Introduction

Mirikizumab is a humanized immunoglobulin G4 monoclonal antibody against the p19 subunit of interleukin-23, a key inflammatory mediator in ulcerative colitis (UC). Mirikizumab demonstrated an acceptable safety profile, clinical response, clinical remission, and endoscopic remission in the pediatric SHINE-1 study. Here we describe patient-reported outcomes in pediatric patients with moderate to severe UC from the phase 2 SHINE-1 study (NCT04004611) following 52 weeks of mirikizumab treatment.

Aims & Methods

Patients aged 2 to <18 years with active UC who had an inadequate response, loss of response, or intolerance to corticosteroids, immunosuppressants, or biologic therapies, or had corticosteroid-dependent colitis, were included in the study. Patients weighing >40 kg received an induction dose of mirikizumab 300 mg via intravenous infusion; patients weighing ≤40 kg received mirikizumab 5 or 10 mg/kg via intravenous infusion at weeks 0, 4, and 8. At week 12, patients were assessed for clinical response using the Modified Mayo Score. Responders entered a maintenance period and received subcutaneous doses of mirikizumab at 200 mg (>40 kg), 100 mg (>20 kg to ≤40 kg), or 50 mg (≤20 kg) once every 4 weeks, with the last patient visit at week 52. Abdominal Pain Numeric Rating Scale (NRS), Urgency NRS, and Fatigue NRS scores were assessed through 52 weeks.

Results

Responders (69.2%, n=18/26) reported improvements in Abdominal Pain NRS, Urgency NRS, and Fatigue NRS scores through all age groups compared to baseline at week 52 (Table 1). A ≥30% improvement in the Abdominal Pain NRS was observed in 50% (n=7) of patients aged 12 to <18 years who scored ≥3 at baseline (N=14).

Table 1.

Conclusion

Mirikizumab demonstrated improvements in abdominal pain, bowel urgency, and fatigue following induction and maintenance treatment. These results provide supporting evidence for the pivotal phase 3 pediatric study SHINE-2 and suggest important improvements in quality of life.

Disclosure

M. Dubinsky has received honoraria as a consultant for: AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, F. Hoffmann-La Roche, Genentech, Gilead Sciences, Janssen, Pfizer, Prometheus Therapeutics and Diagnostics, Takeda, and UCB Pharma; has been contracted for research by: AbbVie, Janssen, Pfizer, and Prometheus Biosciences; has stock interest in: Trellus Health; and has received licensing fees from: Takeda; J. L. Kaplan has nothing to disclose; A. Bousvaros has received research support from: AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, BUHLMANN Diagnostics, Eli Lilly and Company, Janssen, ProciseDx, and Takeda; was a consultant for: Best Doctors, Eli Lilly and Company, Fresenius Kabi, and Takeda; and has received honoraria and royalties from: Boston University and UptoDate; D. Turner has received consultation fees, research grants, royalties, and/or honoraria from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Ferring Pharmaceuticals, Janssen, Pfizer, Prometheus Biosciences, Roche, Shaare Zedek Medical Center, Shire, Sorriso Pharmaceuticals, Takeda, The Hospital for Sick Children, and Thermo Fisher Scientific; T. Hunter Gibble, W. J. Komocsar, A. Larkin, J. Johns, X. Zhang, and W. Crandall are employees and shareholders of: Eli Lilly and Company; J. Hyams is on the advisory board for: Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, and Janssen; and was a consultant for: AbbVie, Pfizer, and Takeda.

Introduction

Intraductal Papillary Mucinous Neoplasm (IPMN) is the most frequent type of pancreatic cystic neoplasm found in the general population. Due to the advances in imaging technologies, the rate of detection of pancreatic cystic neoplasms has been increasing in the past years. A large-scale single-center cohort study conducted in Seoul revealed a prevalence of 1.7% in asymptomatic healthy individuals [1]. Polycystic liver disease (PLD) is a rare disorder characterized by the presence of at least 10 parenchymal cysts in the liver. It may be inherited in an autosomal dominant fashion and, depending on the most prominent phenotype, PLD can be an isolated manifestation in autosomal dominant polycystic liver disease (ADPLD) or it can be an extrarenal manifestation in autosomal dominant polycystic kidney disease (ADPKD) [2,3]. In ADPKD, cysts can be detected also in the pancreas, seminal vesicles and arachnoid membrane [4]. In literature there are isolated reports of association between Intraductal Papillary Mucinous Neoplasm and Autosomal Dominant Polycystic Kidney Disease [5,6].

