Introduction

Etrasimod is an investigational, once-daily, oral, selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). In the ELEVATE UC 52 trial, primary and key secondary efficacy endpoints at Week 52 were evaluated among all patients randomised at baseline. The efficacy of etrasimod can be further characterised by evaluating efficacy endpoints at Week 52 among the subset of patients who met each efficacy endpoint at the end of the induction period (Week 12).

Aims & Methods

Here, we report proportions of patients receiving etrasimod that sustained induction efficacy endpoints at Week 52. In ELEVATE UC 52 (NCT03945188), patients (16–80 years) with moderately to severely active UC (defined as modified Mayo Score 4–9, endoscopic subscore ≥2 and rectal bleeding subscore [RBS] ≥1) were randomised 2:1 to once-daily etrasimod 2 mg or placebo. The ELEVATE UC 52 clinical trial comprised a 12-week induction period followed by a 40-week maintenance period with a treat-through design. This post hoc analysis assessed efficacy endpoints at Week 52 among the subset of patients who met the following efficacy endpoints at Week 12: clinical remission, endoscopic improvement, endoscopic improvement-histologic remission, symptomatic remission and RBS of 0.

Results

In ELEVATE UC 52, 81/289 (28.0%) patients treated with etrasimod achieved clinical remission at Week 12; of these, 66.7% (54/81) sustained clinical remission at Week 52 (Table). Among the 108/289 (37.4%) patients who achieved endoscopic improvement at Week 12, 72.2% (78/108) sustained the endpoint at Week 52; of 66/289 (22.8%) who achieved endoscopic improvement-histologic remission at Week 12, 63.6% (42/66) sustained the endpoint at Week 52; of 134/289 (46.4%) patients who achieved symptomatic remission at Week 12, 74.6% (100/134) sustained the endpoint at Week 52; of 166/289 (57.4%) patients who achieved an RBS of 0 at Week 12, 75.3% (125/166) sustained the endpoint at Week 52.

Conclusion

These findings suggest efficacy endpoints achieved at Week 12 were sustained by large proportions of etrasimod-treated patients at Week 52 based on both subjective and objective measures including clinical, endoscopic and histologic efficacy responses. Further analyses of larger samples sizes with longer follow-up are needed to evaluate long-term efficacy of etrasimod in patients with moderately to severely active UC.

