT2 inhibitors and GLP-1 receptor agonists, complement these treatments and offer solid glycemic control, weight control, and reduced cardiovascular risk. Complications of T2DM, such as diabetic kidney disease, retinopathy, and neuropathy, underscore the need for early diagnosis and comprehensive management to improve patient outcomes and quality of life.

Promising LOX proteins for cartilage- targeting osteoarthritis therapy.

Osteoarthritis (OA) is the most affected joint disease worldwide, touching millions of people every year. It is caused by a progressive degeneration of articular cartilage, causing pain and limited mobility. Among the pathways involved in cartilage homeostasis, "LOX" proteins (referring to three distinct protein families, very often confused in the literature) play a prominent role. The lipoxygenase enzyme family is involved in the inflammatory process of OA by inducing the production of several pro-inflammatory leukotrienes. Lectin-like oxidized low-density lipoprotein family are receptors located at the surface of chondrocytes, which interact with their ligand, ox-LDL, activating several catabolic pathways involved in OA pathophysiology. Finally, lysyl oxidase and lysyl oxidase-like are enzymes expressed intracellularly in chondrocytes cytoplasm involved in elastin biosynthesis and collagen cross-linking in cartilage extracellular matrix. EMA and FDA have yet approved no drugs targeting the LOX proteins. In particular, lysyl oxidase-like 2 is considered today as a new promising target for OA modifying therapy. This review clarifies the main role of different LOX proteins involved in the progression of OA. Some potential LOX inhibitor strategies for drug development in advanced OA therapy, particularly for local intraarticular delivery, were listed and discussed for each target type. This review, therefore, proposes promising strategies for future drug development in OA treatment.

Validation of the FROM-16 in family members of patients receiving advanced therapy medicinal product (ATMP).

Outcome-based pricing models which consider domains of value not previously considered in healthcare, such as societal outcomes, are of increasing interest for healthcare systems. Societal outcomes can include family-reported outcome measures (FROMs), which measure the impact of disease upon the patient's family members. The FROM-16 is a generic and easy-to-use family quality of life tool, but it has never been used in the context of patients undergoing advanced therapy medicinal product (ATMP) treatment. The use of potentially curative ATMPs is limited due their high cost and the low number of eligible patients. Using the FROM-16 to collect the impact on family of disease and treatment in ATMP patients may demonstrate additional value created by an ATMP intervention and strengthen the case for its use. This feasibility study aimed to test the validity of the FROM-16 in family members of ATMP patients as a prelude for its use in ATMP value estimation. Patients and family members (n = 24) were recruited from ATMP treatment centres in England and Wales. Family members completed the FROM-16 and were invited to a short debriefing interview. The FROM-16 showed high validity demonstrated by strong internal consistency (Cronbach's alpha = 0.917) and intraclass correlation (0.803, 95%). Interviews identified that whilst the FROM-16 covered most areas of quality-of-life impact experienced by the participants, some explained that they also experienced other impacts upon their personal health and future outlook. This feasibility study provides evidence that the FROM-16 could be used as part of a structured systematic approach to measure family quality of life impact in ATMP patients.

Insights and trends review: Use of extended reality (xR) in hand surgery.

Digital transformation through extended reality (xR)-comprising virtual, augmented, mixed, and substitutional reality-has become an integral part of the future of clinical and surgical practice. xR technologies facilitate advanced surgical planning, training, therapies and education, reshaping both personal and institutional healthcare. This paper examines the potential changes that xR has introduced into the field of hand surgery, exploring how xR enhances patient-centric care, increases medical service efficiency and revolutionizes surgical training, planning and therapeutic interventions. Key areas such as surgical assistance, telemedicine, therapies and rehabilitation, medical training and education, and improving patient understanding are highlighted. By synthesizing the current literature, this narrative review articulates the theoretical and practical implications of xR, offering insights into its transformative potential and supporting continuous educational advancement in medical practice.

