Introduction

Etrasimod is an investigational, oral, once-daily, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC).

Aims & Methods

We report efficacy and safety of etrasimod in patients (pts) with/without concomitant corticosteroid (CS) use at baseline (BL) of the ELEVATE UC phase 3 trials. In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), pts with moderately to severely active UC were randomised 2:1 to once‑daily etrasimod 2 mg or placebo (PBO). ELEVATE UC 52 used a treat-through design with a 12-week (wk) induction period followed by a 40-wk maintenance period. ELEVATE UC 12 had a 12‑wk induction period. At entry, pts were permitted to receive oral concomitant CS (prednisone [≤ 20 mg/day], budesonide [≤ 9 mg/day], or equivalent]) if on a stable dose for ≥ 4 wks prior to screening endoscopy; from Wk 12 CS tapering was recommended. Primary and secondary efficacy endpoints (defined in Table) and safety were assessed by BL concomitant CS status.

Results

In ELEVATE UC 52, 32.2% (93/289) and 29.2% (42/144) of etrasimod- and PBO-treated pts, respectively, were receiving CS at BL. In ELEVATE UC 12, 27.3% (65/238) and 29.3% (34/116) of etrasimod- and PBO-treated pts were receiving CS at BL. Among pts receiving CS at BL in ELEVATE UC 52, a higher proportion of etrasimod- vs PBO-treated pts achieved the endpoint of clinical remission (CR) at Wk 12 (p<0.05) and Wk 52 (p<0.001); this was also observed in pts not receiving CS at BL (p<0.001 at Wks 12 and 52; Table). In ELEVATE UC 12, a higher observed proportion of etrasimod- vs PBO-treated pts receiving CS at BL achieved CR at Wk 12 (p>0.05); a significant difference was observed in pts not receiving CS at BL (p<0.01). In both studies, similar results were observed across all secondary endpoints, with greater differences between etrasimod and PBO seen in pts not receiving CS at BL (Table). Across both ELEVATE trials, there were fewer serious adverse events and serious infections in the etrasimod arm in pts with CS at BL, than in those without CS at BL. In the PBO arms, the opposite was true.

Conclusion

Regardless of concomitant CS use at BL, etrasimod generally demonstrated efficacy at Wks 12 and 52, with greater treatment effect seen in pts without CS use at BL. No additional safety signal was apparent when etrasimod was initiated in combination with CS compared to without CS.

Disclosure

BES: financial support for 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.
KBG: research support: Celltrion, Galapagos, Pfizer Inc; speaker honoraria and/or consulting fees: AbbVie, Celltrion, Ferring Pharmaceuticals, Immunic Therapeutics, Janssen, Novartis, Pfizer Inc, Samsung Bioepis, Takeda, Tillotts.
DTR: grant support: Takeda, Helmsley Charitable Trust, GastroIntestinal Research Foundation; consultancy fees/is a member of advisory boards: AbbVie, AltruBio, ASLAN Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chronicles, Syneos, ClostraBio, Connect Biopharma, EcoR1, Genentech/Roche, Gilead Sciences, Iterative Health, Janssen Pharmaceuticals, Kaleido Biosciences, Eli Lilly, Pfizer Inc, Prometheus, Reistone, Seres Therapeutics, Takeda, Target RWE, Trellus Health; is on the Board of Trustees for Crohn’s & Colitis Foundation and Cornerstones Health, Inc; holds stock options in Alike Health, AltruBio, Datos Health and Iterative Health.
YL: speaker: Pfizer, Takeda, Abbvie, Jannsen; Consultancy, Advisory Committee/Board Member: Pfizer, BMS, Takeda, Abbvie, Amgen BioJamp, Lilly
JP: personal: AbbVie, Arena Pharmaceuticals, 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.
WW, KS, JCW, CCS: employees & shareholders of Pfizer Inc.
KW: employee & shareholder of Pfizer Canada Inc.
SS: speaker: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk, Fresenius, Janssen, MSD, Pfizer, Takeda; consultancy/advisory: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk, Fresenius, Gilead, IMAB, Janssen, MSD, Mylan, Pfizer Inc, Protagonist, Provention, Takeda, Theravance.

Introduction

Ustekinumab (UST) is a monoclonal antibody against the p40 subunit, common to IL-12 and IL-23 and was approved recently for the treatment of moderate to severe ulcerative colitis (UC).