Disclosure

BES: research/grants, e.g. Grant/Research Support: Arena, Janssen. Lecture fees/Speakers Bureau: BMS, Janssen, Lilly, Pfizer, Takeda. Consultancy, Advisory Committee/Board Member: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer-Ingelheim, BMS, Celltrion, Fresenius Kabi, Genentech, GSK, Janssen, Lilly, Merck, Pfizer, Prometheus Biosciences, Sun Pharma Global, Takeda Pharmaceuticals International, Teva Branded Pharmaceutical Products R&D. Shareholder/Stock Options: Ventyx Biosciences. Other non-financial support: Janssen, Lilly, Pfizer, Takeda.
SV: grant/research support: AbbVie, MSD, Pfizer, Galapagos, Takeda; consultancy/advisory: AbbVie, AbolerIS, Alimentiv, Arena, AstraZeneca, Avaxia, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Dr. Falk, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, Johnson & Johnson, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillotts, Zealand; lecture/speaker: AbbVie, Dr. Falk, Ferring, Hospira, MSD, Takeda, Tillotts.
MCD: grant/research support: Janssen; consultancy: AbbVie, Arena, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, Janssen, Pfizer, Prometheus, Takeda, Trellus Health, UCB; shares/royalties: Trellus; directorship/ownership interests: Trellus.
BGF: consultant/on advisory board: AbbVie, AbolerIS, AgomAB, AllianThera, Amgen, AnaptysBio, Applied Molecular Transport, Arena, Avoro Capital, Atomwise, BIOJAMP, Biora, Boehringer Ingelheim, Boxer, Celsius, Celgene/Bristol-Myers Squibb, Connect, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, FirstWord, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer, GSK, Hinge, HotSpot, InDex, Imhotex, Immunic, JAK, Janssen, Japan Tobacco., Kaleido, Landos, Leadiant, L.E.K., Lenczner Slaght, LifeSci, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic, Mylan, OM, Origo, Orphagen, Pandion, Pendopharm, Pfizer, Prometheus, Diagnostics, Play to Know AG, Progenity, Protagonist, PTM, Q32, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres, Silverback, Surrozen., Takeda, Teva, Thelium, TiGenix, Tillotts, Ventyx, VHSquared Ltd., Viatris, Ysios, YSOPIA, Zealand; speaker: AbbVie, Janssen, Takeda; Alimentiv Senior Scientific Director, provides central reading services; not a company employee, no equity stake; shareholder: Gossamer.
RP: research support: AbbVie, Janssen, Takeda, Pfizer; consultancy: Abbott, AbbVie, Abivax, Alimentiv, Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan, Organon, Pandion, Pendopharm, Pfizer, Progenity, Prometheus, Protagonist, Roche, Sandoz, Satisfai, Shire, Sublimity, Takeda, Theravance, Trellus, Viatris, Ventyx, UCB; speaker: AbbVie, Amgen, Arena, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, Takeda; member of advisory boards: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan, Organon, Pandion, Pfizer, Progenity, Protagonist, Roche, SandozShire, Sublimity, Takeda, Ventyx.
VJ: financial support: Celgene/Bristol-Myers Squibb, Pfizer, AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Takeda, Gilead and TiGenix; consultancy: AbbVie, Alimentiv, Amgen, Anokion, Applied Strategic, Arena, Asahi Kasei, Asieris, AstraZeneca, BIOJAMP, Celgene/Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, F Hoffmann La Roche, Flagship Pioneering, Fresenius Kabi, Fusion MD, Galapagos, Genentech, Gilead, GSK, Janssen, Knightslab, Organon, Landos, McKesson, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Prometheus, Protagonist, Reistone, Roche, Sandoz, Second Genome, Sorriso, Takeda, Teva, Topivert, Ventyx, Viatris, Vividion; lecture: AbbVie, Ferring, Galapagos, Janssen, Pfizer, Takeda, Bristol-Myers Squibb.
AJY: consultancy: Pfizer, Arena, Takeda, Bristol-Myers Squibb; lecture/speaker: Bristol-Myers Squibb.
MVC: grant support: Pfizer, Janssen, Novartis, Bristol-Myers Squibb; consultancy: AbbVie, Arena, Bristol-Myers Squibb, Medtronic, Pfizer, Prometheus, Eli Lilly, Janssen and Takeda; speaker: AbbVie, Janssen, Medtronic, Pfizer, Bristol-Myers Squibb, Takeda.
JP: personal: AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Galapagos, Genentech/Roche, GSK, Immunic, Janssen, Mirum, Morphic, Nestlé, Origo, Pandion, Pfizer, Progenity, Revolo, Takeda, Theravance and Wassermann; grant support: AbbVie, Pfizer.
MG: employee & shareholder of Pfizer AG.
CJR, PS, JW: employees & shareholders of Pfizer.
SG: financial support/grants: GSK; speaker: Janssen, AbbVie, Pfizer, Takeda, Eli Lilly, Celltrion; advisory board: Janssen, AbbVie, Takeda, Pfizer, Bristol-Myers Squibb, Gilead, Galapagos, Ferring; Steering Committee member: Janssen, Bristol-Myers Squibb, AbbVie; Drug Monitoring Committee member: Janssen.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the most common neoplastic disease of the pancreas with a high mortality rate due to late diagnosis at an advanced stage for its asymptomatic progression. Chronic pancreatitis, one of the risk factors for the development of PDAC, complicates the diagnostic process as both conditions sometimes share overlapping clinical and pathological features. Identifying individuals at higher risk of developing the disease and detecting pancreatic cancer at an early, curable stage is critical to improving overall patient outcomes. This study investigates the potential of relative telomere length (RTL) in peripheral blood and microbiome composition as biomarkers for PDAC. These biomarkers could support a minimally invasive liquid biopsy approach for early diagnosis of PDAC, differentiation from chronic pancreatitis, and screening of high-risk individuals.