Harnessing Gut Microbiota for Biomimetic Innovations in Health and Biotechnology

The gut microbiota is a complex and dynamic ecosystem that plays a fundamental role in human health by regulating immunity, metabolism, and the gut–brain axis. Beyond its critical physiological functions, it has emerged as a rich source of inspiration for biomimetic innovations in healthcare and biotechnology. This review explores the transformative potential of microbiota-based biomimetics, focusing on key biological mechanisms such as resilience, self-regulation, and quorum sensing. These mechanisms have inspired the development of innovative applications, including personalized probiotics, synbiotics, artificial microbiomes, bioinspired biosensors, and bioremediation systems. Such technologies aim to emulate and optimize the intricate functions of microbial ecosystems, addressing challenges in healthcare and environmental sustainability. The integration of advanced technologies, such as artificial intelligence, bioengineering, and multi-omics approaches, has further accelerated the potential of microbiota biomimetics. These tools enable the development of precision therapies tailored to individual microbiota profiles, enhance the efficacy of diagnostic systems, and facilitate the design of environmentally sustainable solutions, such as waste-to-energy systems and bioremediation platforms. Emerging areas of innovation, including gut-on-chip models and synthetic biology, offer unprecedented opportunities for studying and applying microbiota principles in controlled environments. Despite these advancements, challenges remain. The replication of microbial complexity in artificial environments, ethical concerns regarding genetically engineered microorganisms, and equitable access to advanced therapies are critical hurdles that must be addressed. This review underscores the importance of interdisciplinary collaboration and public awareness in overcoming these barriers and ensuring the responsible development of microbiota-based solutions. By leveraging the principles of microbial ecosystems, microbiota biomimetics represents a promising frontier in healthcare and sustainability. This approach has the potential to revolutionize therapeutic strategies, redefine diagnostic tools, and address global challenges, paving the way for a more personalized, efficient, and sustainable future in medicine and biotechnology.

Cerebellar metastasis from colorectal cancer: a case report

IntroductionColorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with adenocarcinoma as the most common subtype. While metastasis typically occurs in the liver, lungs, and peritoneal cavity, metastasis to the brain, particularly the cerebellum, is exceedingly rare.Case presentationThis report discusses the case of a 50-year-old woman diagnosed with mucinous adenocarcinoma of the descending colon. Over six years, the patient experienced multiple common metastatic sites, including the liver and lungs, before developing a rare cerebellar metastasis. Despite extensive treatment, including surgery and chemotherapy, the disease progressed, ultimately leading to the patient’s demise. This case represents the first documented cerebellar metastasis from CRC in Mexico.ConclusionThis case highlights the altered metastatic patterns in CRC due to advanced therapies that extend survival. Clinicians should remain vigilant for metastasis to uncommon sites, such as the cerebellum, especially in patients with prolonged survival. Further research is needed to understand the mechanisms underlying such metastatic behavior and optimize treatment strategies.

The Impact of Advanced Medical Therapies on Time to Resection and Colorectal Cancer Outcomes in Ulcerative Colitis Patients Undergoing Colectomy.

We aimed to evaluate the impact of advanced medical therapies (biologicals and small molecules) on time to colectomy and oncological outcomes in UC. This cohort study included UC patients who underwent colectomy between 2003 and 2022 at two referral centres in Belgium and the Netherlands. Exposure was use of advanced medical therapies. Primary outcomes were time to colectomy and colorectal cancer (CRC) rate, compared between four periods: P1 (2003-2007), P2 (2008-2012), P3 (2013-2017), P4 (2018-2022). Secondary outcomes were oncological outcomes, including incidental cancers found unexpectedly in resection specimens or during endoscopic follow-up for medication switch. Among 716 patients, the usage of advanced therapies increased from 36.8% in P1 to 89.7% in P4 (p<0.0001). Median time to colectomy remained comparable (P1: 7.1 years [IQR, 2.8-12.9] vs P4: 7.2 years [IQR, 2.7-14.6]; p=not significant). CRC was diagnosed in 72 (10.1%) patients, with no significant change over time (p=0.44). Proportion of CRC was lower in patients treated with advanced therapies (4.7% vs 23.6%, p<0.0001), related to a shorter follow-up (median 6.1 vs 10.3 years, p<0.0001). Advanced therapy patients had higher incidental cancer rates (37.5% vs 8.3%, p=0.002), which was associated with reduced CRC-related survival (HR for CRC-related death: 3.3, 95% CI 1.17-9.4; p=0.02). Despite increased usage of advanced medical therapies, time to resection and CRC rates have remained unchanged in UC patients undergoing colectomy over the past two decades. Advanced therapy patients had higher incidental cancers rates, associated with decreased CRC-survival. Awareness of timely colectomy is crucial for this group.