Aims & Methods

A retrospective observational study was conducted to include all PLD patients followed at CEMAD (Centro Malattie Apparato Digerente) Fondazione Policlinico Universitario A. Gemelli to determine the prevalence of IPMNs in PLD patients (isolated or associated to ADPKD) using abdominal resonance imaging (MRIs) and/or abdominal CT scan, in order to evaluate whether IPMN can be a not acknowledged manifestation of PLD.

Results

Abdominal MRIs and/or abdominal CT scans were examined for 92 PLD patients (56 ADPKD and 36 isolated PLD). IPMNs were detected in 8 patients (8.7% of total), 4 with isolated PLD (11.7% of total isolated PLD patients) and 4 with PLD in ADPKD (7% of total ADPKD patients). As for the IPMN site, body-tail localization of the IPMN was the most frequent detected (50% of total IPMNs).

Conclusion

A high prevalence of IPMN in PLD patients was found, which seems to be higher than prevalence found in the general population (8.7% vs 1.7%). Moreover, IPMN appeared to be more frequent in isolated PLD than in PLD associated with ADPKD (11.1% vs 7%). Our results suggest we should consider the possibility of IPMN being another extrahepatic manifestation of PLD. Of course, further studies in a larger population of patients are needed in order to confirm our findings.

References

References:

1. Chang YR, Park JK, Jang JY, Kwon W, Yoon JH, Kim SW. Incidental pancreatic cystic neoplasms in an asymptomatic healthy population of 21,745 individuals: Large-scale, single-center cohort study. Medicine (Baltimore). 2016 Dec;95(51):e5535.

2. Lesioni benigne epatiche 2022: linea guida multisocietaria per la pratica clinica

3. EASL Clinical Practice Guidelines on the management of cystic liver diseases. J Hepatol. 2022 Oct;77(4):1083-1108. doi: 10.1016/j.jhep.2022.06.002. Epub 2022 Jun 18. Erratum in: J Hepatol. 2023 Nov;79(5):1338.

4. Harris PC, Torres VE. Polycystic Kidney Disease, Autosomal Dominant. 2002 Jan 10 [updated 2022 Sep 29]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024.

5. Sato Y, Mukai M, Sasaki M, Kitao A, Yoneda N, Kobayashi D, Imamura Y, Nakanuma Y. Intraductal papillary-mucinous neoplasm of the pancreas associated with polycystic liver and kidney disease. Pathol Int. 2009 Mar;59(3):201-4.
   

6. Naitoh H, Shoji H, Ishikawa I, Watanabe R, Furuta Y, Tomozawa S, Igarashi H, Shinozaki S, Katsura H, Onozato R, Kudoh M. Intraductal papillary mucinous tumor of the pancreas associated with autosomal dominant polycystic kidney disease. J Gastrointest Surg. 2005 Jul-Aug;9(6):843-5.

Introduction

Short bowel syndrome (SBS) is the most common cause of intestinal failure (IF) in children and is generally managed using parenteral nutrition and/or intravenous fluids (PN/IV). Long-term PN/IV can cause potentially life-threatening complications. Patients may receive teduglutide (TED) to encourage adaptation of the remaining intestine and to reduce dependence on PN/IV. Short-term studies have shown that TED is effective and has an acceptable safety profile in children and adults with SBS-associated IF (SBS-IF). However, assessment of long-term treatment with TED in paediatric patients with SBS-IF is limited.

Aims & Methods

We report real-world long-term safety and effectiveness data of TED from a paediatric cohort enrolled in the prospective, multinational SBS Registry (NCT01990040; EUPAS7973). Data were analysed cumulatively for up to 6 years between enrolment and interim data cut-off (June 23, 2014 to June 30, 2023). Patients were categorised based on whether they received TED (ever-treated; received ≥1 dose of TED 0.05 mg/kg/day [median]) or never received TED (never-treated; received PN/IV for ≥6 months before study entry). Safety endpoints included: occurrence of colorectal cancer in patients with any remnant colon; other malignancy; colorectal polyps; and adverse events (AEs). Effectiveness endpoints included clinical response (≥20% reduction in PN/IV volume from baseline) and change from baseline in volume of PN/IV (per weight [L/kg]) and number of days/week receiving PN/IV.