Aims & Methods

The aim of this ongoing study is to report and analyze data from a large cohort of Greek patients with UC, who receive treatment with UST. We collected data from patients with UC from 14 Greek hospitals who commenced treatment with UST and evaluated their clinical response at week 16. Clinical response was defined as 50% reduction in the UC PRO2 values at week 16 compared to the values before treatment (baseline).

Results

Herein, we report the clinical outcomes at week 16, following the completion of induction regimen (i.v. loading 6mg/kg plus 1^st 90mg sc injection at week 8). The demographics and disease characteristics of the first 101 enrolled patients are shown in Table 1. The majority of patients (70, 70%) commenced treatment with UST due to active disease despite previous treatments. Seventy-six patients (76%) had been exposed to at least one biologic agent, most commonly anti-TNFs (54%). Thirty-eight (38%) and 29 (29%) patients were exposed to one and two biologics, respectively. Sixteen patients (16%) had previously received both infliximab (IFX) and vedolizumab (VDZ). Corticosteroids (50%) and mesalazine (5-ASA, 68%) were the most common concomitant treatments. UST was discontinued in 4 patients due to no response. A total of 79 patients have reached the 16^th week time-point, out of whom 61 have enough data to be analyzed. Analysis of the patients who had active disease at induction (total number with adequate data: 50) showed that clinical response was achieved in 36 (72%) and clinical steroid-free remission in 23 (46%) patients. In multiple logistic analysis concomitant use of 5-ASA was associated with a higher probability of clinical response at week 16 (P=0.009), while hemoglobin >13.1g/dL (P=0.047), and age >60 years (P=0.059) were associated with a lower probability of response. Seven patients were receiving concomitant corticosteroids at week 16.

Conclusion

In a real world clinical setting, UST was mostly used as a 2^nd or 3^rd line treatment for moderate to severe UC. At the end of induction treatment, the majority of patients showed clinical response and almost half were in steroid-free remission. Positive predictive factors of response to UST included the concomitant use of 5-ASA, while Hb >13.1 g/dl and age >60 years were associated with lack of response.
Funding: This study was funded through a research grant from the Greek IBD study group (EOMIFNE) to G.B. EOMIFNE grant: 2022EOMIFNEmp1

Disclosure

GB: Advisor/lecturer for Janssen, Pfizer, Takeda, Abbvie, MSD, Mylan, Genesis Pharma,
Adacyte Therapeutics, Amgen, Ferring, Cooper; Funding (Grants/Honoraria): Pfizer, Takeda,
Abbvie, Aenorasis; Research/Clinical Trials: Abbvie, Takeda.
EZ: Advisor/lecturer for Pfizer, Takeda, Abbvie, Amgen, Genesis Pharma, Aenorasis, Janssen
SM: Advisory/Lecturer for Pfizer, Takeda, Abbvie, Ferring, MSD, Janssen
GM: Advisor/lecturer for AbbVie, Celgene, Celtrion, Ferrirng, Genesis, Hospira, Janssen,
Millennium Pharmaceuticals, MSD, Mylan, Pharmacosmos, Pfizer, Takeda, VIANEX, Angelini,
Falk Pharma, Galenica, Omega Pharma; Consultancies for MSD and Takeda; Research support
from AbbVie, Galenica, Genesis, Menarini Group, MSD, Pharmathen.
KK: Advisor/lecturer for Abbvie, Aenorasis, Janssen, MSD, Pfizer and Takeda, Amgen, Ferring,
Galenica, Genesis Pharma.
MT: Advisor/lecturer for Janssen, Pfizer, Takeda, Abbvie, MSD, Mylan, Genesis Pharma,
Amgen, Research/Clinical Trials: AbbVie, Gilead, Takeda

Introduction

Ileocolonoscopy and Rutgeerts endoscopic score (RS) remains the gold standard to evaluate post-operative recurrence (POR) in Crohn's disease (CD). Intestinal ultrasound (IUS) is proposed as a non-invasive alternative for the diagnosis of POR, with a sensitivity of 89%, specificity of 86% and area under curve (AUC) of 0.93 (1). Bowel wall thickness (BWT) alone has a high accuracy in the diagnosis of POR and it is proposed that the association of other parameters such as hyperemia, loss of bowel wall stratification, involvement of mesenteric fat (i-fat) or ultrasound scores, increases sensitivity and specificity in the diagnosis of POR (2).