P1126 Patterns of conventional therapy use and drivers of initiation for advanced therapy in Inflammatory Bowel Disease: A European situational analysis

Abstract Background Data suggest limited use of advanced therapies (AT) in inflammatory bowel disease (IBD) despite the accumulating data for the benefits of early, broader AT use.1-3 We evaluated barriers to AT use in IBD using a multimodal approach. Methods Market research was conducted June-November 2023. Quantitative survey on prescribing trends amongst gastroenterologists (GEs) prescribing ATs was conducted to capture AT initiation drivers in Germany, Italy, UK and US; questions for this survey were identified in qualitative interviews. GEs cycling an average of 0-1 and ≥2 conventional therapies (CTs) before initiating AT were classified as low and high cyclers, respectively. The COM-B (Capability, Opportunity, Motivation and Behaviour) model was used for behavioural analysis.4 Results Qualitative analysis covered responses from 62 participants (28 patients [pts], 24 GEs, 7 nurses, 3 pt organisation representatives), and quantitative analysis – from 142 GEs (Germany, 30; Italy, 30; UK, 30; US, 52) currently prescribing ATs, with 559 pt report forms (ulcerative colitis [UC], 280; Crohn’s disease [CD], 279) collected. CT cycling was more prevalent in UC vs CD; AT treatment was less likely in pts with UC vs CD (Figure). Differences among GEs by geography were only partially explained by cost containment in highly regulated markets (eg, Italy, UK). High cycling variations were linked to behavioural and belief-driven factors as illustrated by the notable use (7-20%) of 5-aminosalicylates in CD despite the lack of clinical guideline support. In behavioural analysis, AT initiation barriers included a lack of awareness of AT value and prescribing approach of exhausting all CT options before initiating AT. Low vs high cyclers placed higher importance on patient preference (UC, +16%; CD, +19%) and peer recommendations (UC, +13%; CD, +20%). In UC, the belief of exhausting all CT options before initiating AT was more important for high vs low cyclers (+9%). Qualitative research showed that the lack of clear guidelines disproportionately impacted high cyclers as they had reduced academic interest and limited capacity as contributors. Physician-relevant AT initiation drivers were the perceived CT risks and the growing recognition of the AT clinical value and long-term impact on the quality of life. Pt-relevant drivers included improved AT awareness and the ability and confidence for pts to self-advocate. Conclusion Cost containment and guideline variations could partially explain the observed geographic variations in AT use. Within any given country, clinical beliefs play a determining role. In Europe, a tangible increase in AT vs CT share could be achieved by encouraging GEs to initiate AT in pts with poor prognostic factors as per guideline suggestions.

P1205 Long-term treatment patterns, dose escalation, and steroid use among patients with moderate-to-severe ulcerative colitis using advanced therapies: &amp;gt;3 years of continuous follow up using IQVIA PharMetrics Plus database

Abstract Background Induction and/or maintenance of remission is seen in less than half of ulcerative colitis (UC) patients with advanced therapies (AT).1,2 This results in frequent switching, dose-optimization, and steroid use to maintain disease control. Long term characterization of these treatment patterns and treatment persistence is needed. Methods This retrospective study used the IQVIA PharMetrics® Plus database (2019-2023) to analyze adults in the United States with moderate-to-severe UC who received at least one AT. Baseline characteristics were assessed 6 months prior to AT initiation (index date). Patients were required to have no evidence of other autoimmune diseases at baseline and ≥3 years of continuous follow-up after AT initiation. Switching was defined as filling a prescription for a different AT than was used in the previous line. We further assessed the number of patients who had no claims for an AT following their index treatment (discontinuation), stratified by whether they had ≥1 year of follow-up after discontinuation. Subsequent lines of therapy were similarly examined. Dose escalation was defined as an increase in AT dose or a shortening of prescription intervals, derived from drug label indications and clinical input. Results Baseline characteristics and treatment patterns are summarized in Figures 1 and 2. The study included 2,188 patients, with a mean age of 38.6 years, of whom 54% were male. The mean follow-up duration was 46.3 months (median: 45.7 months). Among these patients, 28%, 13%, and 4% had no AT fill for at least one year following their last AT fill in the first, second, and third lines of therapy, respectively. Most patients initially received adalimumab, vedolizumab, or infliximab as their first-line AT, and 42% switched therapies at least once. Vedolizumab was the most common second-line AT. In the third and fourth lines, there was greater variation in AT use, with ustekinumab being the most frequent. Around 25-33% of patients experienced a dose escalation at some point in their treatment line. About 40% of patients had a glucocorticoid (prednisone or budesonide) prescription at the time of switching therapies, with usage increasing in later lines. Among patients with discontinuation, 40% used steroids at time or after discontinuing AT. Among patients with at least one year of follow-up after their last AT fill, 23% used steroids after discontinuing AT. Conclusion Advanced therapies for moderate-to-severe UC are associated with high rates of discontinuations, switching and dose escalations. Almost half of all patients completely discontinue AT for ulcerative colitis when followed for 3+ years.