Results

In total, 398 paediatric patients were enrolled: 266 never-treated, 132 ever-treated (per-protocol set, n=397; 266 never-treated, 131 ever-treated). Patients had a mean (standard deviation [SD]) age of 5.4 (4.01) years (ever-treated 6.8 [4.12] years; never-treated 4.8 [3.80] years) and the majority were male (63.7%; ever-treated 68.7%; never-treated 61.3%). The median (range) length of exposure in ever-treated patients was 29.0 (1.15–106.61) months.
No new cases of colorectal cancer or new/worsening colorectal polyps were reported between baseline and interim cut-off. New/worsening malignancies were reported for one never-treated patient. A greater proportion of ever-treated patients reported AEs (87.0% vs 74.4%) and serious AEs (SAEs; 72.5% vs 59.0%) than never-treated patients. AEs and SAEs related to TED were reported in 15.3% and 6.1% of ever-treated patients, respectively. There were no allergic or hypersensitivity reactions to TED. The most common TED-related AEs were vomiting (3.8%) and abdominal pain (2.3%). Fatal events were recorded for one ever-treated and three never-treated patients.
A greater proportion of ever-treated patients had achieved a clinical response (year 1, 18/30, 60.0%; year 3, 11/17, 64.7%) than never-treated patients (year 1, 23/100, 23.0%; year 3, 17/82, 20.7%). Ever-treated patients had a greater mean (SD) reduction from baseline in PN/IV volume (L/kg; ever-treated: year 1, −39.4% [35.97], n=19; year 3, −61.6% [23.64]; n=7; never-treated: year 1, −21.1% [50.70], n=80; year 3, −34.4% [36.83], n=49) and number of days/week receiving PN/IV (ever-treated: year 1, −1.6 [2.16], n=30; year 3, −1.5 [1.77], n=17; never-treated: year 1, −1.0 [2.22], n=100; year 3, −0.6 [1.51]; n=82) than never-treated patients.

Conclusion

This 6-year interim analysis of real-world data from a large cohort of paediatric patients with SBS-IF supports that the safety profile of TED is consistent with the previous 5-year follow-up and suggests that TED improves intestinal adaptation in paediatric patients with SBS-IF over a 3-year period.

Disclosure

Palle B Jeppesen: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; commercial relationships as consultant and speaker with Albumedix, ArTara Therapeutics, Baxter, Coloplast, Ferring Pharmaceuticals, Fresenius Kabi, GLyPharma Therapeutic, Ironwood Pharmaceuticals, Naia Pharmaceuticals, NorthSea Therapeutics, Novo Nordisk Foundation, Protara Therapeutics, Takeda, Therachon, VectivBio and Zealand Pharma.
Martina Kohl-Sobania: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; study investigator for NPS Pharmaceuticals and Takeda; honoraria from Aposan, Takeda and Tauro-Implant as a speaker; advisory board member for Takeda.
Francisca Joly: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; study investigator for NPS Pharmaceuticals, Takeda, VectivBio and Zealand Pharma; advisory board member for Alira Health, ArTara Therapeutics, Baxter, M3E Solutions, Takeda, Therachon, VectivBio and Zealand Pharma; commercial relationships as consultant and speaker for Baxter, B. Braun, Fresenius Kabi, Nestlé Health Sciences, Takeda, Therachon and Théradial.
Joel B Mason: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; research support from Takeda as a site for the study; compensation from Care/of, a producer of nutritional supplements; honoraria from UpToDate, a web-based medical information platform, for authoring chapters.
Johane P Allard: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; fees from Takeda as a consultant and speaker, and research support from Takeda as a study site principal investigator (PI); research support from Fresenius Kabi and OMS as a PI; honoraria from Baxter as a speaker and consultant; research support from Zealand Pharma as a site PI.
Ulrich-Frank Pape: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; honoraria from Takeda as a consultant and speaker, and research support from Takeda, VectivBio and Zealand Pharma as a study site PI.
Loris Pironi: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; advisory board member for Baxter, NorthSea Therapeutics and Takeda.
Gabriel E Gondolesi: speaker for Takeda; compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; received investigator-initiated research grant from Takeda.
Lauren K Schwartz: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; speaker for Bristol Myers Squibb; advisory board member for Takeda.
Pinggao Zhang, Sasan Sabrdaran and Yi Wen Huang: employees of Takeda Pharmaceuticals U.S.A., Inc. and receive stock and/or stock options.
André Gabriel: former employee of Takeda Pharmaceuticals U.S.A., Inc. who received stock and/or stock options.