Aims & Methods

A total of 239 participants were enrolled in the study and were divided into four groups: patients with PDAC (n = 36), chronic pancreatitis (n = 60), type II diabetes mellitus (n = 91) and cancer-free individuals (n = 52). Peripheral blood samples were collected to estimate relative telomere length using the multiplex monochrome qPCR method. Stool samples from a subset comprising chronic pancreatitis patients (n = 13), PDAC patients (n = 12), and healthy controls (n = 7) were analysed using 16S rRNA sequencing for metataxonomic analysis of the gut microbiome.

Results

Microbiome analysis revealed dysbiosis in a subset of patients, with an overrepresentation of bacterial species such as Prevotella copri and Akkermansia muciniphila in chronic pancreatitis and PDAC patients. A trend towards reduced microbial diversity was observed in PDAC patients, with changes in bacterial composition already detectable in chronic pancreatitis patients. No significant differences were found in RTL between the PDAC and cancer-free patient groups, and the only risk factors associated with changes were age, gender and smoking.

Conclusion

The pilot findings suggest a general trend towards reduced microbial diversity in PDAC patients, with alterations in bacterial proportions already observed in individuals diagnosed with chronic pancreatitis. These data ptovide a basis for the development of non-invasive diagnostic strategies to improve early detection and clinical outcomes for patients with PDAC. However, relative telomere length has not been shown to be a reliable biomarker.

References

Wu H, Zou WB, Zhou DZ, Gu YT, Liao Z, Li ZS. Longer Leukocyte Telomere Length is Associated With an Increased Risk of Chronic Pancreatitis. Pancreas. 2017;46(8):e65-e66. doi:10.1097/MPA.0000000000000887
Riquelme E, Zhang Y, Zhang L, et al. Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell. 2019;178(4):795-806.e12. doi:10.1016/j.cell.2019.07.008
Antwi SO, Petersen GM. Leukocyte Telomere Length and Pancreatic Cancer Risk: Updated Epidemiologic Review. Pancreas. 2018;47(3):265-271. doi:10.1097/MPA.0000000000000995
Campa D, Felici A, Corradi C, et al. Long or short? Telomere length and pancreatic cancer and its precursor lesions, a narrative review. Mutagenesis. 2025;40(1):39-47. doi:10.1093/mutage/gead034
Sexton RE, Uddin MH, Bannoura S, et al. Connecting the Human Microbiome and Pancreatic Cancer [published correction appears in Cancer Metastasis Rev. 2022 Jun;41(2):333. doi: 10.1007/s10555-022-10037-3.]. Cancer Metastasis Rev. 2022;41(2):317-331. doi:10.1007/s10555-022-10022-w

Introduction

Surgery is the traditional treatment of traumatic pseudocysts, but with considerable morbidity and mortality. A minimally invasive management of these collections has been increasingly used. Objective: To analyze the outcome following endoscopic treatment of pancreatic pseudocysts caused by abdominal trauma and to study the integrity of the main pancreatic duct (MPD).

Aims & Methods

Patients with pancreatic fluid collections due to abdominal trauma and who underwent endoscopic therapy were studied. All were symptomatic with a persistent collection for more than 6 weeks. Opacification of the MPD allowed characterization according to Takishima Classification (I, II and III) which guided therapy. Endoscopic drainage was divided into: transpapillary (Takishima II and III without bulging), transmural (type I) or combined (type II or III with bulging).

Results

From January 2020 January 2025 51 patients (36 men, mean age of 35.2 years, range - 13.9 years) were identified who developed pancreatic collections after blunt or penetrating abdominal trauma., The average size of the collection was 14.3  5.2 cm. ERP was obtained in 47/51 (90%). Drainage was transmural in 13 (all type I), combined in 24 (type IIa (4), IIb (7) and III (13) and transpapillary in 10 (all type III without bulging). The remaining 4 were drained transmurally. The success of endoscopic treatment was 94% with a recurrence rate of 8%. Stent occlusion occurred in 6%. There were 9 complications, but no procedural-related deaths. Patients with penetrating trauma had more recurrences than those with blunt trauma (p = 0.01). Penetrating trauma conferred a relative risk for development of infection 0.25; (95% 0.07 - 0.88; p = 0.045).