P1234 Inflammatory Bowel Disease Trends and Advanced Therapy Utilization: Insights from the UAE

Abstract Background The Middle East is experiencing a rapid increase in inflammatory bowel disease (IBD) likely due to urbanization, dietary changes and environmental factors. The region lacks sufficient data, making it challenging to comprehend the full extent of IBD's impact on healthcare systems. This research aims to investigate IBD trends, disease behaviour, evolution and persistence of advanced therapy (AT) within a predominantly Arab patient population in UAE. Methods This observational study at a tertiary IBD centre in the UAE utilized the local IBD registry (prospective data collection from 2022). Data included disease characteristics, and AT usage. Descriptive statistics, regression models and Kaplan-Meier analysis were employed. Results Of the 859 IBD patients treated from 2012 to 2024, comprehensive data were available for 321 patients under active follow-up of which 64.2% comprised of Crohn’s disease (CD) and 35.8% with ulcerative colitis (UC). A ten-fold rise over a 22-year period in new diagnoses of IBD, particularly CD was observed. Median age at diagnosis was 25 years (IQR 25-42), with CD patients younger (24 years) than UC patients (28 years). Within CD, 20% had stricturing, 17% penetrating and 36% with perianal disease. 85% of CD and 61% of UC patients were exposed to at least one AT; 25% of CD and 18% of UC patients &amp;gt;2 ATs, and 16% of CD and 11% of UC &amp;gt;3 ATs. Infliximab and adalimumab were the main first-line ATs, while ustekinumab and risankizumab used in later AT lines. Ustekinumab and risankizumab, showed higher AT persistence compared to anti-TNFs. In CD, stricturing disease (p&amp;lt;0.05), penetrating disease (p&amp;lt;0.01), longer disease duration (p&amp;lt;0.05), and younger age at diagnosis (p&amp;lt;0.05) were linked to higher exposure to AT lines. In UC, younger age at diagnosis (p=0.001) was associated with increased number of AT exposures. Use of AT significantly changed between 2017–2020 and 2021–2024 (p&amp;lt;0.001). Infliximab, adalimumab and vedolizumab were initially the most prevalent, with ustekinumab, risankizumab, and upadacitinib usage rising substantially by 2022. The time to initiate AT for CD and UC following diagnosis decreased significantly since 2017 by 6.82 and 6.91 months per year, respectively (p&amp;lt;0.001), with a combined median time of 2.46 months (IQR 4.8) for CD for 2023-2024. Conclusion This is the first comprehensive evaluation of IBD in the UAE, highlighting a significant rise in new diagnoses, particularly CD with aggressive phenotypes, reflecting broader regional trends. AT utilization has evolved, with ustekinumab and risankizumab demonstrating better persistence and increasing adoption. These insights into disease patterns will help inform future regional healthcare policies.

