Introduction

The time from treatment initiation to symptom relief, including rectal bleeding (RB) and stool frequency (SF), is key for patients (pts) with ulcerative colitis (UC) and can help guide therapy decisions. 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 UC. Data from pt e-diaries can help inform on symptoms in pts with UC.

Aims & Methods

We present a post hoc analysis of daily e-diary data collected on RB and SF from pts enrolled in the ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) phase 3 clinical trials.¹ Data were pooled from the ELEVATE UC 52 and ELEVATE UC 12 studies, which randomised pts with moderately to severely active UC and an inadequate response or loss of response or intolerance to ≥1 approved UC therapy 2:1 to receive etrasimod 2 mg once daily or placebo (PBO). Daily Mayo RB and SF subscores (RBS and SFS) and partial modified Mayo score (pMMS; RBS + SFS) were calculated from pt e-diary responses, as well as change from baseline (CFB) during the first 28 days of therapy. Symptomatic responders were pts with ≥30% CFB (decrease) in pMMS. Symptomatic remission was defined as pts with RBS=0 plus SFS=0 or 1 (with ≥1‑point improvement from baseline). RB and SF remission were defined as pts with RBS=0 and SFS=0, respectively. The Mantel–Haenszel weighted test was used to assess the adjusted risk differences in proportions of responders between treatment groups.

Results

At baseline, pts receiving etrasimod and PBO had a mean (SD) RBS of 1.6 (0.69) and 1.6 (0.68), SFS of 2.4 (0.74) and 2.4 (0.74), and pMMS of 4.0 (1.07) and 4.0 (1.07), respectively. Adjusted differences in symptomatic response and symptomatic remission in pts receiving etrasimod vs PBO became significant from Day 2 (5.56 [0.79, 10.33]) and Day 11 (4.69 [0.36, 9.03]), respectively. Adjusted differences (95% confidence interval) in RB remission and SF remission in pts receiving etrasimod vs PBO reached significance from Day 15 (6.33 [0.14, 12.51]) and Day 3 (3.51 [0.87, 6.14]), respectively (all p<0.05; Table).

Conclusion

In this post hoc analysis of the phase 3 ELEVATE trials, we found significant, early improvements in UC symptoms in pts receiving etrasimod vs PBO beginning within 2 days. These findings indicate a potentially rapid onset of symptomatic effect with etrasimod treatment.

References

1. Sandborn WJ et al. Lancet 2023: Epub ahead of print

Disclosure

MCD: consultancy fees: AbbVie, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Genentech, Gilead Sciences, Janssen Pharmaceuticals, Pfizer Inc, Prometheus Laboratories, Takeda, Trellus Health, UCB; received grant/research support: Janssen; shares/royalties in Trellus Health; directorship/ownership interests in Trellus Health.
SV: lecture/speaker fees: AbbVie, Dr. Falk Pharma, Ferring Pharmaceuticals, Hospira, MSD, Takeda, Tillotts; consultancy/advisory fees: AbbVie, AbolerIS, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Dr. Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, Gilead Sciences, Hospira, Imidomics, Janssen, Johnson & Johnson, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer Inc, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance Biopharma, Tillotts, Zealand Pharma; grant/research support: AbbVie, MSD, Pfizer Inc, Galapagos, Takeda.
MC: grant support: Galapagos, Janssen, Pfizer Inc; consultancy fees: Eli Lilly, Gilead Sciences, Janssen, Pfizer Inc, Takeda, Tillotts; investigator: AbbVie, Boehringer Ingelheim, Celgene, F Hoffmann La Roche, Genentech, Hospira, Janssen Cilag International LV, Janssen Cilag International NV, Millenium Pharmaceuticals, Shield, Shire, Takeda; Principal Investigator: AbbVie, Ferring Pharmaceuticals, Janssen, MSD, Takeda.
PMI: grant support: Celltrion, Janssen, MSD, Takeda; lecture fees: AbbVie, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, Janssen, MSD, Pfizer, Sapphire Medical, Sandoz, Shire, Takeda, Tillotts, Warner Chilcott; advisory fees: AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Genentech, Gilead Sciences, Hospira, Janssen, MSD, Pfizer, Pharmacosmos, Prometheus, Roche, Sandoz, Samsung Bioepis, Takeda, Topivert, VH2, Vifor, Warner Chilcott.
LB, JCW, CJR, WW: employees and shareholders of Pfizer Inc.
MG: employee and shareholder of Pfizer AG.
JT: advisory board fees: AbbVie, Arena Pharmaceuticals, Bristol-Myers Squibb, Galapagos, Janssen and Pfizer Inc; research grants: AbbVie and Janssen; speaker fees: AbbVie, Galapagos, Janssen, Pfizer Inc.
RP: consultancy fees: Abbott, AbbVie, Abivax, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, BIOJAMP, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, GSK, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma, Trellus, Viatris, Ventyx Biosciences, UCB; speaker fees: AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring Pharmaceuticals, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, Takeda; advisory boards: AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, BIOJAMP, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring Pharmaceuticals, Fresenius Kabi, Genentech, Gilead Sciences, GSK, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda, Ventyx Biosciences; research support: AbbVie, Janssen, Takeda, Pfizer.

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

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

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.