Aims & Methods

The aim of this study is to assess whether IUS parameters and ultrasound scores correlate with endoscopy in the diagnosis of POR. A unicentric retrospective study was performed. There were included patients with CD with both an ileocolonoscopy and intestinal ultrasound performed for the detection of POR, the time between tests was less than 6 months or there was no therapeutic change between tests.
Endoscopic POR was evaluated with Rutgeers score (RS), RS i0 and i1 was considered no POR and RS ≥i2a was POR. The IUS parameters were: BWT, Limberg Score, bowel wall stratification, inflammation of mesenteric fat, Simple US Score, SUS-CD and IBUS-SAS score.

Results

129 patients were included, baseline characteristics are in Table 1. In 108 patients (83.7%) the time between test was <6 months and in 21 (16.3%) >6 months without therapeutic changes. 38 (29.7%) were classified as endoscopic POR (RS i0 – i1) and 90 (69.8%) as POR: 28 (21.2%) i2a, 17 (13.3%) i2b and 45 (35.1%) severe (RS i3 – i4). With IUS, 42 patients (32.6%) were classified as no POR and 87 (67.4%) as POR. The mean BWT by IUS in patients without endoscopic POR was 2.6 mm (SD +/- 1.2) versus 4.8 (SD +/- 1.6) in patients with RS ≥i2a (p 0.001). BWT ≥3 had a sensitivity of 86.6%, specificity 78.9% and AUC of 0.83 in the diagnosis of POR. Hyperemia (Limberg ≥1) was present in 75 patients (84.3%) with RS ≥i2a versus in 8 patients (21.1%) without endoscopic POR (p 0.001). 21 patients (23.9%) of patients with RS ≥i2a presented loss of bowel wall stratification versus 0 (0%) with i0-i1 (p 0.001). I-fat was present in 16 patients (12.4%), all of them RS ≥i2a (p 0.02).
The mean results of IUS scores were: Simple Us score 5.6 (SD +/- 2.9), SUS-CD 2.1 (SD +/- 1.8) and IBUS-SAS 31.6 (SD +/- 23.3). In patients without endoscopic POR the mean result of Simple US Score was 3.0 (SD +/- 2.0) versus 6.7 (SD +/- 2.4) in RS ≥i2a (p>0.05). The mean result of SUS-CD without POR was 0.5 (SD +/ 1.0) versus 2.8 (SD +/- 1.5) in POR (p>0.05). In IBUS-SAS the mean result in RS i0-i1 was 13.4 (SD +/- 10.8) versus 39.2 (SD +/- 22.9) in RS ≥i2a (p>0.05). Simple US Score showed an AUC of 0.85 in the diagnosis of POR (95% CI 0.78 – 0.92), SUS-CD of 0.87 (95% CI 0.81 – 0.93) and IBUS-SAS of 0.85 (95% CI 0.77 – 0.92).

Conclusion

In our experience, IUS parameters such as BWT, Limberg score, loss of wall stratification, i-fat and IUS scores (IBUS-SAS, SUS-CD and Simple US Score), have a high accuracy in the diagnosis of POR.

References

1. Barchi, Alberto et al. “Recent advances in the use of ultrasound in Crohn's disease.” Expert review of medical devices vol. 20,12 (2023): 1119-1129. doi:10.1080/17434440.2023.2283166
2. Yung, Diana E et al. “Capsule Endoscopy, Magnetic Resonance Enterography, and Small Bowel Ultrasound for Evaluation of Postoperative Recurrence in Crohn's Disease: Systematic Review and Meta-Analysis.” Inflammatory bowel diseases vol. 24,1 (2017): 93-100. doi:10.1093/ibd/izx027

Introduction

Crohn’s disease (CD) is characterized by discontinuous inflammation. Failure to identify skipping lesions of the terminal ileum (TI) or transmural changes can lead to incorrect management.

Aims & Methods

Eligible adult patients with CD undergoing ileo-colonoscopy and computed tomography enterography (CTE) or magnetic resonance enterography (MRE) within six months. We determined the prevalence of endoscopic skipping (normal ileum on colonoscopy but proximal small bowel inflammation on cross-sectional imaging), skip lesions (discontinuous inflammation along the gastrointestinal tract identified on cross-sectional imaging), and penetrating complications.