P0962 Relationship between Total Corticosteroid Dose Prior to Advanced Therapy Induction and Primary Non-Response

Abstract Background The PROFILE study1) highlighted the importance of top-down treatment with Advanced Therapy (AT) in Crohn’s disease. In ulcerative colitis (UC), the corticosteroid (CS) treatment cascade remains crucial for selecting AT candidates. CS treatment efficacy decreases with repeated use, affecting therapeutic outcomes of GMA and carotegrast. We hypothesized that total CS dose impacts subsequent AT efficacy and examined this relationship to optimize AT induction timing. Methods We retrospectively reviewed medical records of UC patients diagnosed after January 2010, analyzing the correlation between total CS dose prior to initial AT administration and AT response. Patients using steroids for other diseases or with incomplete CS dose information were excluded. Variables assessed included onset age, sex, disease extent, activity (PRO2), treatment details, and treatment failure rates. Nominal variables were analyzed using Fisher’s exact test and logistic regression analysis. Results Data from 92 UC patients (44 males) were analyzed. Median onset age was 41.5 years, with median AT induction age of 46.5 years. Disease extent: total colitis/left-sided/rectum = 57/33/2. Mean total CS dose before AT initiation was 1,743.2 mg, with a mean 479.1 days between CS initiation and AT start. AT breakdown: IFX/ADA/GLM/VDZ/UST/UPA/TOF/FIL = 37/19/13/13/6/2/1/1. Median PRO2 at AT initiation was 4. (TABLE 1) Primary non-response (PNR) occurred in 23 cases (24.0%), and loss of response (LOR) in 18 cases (18.8%). Multivariate analysis identified total CS dose ≥3,000 mg as a significant risk factor for PNR (OR 4.21, 95%CI 1.32-13.5, p=0.02). (TABLE 2) No risk factors were identified for LOR. Conclusion As previously reported, elderly-onset UC requires careful management due to potentially poor treatment response. The total CS dose appears to significantly impact primary non-response, suggesting that early transition to Advanced Therapy may be crucial for optimal patient outcomes. References 1)Nurulamin MN. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn’s disease (PROFILE). Lancet Gastroenterol Hepatol. 2024;9(5):415-427 doi:10.1016/S2468-1253(24)00034-7

P0738 Apulian Network for Inflammatory Bowel Disease (AN-IBD) safety profile: Pilot data

Abstract Background The Apulian Network for Inflammatory Bowel Disease (AN-IBD) is a prospective observational regional database recently approved by the Ethics Committee in Apulia (Italy), enrolling all IBD patients with an established diagnosis and focusing on the safety and effectiveness of all licensed therapies. We aimed to evaluate the safety profile of IBD therapies registered in patients enrolled in the participating centres and to record the occurring adverse events. Methods The AN-IBD involves 19 centres across Apulia, selected based on their capacity to prescribe advanced IBD therapies. In the six months following the ethical approval, we recorded unselected patients in the database and stratified them by disease type, age, sex and type of treatment. The occurrence of infusion reactions (local and systemic), infections, IBD-related hospitalization, need for colectomy, malignancies, thromboembolic events, and laboratory alterations were recorded. Their severity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results A total of 420 patients were enrolled, consisting of 251 males (59,76%) and 169 females (40,24%), with a median age of 44 years. Among them, 243 (57,86%) were diagnosed with ulcerative colitis, 156 (37,14%) with Crohn’s disease and 21 (5%) with unclassified colitis. Overall, 341 patients (81,19%) were treated with advanced therapy, including biologic therapy and small molecules. A total of 33 (7,85%) adverse events were recorded comprehensively, and most of them were graded as moderate according to the CTCAE. Twenty-three patients were treated with biologic therapy (70%), seven with small molecules (21%), one with immunomodulators (3%) and two with conventional therapy (6%). The most common adverse events were infusion reactions, with fourteen cases recorded (42%), followed by eight cases of infective complications (24%), predominantly due to cytomegalovirus reactivation. Other recorded adverse events included IBD-related surgery (15%), malignancies (9%) and altered liver enzymes (9%). Conclusion These preliminary findings evaluate the real-world prevalence and nature of adverse events among the population enrolled in our newly developed multicentre regional cohort. The establishment of this new database, given the absence of a national registry, will allow for closer monitoring of IBD patients undergoing conventional and advanced therapies and will increase awareness of the safety of these treatments.