Acknowledgements: This study was funded by Takeda Pharmaceuticals U.S.A., Inc., MA, USA. Medical writing support, funded by Takeda Pharmaceuticals U.S.A., Inc., was provided by Elizabeth Coe, PhD of PharmaGenesis Cardiff, Cardiff, UK.

Introduction

The recommended treatment for severe complications of portal hypertension (PH) is transjugular intrahepatic portosystemic shunt (TIPS) implantation. Despite alcohol-related liver disease (ALD) representing the most frequent cause of advanced chronic liver disease (ACLD) and PH, literature on the effects of ongoing alcohol use (AU) after TIPS placement currently remains scarce.

Aims & Methods

The study population consisted of patients with ALD-related ACLD who had undergone TIPS implantation at two Viennese tertiary care centers (pooled cohort from the prospective AUTIPS study, NCT03409263: 01/2017-11/2022; and a retrospective cohort: 09/2000-09/2019). Through the electronic patient management system, individual demographic, laboratory, and clinical data were retrieved. AU after TIPS placement was investigated according to clinical documentation, serum ethanol quantification if available, and patients' reporting.

Results

Overall, the study population consisted of 276 patients (median follow-up 29 [IQR 54] months), 196 (71.0%) of which had received TIPS for refractory ascites while in 80 (29.0%) the indication for TIPS implantation had been variceal hemorrhage. The median age was 56 (IQR 13) years and 215 (77.9%) of the patients were men. At the time of the TIPS insertion, the median MELD was 11 (IQR 9) and 38 (13.8%) individuals were classified as Child-Pugh C. AU after TIPS placement was documented in 85 (30.8%) study participants. Baseline characteristics at TIPS implantation were similar in patients with and without post-TIPS AU, specifically regarding the prevalence of ascites (p=0.51), variceal hemorrhage (p=0.87), and hepatic encephalopathy (p=0.87).
Bacterial infections were more frequently detected among patients with ongoing AU (log-rank p=0.002). Importantly, patients with ongoing AU showed a higher incidence of acute-on-chronic liver failure (ACLF; log-rank p<0.001) and higher overall mortality (log-rank p=0.005; including liver-related death [log-rank p<0.001]).
Furthermore, cumulative incidence of ACLF (p=0.014) and liver-related death (p=0.004) were significantly higher in patients with ongoing AU. Of note, ongoing AU was independently associated with ACLF (asHR: 1.66; 95%CI: 1.13-2.44; p=0.010) and liver-related death (asHR: 2.09; 95%CI: 1.32-3.33; p=0.002) in multivariable competing risks regression analysis adjusted for age, MELD, and portal pressure gradient after TIPS implantation.

Conclusion

AU represents an independent risk factor for outcome deterioration after TIPS placement. These findings emphasize the paramount role of psychiatric care and harm reduction measures in addition to hepatological optimization after TIPS implantation.

Disclosure

C.S. received travel support from Gilead, Abbvie, Galapagos and Gebro; speaking honoraria from Abbvie and Gilead; and payments for consulting from Gilead.
M.S. received travel support from MSD, Sandoz, BMS, Abbvie and Gilead; and speaking honoraria from BMS.
M.J. received speaking honoraria from Abbvie and Gilead.
T.R. received grant support from Abbvie, Boehringer- Ingelheim, Gilead, MSD, Philips Healthcare, Gore; speaking honoraria from Abbvie, Gilead, Gore, Intercept, Roche, MSD; consulting/advisory board fee from Abbvie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Siemens; and travel support from Boehringer-Ingelheim, Gilead, and Roche.
M.M. served as a speaker and/or consultant and/or advisory board member for AbbVie, Bristol-Myers Squibb, Collective Acumen, Gilead, and W. L. Gore & Associates and received travel support from AbbVie, Bristol-Myers Squibb, and Gilead.
B.S. received travel support from AbbVie and Gilead.

Introduction

Inflammatory Bowel Disease (IBD), including Ulcerative Colitis (UC) and Crohn's Disease (CD), is a chronic gastrointestinal disorder marked by progressive inflammation. Recent therapies focus on a treat-to-target (T2T) strategy, as per STRIDE-II guidelines, aiming for defined short-term, intermediate-term, and long-term goals. While Western countries favor a top-down approach, emerging nations still largely follow the step-up method. Our study assesses the real-world effectiveness of the step-up strategy in meeting these targets at a tertiary care hospital in South India.