Results

Among 202 patients, 45 (22.3%) had endoscopic skipping proximal to TI intubation. Fifty patients (24.5%) had small bowel skip lesions, primarily in the ileum. Strictures were identified in 34 patients (16.8%) through both imaging and ileo-colonoscopy, in 21 patients (10.4%) solely through cross-sectional imaging, and in 3 patients (1.5%) solely through ileo-colonoscopy. Approximately 63.8% of stricturing cases would be missed without cross-sectional imaging. Penetrating complications, including abscesses (2.5%) and various fistula types (4.9%), were detected in 15 (7.4%) patients.

Table. Comparison between patients who had active Crohn’s disease with and without abnormal TI on colonoscopy

Conclusion

Ileo-colonoscopy missed detection of active CD in approximately one-fifth of cases due to more proximal disease location. Stricturing disease would be missed in more than half of cases if cross-sectional imaging was not performed.

Disclosure

Virginia Solitano no conflict of interests.
Sudheer Kumar Vuyyuru has received consultancy fees from Alimentiv Inc.
Achuthan Aruljothy no conflict of interests.
Maan Alkhattabi has received consulting fees from Janssen. Speaker’s fees from Janssen, Takeda & Pfizer.
Melanie Beaton has received advisory board fees from AbbVie, Astra Zeneca, Gilead,
Janssen, Novo Nordisk, Lupin, Pfizer and Takeda.
Jamie Gregor has no conflict of interests.
Zahra Kassam has received Bayer Pharmaceuticals speaker honorarium and research grant, Fusion MD speaker fees, Alimentiv Inc consulting fees.
Rocio Sedano has received consultancy fees from Alimentiv Inc.
Harry Marshall has no conflict of interests,
Darryl Ramsewak has no conflict of interests.
Michael Sey has received consultant fees from Medtronic; Research grants and speaker fees from Pendopharm; Educational grant from Cook Medical.
Vipul Jairath has received consultancy/advisory board fees from AbbVie, Alimentiv Inc., Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert, Ventyx, and Vividion; and speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, and Fresenius Kabi.

Introduction

Autoimmune atrophic gastritis (AAG) leads to significant changes in the gastric mucosa, including hypo-achlorhydria and increased gastrin (G) levels, providing proliferative stimuli on the gastric mucosa (1-5).

Aims & Methods

The aim of our study is to evaluate the occurrence and characteristics of gastric polyps in AAG patients across six tertiary centers in Italy. We conducted a multicentric, cross-sectional study from January to June 2023, prospectively enrolling consecutive patients diagnosed with AAG, from January 2000 to June 2023, who underwent at least one endoscopy. Data on demographics, clinical history, biochemical profiles, serological data, and endoscopic and histopathological findings were collected.

Results

Among 612 AAG patients (73.9% female, median age 66) followed up for a median of 4 (IQR 2-7.5) years, 222 (36.3%) had at least one gastric polyp. Non-endocrine polyps (214) were found in 162 patients, including 151 (70.5%) inflammatory, 29 (13.6%) adenomatous, 18 (8.4%) fundic gland polyps, 13 (6.1%) adenocarcinomas, and one MALT lymphoma. Additionally, 108 patients (48.6% of the population with polyps and 17.6% of the overall AAG patients) presented with gastric neuroendocrine neoplasms (gNENs), 48 of whom also had non-endocrine polyps. The median polyp size was 4 (IQR 2-7) mm. Older age, smoking prevalence, and higher levels of G and chromogranin A (CgA) were associated with polyp presence. No significant differences in OLGA/OLGIM stages or H. pylori status were noted between patients with and without polyps.

Conclusion

This study represents the largest multicentric cohort of AAG patients, highlighting the significant presence of gastric polyps, including gNENs and various non-endocrine types including a not negligible proportion of patients who showed gastric adenocarcinoma. These results emphasize the importance of proactive endoscopic monitoring and comprehensive histopathological evaluation in patients with AAG, to effectively identify and manage these different gastric lesions.