P0957 Flow of Advanced Therapy Pathways and Variations over Time in Crohn’s Disease and Ulcerative Colitis: Data from the Persistence Australian National IBD Cohort (PANIC5)

Abstract Background Choice of advanced therapy (AT) in Crohn’s disease (CD) and ulcerative colitis (UC) have increased, however the optimal positioning and sequencing of agents are unknown. We present the first national data on sequencing for all AT treatments in Australia with Sankey diagrams. Methods We analysed the Persistence Australian National IBD Cohort (PANIC) 5 registry, including all UC and CD patients on AT via the Pharmaceutical Benefits Scheme up to December 2021. Sankey diagrams were created using Plotly, a Python-based tool. Each AT was coded as a node along the x-axis, and the y-axis represented patients’ treatment pathways, including sequential switches and stops from first to fifth-line treatments. Patients were divided into tertiles based on first AT commencement date (T1, T2, and T3) for both UC and CD data, and trends across these periods were compared. Statistical analyses were performed using SPSS. Results In a cohort of 9,671 UC patients (23,220 patient-years), 45% (n=539) discontinued first-line treatment in T1, which was 2.8 times more likely compared to 16% in T3 (p &amp;lt; 0.001). Additionally, 15% of patients in T1 transitioned to a second advanced therapy (AT), whereas 35% did so in T3 (p &amp;lt; 0.001). TOF was less frequently used in bio-naïve patients but more commonly prescribed in bio-exposed patients. Notably, in T3, TOF was the only therapy to show a significant increase in use from first- to fifth-line treatment, with the number of patients rising from 84 to 330, a 293% increase. In a cohort of 19,087 CD patients (79,677 patient-years), 48% (n=1465) discontinued first-line TNFi treatment in T1, making them 2.1 times more likely to stop treatment compared to T3 (p &amp;lt; 0.001). Due to limited treatment options in T1, only 20% of patients transitioned to second-line advanced therapy (AT), compared to 38% in T3. Furthermore, with the introduction of UST in T3, it was 2.1 times more likely to be prescribed to bio-exposed patients than ADA, the second most commonly used therapy in this group during T3. Conclusion This study underscores the increasing diversity of AT pathways for IBD patients, resulting in improved treatment retention over time. In both Crohn’s disease and ulcerative colitis, patients in T3 were less likely to discontinue treatment compared to those in T1, largely due to the expanded use of TOF and UST as salvage therapies. These findings provide important insights into the optimal sequencing of AT in IBD, demonstrating that a broader array of treatment options enhances patient adherence by offering more effective salvage strategies. References Ko Y, Paramsothy S, Yau Y, Leong RW. Superior treatment persistence with ustekinumab in Crohn’s disease and vedolizumab in ulcerative colitis compared with anti-TNF biological agents: real-world registry data from the Persistence Australian National IBD Cohort (PANIC) study. Aliment Pharmacol Ther. 2021 Aug;54(3):292-301. doi: 10.1111/apt.16436. Epub 2021 Jun 20. PMID: 34151447.

P1090 Increased advanced therapy prescribing correlates with decreased colectomy rates in ulcerative colitis: a twenty-year population-based cohort study in Lothian, Scotland

Abstract Background The evidence for the impact of increased advanced therapy prescribing on colectomy rates in ulcerative colitis (UC) are conflicting. Our aim was to describe prescribing trends of advanced therapies (biologics and small molecules) for patients with UC in Lothian, UK and colectomy rates (elective and emergency) between January 1st, 2004, to December 31st, 2023. Methods Incidence and prevalence data were obtained from the validated Lothian IBD Registry. We identified patients who commenced an advanced therapy using multiple administrative databases, and identified patients who underwent colectomy using the NHS Lothian pathology database, TrakCare theatre lists, NHS Lothian multidisciplinary meetings database, and an inpatient coding database. We collected data by manual review of the electronic health records using the TrakCare (InterSystems Corporation, Cambridge, Massachusetts, USA) system. We used SPSS Version 25 [IBM Inc., Chicago, IL, USA], Prism Version 10.0 [Graphpad Software, San Diego, CA, USA], and R 4.4.0 [R Core Team, Vienna, Austria] for statistical analyses and generation of graphs. We report advanced therapy prescription and colectomy data as both raw numbers and annual incidence rates. Results The prevalence of UC increased from 216 to 441 patients per 100 000 population in the twenty years from 2004, culminating in a total of 4115 patients with UC in 2023 (total Lothian population 1 million). We identified 617 patients who had received an advanced therapy (Table 1). Rates of first line advanced therapy increased from 0 per 100 UC patients in 2004 to 5.15 in 2023 (Figure 1). At the conclusion of 2023, 43%, 20%, 9%, and 3% of the advanced therapy exposed patients had received second, third, fourth, and fifth-line advanced therapy, respectively. We identified 559 patients of the prevalent UC population who had a colectomy, of which 68% were emergency colectomies. Absolute colectomy numbers decreased from 42 in 2004 to 7 in 2023, equating to 2.48 and 0.22 per 100 UC patients. We observed that 66% (339/559) of colectomies occurred in patients with extensive disease (E3), with 68% (355/523) performed for acute severe UC, of which 32% (114/355) occurred within 90 days of diagnosis. A total of 4% (22/559) of colectomies were for cancer (n=14) or dysplasia/suspected cancer (n=8). Colectomies for "chronic active UC refractory to medical treatment" have almost completely disappeared with only 5 colectomies performed for this indication in the last 2 years of follow-up. Conclusion We found the incidence of colectomy in the UC population progressively decreased over time, and correlated with an increased use, and number, of available advanced therapies.