Aims & Methods

To study the short-term, intermediate-term and long-term treat-to-target goals (as per STRIDE-II recommendations) met, based on the current medical therapy in cases of Ulcerative Colitis and Crohn’s disease in a real world setting.
This study included 122 IBD patients (61 UC, 61 CD) treated with step-up approach of medical therapy over 18 months. Targets assessed included clinical response (short-term) at 4-8 weeks, biomarker normalization and clinical remission (intermediate-term) at 3 months, endoscopic remission and improvement in quality of life (long-term) at 6-9 months. Data on patient demographics, disease characteristics, therapeutic regimens, and adverse events were analysed using statistical methods.

Results

Short-term clinical response was achieved in 91.8% of UC patients and 86.9% of CD patients. Clinical remission was seen in 80.3% of UC and 70.5% of CD cases at 3 months. Biomarker normalisation was seen in 78.68% of UC and 68.85% of CD patients. Mucosal healing was observed in 31.2% of UC and 36.1% of CD patients at 6-9 months. Quality of life goals were met by 66% of UC and 67% of CD patients. Deep remission (clinical along with endoscopic remission) was achieved in 29.5% of UC and 32.8% of CD cases. Biologics and non-biologics showed no significant difference in achieving therapy goals. Baseline severity impacted outcomes, with severe UC patients struggling more to meet both short-term and long-term targets compared to those with milder forms (p<0.05). Similarly, mild and moderate CD patients achieved clinical remission better than severe CD patients (p<0.05). Multivariate analysis with logistical regression showed that in Crohn’s disease, baseline CDAI score predicted the likelihood of clinical remission (p=0.011). Baseline SES-CD score predicted the likelihood of achieving mucosal healing (p=0.045). Colonic CD was more likely to achieve mucosal healing than other sub-types (p=0.02). Sub-group analysis showed that elderly and pediatric populations, did not show statistically significant variations in treatment success.

Conclusion

Findings from our study suggest that the step-up approach can achieve outcomes that are broadly comparable to those reported in top-down studies from Western settings. While the top-down strategy is traditionally associated with early disease control, our results highlight that a carefully monitored and timely step-up approach can also be effective, particularly in real-world, resource-limited environments. These insights support the need for individualised treatment strategies that consider both disease severity and contextual healthcare factors.

References

Disclosure

Nil

Introduction

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a disease that complements Nonalcoholic Fatty Liver Disease (NAFLD) and is newly defined in 2020. It is defined based on metabolic abnormalities, regardless of the presence of liver disease caused by other causes such as alcohol consumption. Regarding the newly defined MAFLD, there has not been many studies related to the prevalence and risk factors in Korea, and no studies were found targeting soldiers, especially pilots.

Aims & Methods

The purpose of this study is to identify prevalence and risk factors for MAFLD in Korean air force army inclusive of pilots. The subjects are 1044 soldiers who underwent health checkups in Korean Air Force Aerospace medical center from January 2020 to December 2022. The data was retrospectively collected including age, height, weight, body mass index, waist circumference, blood pressure, smoking, drinking, exercise intensity, various blood test results, presence of fatty liver, and degree of fatty liver. Risk factors were analyzed using logistic regression.

Results

There were 667 pilots (64%) in our study, of whom 477 (72%) were high-performing pilots. The prevalence of MAFLD was 316 (30%) in all soldier. There was difference in the prevalence of MAFLD between pilot and non-pilot group (pilot group: 185 (28%), non-pilot group: 131 (35%) p-value=0.018). According to the multivariate analysis, body mass index (BMI), diabetes, systolic blood pressure, triglycerides (TG), uric acid (UA), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), alanine aminotransferase (ALT) were a risk factor associated with MAFLD among the entire soldiers. When categorized into pilot and non-pilot group, risk factors were associated with BMI, diabetes, alcohol consumption, and ALT in the non-pilot group. In the pilot group, they were statistically associated with age, BMI, dyslipidemia, TG, UA, HDL and ALT. Among them, UA showed the largest difference between the non-pilot group and the test group (non-pilot group: 1.14 (95% CI: 0.80-1.62), pilot group: 1.80 (95% CI: 1.38-2.36)).

Conclusion

There was a difference in the prevalence of MAFLD between pilot and non-pilot group. In particular, UA could be used to predict MAFLD as a specific risk factor in pilots comparing with non-pilots.