References

1. Zhang H, Jin Z, Cui R, Ding S, Huang Y, Zhou L. Autoimmune metaplastic atrophic gastritis in chinese: a study of 320 patients at a large tertiary medical center. Scand J Gastroenterol. 2017;52(2):150-6.
2. Krasinskas AM, Abraham SC, Metz DC, Furth EE. Oxyntic mucosa pseudopolyps: a presentation of atrophic autoimmune gastritis. Am J Surg Pathol. 2003;27(2):236-41.
3. Kishino M, Nonaka K. Endoscopic Features of Autoimmune Gastritis: Focus on Typical Images and Early Images. J Clin Med. 2022;11(12).
4. Park JY, Cornish TC, Lam-Himlin D, Shi C, Montgomery E. Gastric lesions in patients with autoimmune metaplastic atrophic gastritis (AMAG) in a tertiary care setting. Am J Surg Pathol. 2010;34(11):1591-8.
5. Massironi S, Elvevi A, Gallo C, Laffusa A, Tortorella A, Invernizzi P. Exploring the spectrum of incidental gastric polyps in autoimmune gastritis. Dig Liver Dis. 2023.

Introduction

Walled-off pancreatic necrosis (WOPN) stands as a grave complication of acute pancreatitis, posing a substantial risk of sepsis-induced multiple organ failure when infected. Traditional surgical debridement, though effective, often entails elevated rates of adverse events and mortality. However, the emergence of endoscopic ultrasound (EUS)-guided cysto-gastrostomy employing LAMS presents a promising alternative for WOPN treatment, offering advantages in managing necrotic collections via endoscopic necrosectomy. This study aims to evaluate the technical and clinical success as primary objectives, alongside assessing adverse events and recurrence rates as secondary objectives.

Aims & Methods

We conducted a retrospective analysis of consecutive patients diagnosed with infected walled-off pancreatic necrosis (WOPN) and treated over a 48-month period from March 2020 to February 2024. The treatment protocol involved the placement of a novel LAMS – HOT AXIOS stent, utilizing an electrocautery-enhanced delivery system. This was followed by direct endoscopic necrosectomy (DEN), performed immediately post-stent deployment and repeated at intervals of 3 to 7 days until complete resolution was attained. All procedures were performed by expert clinicians under anesthesia with meticulous management of the necrotic cavity.

Results

31 patients diagnosed with infected WOPN underwent EUS assessment for LAMS placement. 5 patients were excluded: 3 due to cavity distance from gastric wall and 2 due to large amount of solid necrotic tissue (>30%). 26 patients underwent LAMS placement with average age 34.5 years. Drainage indications included sepsis with infected collection(53.8%), pain(23%), gastric outlet obstruction(11.5%), and a combination of these (11.5%). For primary LAMS insertion,100% technical success rate was achieved. Technical success rates for complete endoscopic necrosectomy were 30.8% & 69.2% at the end of 7 days & 14 days respectively. In cases of failed endoscopic necrosectomy, persistently infected necrosis, clinical deterioration, or complications, a step-up approach was pursued, leading to ultimately a surgical intervention in 23% (6 patients). Complications during endoscopic necrosectomy included transient self-limiting bleeding in 6 patients (23%), aspiration pneumonitis in 3 patients (11.5%), and spurting bleed from necrotic bed necessitating intra-procedural clip placement in one patient. Average procedure duration was 55 minutes with an average of 3 sessions required per patient. Clinical success, defined as pure endoscopic management without the need for surgical or radiological intervention, was achieved in 11 patients (42.3%). 6 patients (23%) required angioembolization, 6 patients (23%) required surgical intervention for incomplete drainage/sepsis and 3 patients(11.5%) required percutaneous catheter drain placement. Average hospital stay was 19 days. Patients who underwent successful endoscopic necrosectomy with LAMS were subjected to MRCP to identify disconnected ducts before LAMS removal, which occurred after an average duration of 18 days. Following stent removal, 11 patients (42.3%) required double pigtail plastic stent (5 Fr x 3 cm) placement due to disconnected ducts. Patients were followed up for an average of 60 days with no recurrences observed during this period.

Conclusion

Adoption of specialized LAMS and subsequent direct endoscopic necrosectomy produced commendable results in managing infected WOPNs. This approach showcased remarkable technical success and favorable clinical outcomes when executed according to established protocols in expert hands.