DOP101 Maintaining remission after an episode of steroid-responsive Acute Severe Ulcerative Colitis: what is the best strategy?

Abstract Background The best maintenance therapy after a steroid-responsive acute severe ulcerative colitis (ASUC) episode remains poorly studied and is not addressed in current guidelines. We aimed to compare the impact of different treatment strategies following hospitalization for steroid-responsive ASUC. Methods Multicentric, multinational, retrospective cohort study including patients hospitalized with ASUC, between 2010-2021, who responded to intravenous steroids (Oxford Criteria). Patients were categorized according to treatment instituted after discharge - 5ASA, immunomodulators (IMM) and advanced therapy (AT). AT was considered as the reference for comparison. Our primary outcome was a composite of time until disease progression (need for steroids, need for therapy change, new hospitalization or colectomy); secondary outcomes were each event analyzed separately. Survival analysis and multivariate cox regression were performed. Results 271 steroid-responsive patients from 19 countries were included; median-age at diagnosis was 33 (IQR 25-48) years, 49% were male, 49% had extensive colitis at diagnosis; median disease duration was 26 (IQR 3.0-92.3) months. Following hospitalization for steroid responsive ASUC, 34% of patients received 5-ASA as a maintenance therapy, 23% IMM and 43% AT. During a median follow up of 59 months (IQR 38-92), 68% had disease progression: new course of steroids was needed in 40%, therapy change in 54%, new hospitalization in 33% and colectomy in 10%. In univariate analysis, patients treated with 5-ASA had a trend towards earlier disease progression, compared to AT (HR 1.37, CI 95% 0.99-1.91, p=0.06), earlier need for steroids (HR 1.70, CI 95% 1.11-2.59, p=0.014) and therapy change (HR 1.68, CI 95% 1.15-2.43, p=0.007). In multivariate analysis, adjusting for age and disease extension at diagnosis, disease duration, use of AT prior to ASUC hospitalization, and period of hospitalization (2010-2015 vs 2016-2021), patients treated with 5-ASA had a higher risk of disease progression compared to both IMM (HR 1.50, CI 95% 1.02-2.21, p=0.041) and AT (HR 1.86, CI 95% 1.26-2.74, p=0.002) – Figure 1. No differences were seen between IMM and AT in uni- and multivariate analysis. Shorter disease duration (HR 0.99, CI 95% 0.99-0.99, p=0.007), and prior use of AT (HR 1.67, CI 95% 1.13-2.47, p=0.010) were also associated with higher risk of disease progression – Table 1. Conclusion After an episode of steroid-responsive ASUC, shorter disease duration and prior use of advanced therapy were risk factors for disease progression. Approximately 1/3 of patients was treated with 5ASA alone. This strategy was also associated with a higher risk of poor outcomes and should be avoided.