Conclusion

Endoscopic treatment of pancreatic fluid collections that develop after pancreatic trauma is safe and effective and can be considered a first-choice alternative to surgical and/or percutaneous treatment. Pancreatography is useful in determining the best endoscopic approach.

Disclosure

​NO CONFLICT OF INTEREST

Introduction

Lynch syndrome (LS) represents the most prevalent hereditary colorectal cancer (CRC) syndrome, with approximately one in 279 individuals in the general population believed to carry a pathogenic variant. This autosomal dominant condition results from germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM). In addition to colorectal cancer, LS encompasses various extracolonic malignancies, such as gastric carcinoma (lifetime risk of 13%) and small bowel cancer (lifetime risk of 8%). Both German and current NCCN guidelines advise upper GI screening using esophagogastroduodenoscopy (EGD) every 2-4 years. However, standard EGD screening often misses lesions in the jejunum, where up to one third of small bowel cancers occur. Consequently, we sought to determine the frequency of jejunal lesion detection with push enteroscopy employing a colonoscope and whether this method maintains the overall diagnostic quality.

Aims & Methods

Patients with a proven pathogenic mutation in a DNA mismatch repair gene were included in a surveillance program at our National Center of Hereditary Tumor Syndromes, where all patients are followed prospectively after signing an informed consent. We assessed endoscopic findings using standard esophagogastroduodenoscopy (EGD) compared to push enteroscopy using a pediatric colonoscope at our center. We implemented the routine use of push enteroscopy in August 2022. The same endoscope was used for the following colonoscopy. Results of endoscopy, histopathology, affected gene were compared.

Results

Between April 2013 and July 2022, a total number of 445 EGDs were performed in 187 patients (range 1-7; 108 (58%) female; median age at endoscopy 48 years), all carrying a pathogenic MMR gene variant (66 MLH1 (35.5%); 86 MSH2 (46%); 25 MSH6 (13%); 9 PMS2 (5%); 1 Epcam (0.05%)).
Between August 2023 and April 2023, a total number of 103 push enteroscopies using a colonoscope were performed in 103 carriers of a pathogenic MMR gene variant (54 (52%) female; median age at endoscopy 48 years; 38 MLH1 (37%); 46 MSH2 (45%); 11 MSH6 (11%); 4 PMS2 (4%); 1 Epcam (1%); 3 MLH1 and MSH2 (3%)).
Using standard EGD, Barrett esophagus was detected in 23 (5%) patients, with three patients exhibiting high-grade dysplasia, whereas push enteroscopy identified Barrett's esophagus in 4 (4%) patients and revealed one case of eosinophilic esophagitis. Helicobacter pylori infection was found in 21 (5%) and 4 (4%) cases, respectively. Intestinal metaplasia was detected in 49 (11%) patients with standard EGD and 23 (22%) patients with push enteroscopy, both revealing one case (MLH1) with dysplasia. Neoplastic and preneoplastic lesions observed included gastric cancer (5; 1%), gastric adenomas (7; 1.6%), duodenal cancer (3 duodenal, 2 ampullary cancers; 1%), and duodenal adenomas (8; 1.8%) with standard EGD, while no neoplastic lesions were found using push enteroscopy. However, push enteroscopy enabled the detection of three jejunal adenomas, including two advanced adenomas.

Conclusion

This prospective endoscopic study demonstrates that monitoring the upper gastrointestinal (GI) tract in Lynch syndrome (LS) patients yields clinically significant findings for a considerable proportion of individuals. The application of push enteroscopy does not impede the identification of pertinent lesions. Notably, we observed an increased detection rate of gastric intestinal metaplasia using this technique.