P1020 Trends in Opioid Use among Patients with Inflammatory Bowel Disease and Changes Following Advanced Therapy Initiation: A Korean nationwide population-based study

Abstract Background Opioid use patterns among Asian patients with inflammatory bowel disease (IBD), and the impact of advanced therapy (AT) on opioid use, are not well understood. This study aimed to investigate trends in chronic opioid use and assess the impact of AT initiation on opioid use among Korean patients with IBD. Methods Data were extracted from the Korean Health Insurance Review and Assessment Service database for adult patients with IBD from 2010 to 2022. Chronic opioid use was defined as ≥90 days or ≥3 opioid prescriptions within a calendar year. Chronic opioid users were matched with non-chronic opioid users at a 1:3 ratio based on sex, age, and type of IBD. Analyses included Poisson regression, the McNemar test, and generalized estimating equation (GEE). Results Between 2010 and 2020, Chronic opioid use was more prevalent in patients with Crohn’s disease (CD) compared to those with ulcerative colitis (UC). The number and proportion of chronic opioid users among Korean patients with CD and UC increased significantly (p-values &amp;lt;0.0001 for both trends). In 2010, only 123 patients with CD (1.57%) and 113 patients with UC (0.54%) were classified as chronic opioid users. However, by 2020, these numbers rose sharply to 1,286 patients with CD (5.44%) and 1,087 patients with UC (1.97%). In the McNemar test, the number of opioid users significantly decreased following AT initiation (p-value &amp;lt;0.0001 for both CD and UC): a large number of patients discontinued opioids after initiating AT (1,639 patients with CD and 1,600 patients with UC), while only a small number of patients began opioids after initiating AT (681 patients with CD and 642 patients with UC). GEE analysis further demonstrated that AT was significantly effective in reducing the number of opioid users among patients with CD (odds ratio [OR] = 0.479, 95% confidence interval [95% CI] = 0.440–0.521, p-value &amp;lt;0.0001) and UC (OR = 0.844, 95% CI = 0.775–0.919, p-value = 0.0001). Conclusion Although opioid use among Korean patients with IBD has been on the rise, AT is effective in reducing the number of opioid users among patients with both CD and UC.

P1340 Gut microbiota changes are associated with type of advanced therapy in patients with Inflammatory Bowel Disease: baseline data from the Australian IBD Microbiome study

Abstract Background Gut microbiota are associated with both disease course and treatment outcomes in inflammatory bowel disease (IBD)1. This study aimed to characterise differences in gut microbial signatures according to medication use in the Australian IBD Microbiome (AIM) study2. Methods Faecal and oral samples alongside participant characteristics were collected at baseline from all patients with IBD enrolled in the AIM study from June 2019 to November 2023. Faecal and oral microbial samples were collected in DNA stabilising buffer, aliquoted and stored at -80oC. Samples underwent 16S rRNA sequencing with annotation of DNA sequences to operational taxonomic units at the genus level. Differences in alpha diversity (Shannon index) and relative abundance of observed genera between medication groups were assessed using Mann-Whitney U and Kruskal-Wallis tests. Beta diversity (Bray-Curtis dissimilarity) between bacterial communities were shown using the Principal Coordinate Analysis (PCoA), and significance of variance tested using ADONIS within R. Results 446 participants (232 CD, 214 UC) returned baseline faecal (n = 403) and/or oral samples (n = 436) with patient and disease characteristics presented in Table 1. No differences in faecal calprotectin were observed between patients on advanced therapy vs. patients who were not, nor between each advanced therapy class. Patients on advanced therapy had lower alpha diversity (p = 0.003) and distinct beta diversity (R2 0.64, p = 0.002) than those not on advanced therapy. Patients on anti-TNF therapy had lower alpha (p &amp;lt; 0.001) and distinct beta diversity (R2 1.75, p = 0.008) compared to patients on no advanced therapy (Figure 1AB). Alpha diversity remained lower when comparing those on either infliximab (p = 0.008) or adalimumab (p = 0.012) to patients on no therapy. There were no differences in alpha or beta diversity between other advanced therapy classes, between types of immunomodulator and between patients on 5-ASA compared to patients who were not. Pairwise comparisons between patients on no therapy and each class of advanced therapy demonstrated significantly different relative abundances of multiple genera observed in faecal samples (Figure 1C). No differences were observed in oral samples. Conclusion Distinct differences in both community structure and the relative abundance of multiple genera were observed in IBD patients according to type of advanced therapy despite no significant difference in biochemical activity. No microbiota differences were observed according to conventional 5-ASA or immunomodulator use. Future analysis including longitudinal samples and treatment outcomes may allow identification of unique microbial signatures predictive of treatment response.