Introduction

Etrasimod is an oral, once-daily (QD), selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Etrasimod 2 mg QD improved bowel urgency (BU) at Weeks (Wks) 12 and 52 in the ELEVATE UC clinical programme.¹

Aims & Methods

We assessed associations between BU and efficacy endpoints, health-related quality of life (HRQoL) and biomarkers in patients receiving etrasimod in ELEVATE UC 52 (NCT03945188). BU was assessed at baseline (BL), Wk 12 and Wk 52 via a patient-reported, 11-point Urgency Numerical Rating Scale (NRS; 0–10; none to worst possible BU). We defined patient subgroups as with/without BU remission (NRS ≤ 1) or clinically meaningful improvement (CMI) in BU (NRS ≥ 3-point decrease from BL) at Wks 12 and 52. Associations were assessed between BU remission or CMI in BU (yes/no) and binary efficacy endpoints (multivariable logistic regression), change from BL in HRQoL using the inflammatory bowel diseases questionnaire total score and 36-item short form survey physical and mental component scores (multivariable linear regression) and faecal calprotectin (fCAL; Wilcoxon Rank test) at Wks 12 and 52.

Results

A larger proportion of patients with BU remission (73.6%) and CMI in BU (78.9%) at Wk 12 were naïve to biologic/Janus kinase inhibitors vs experienced. At Wk 12, significantly more patients with vs without BU remission met efficacy endpoints (odds ratio, OR [95% confidence interval, CI]: clinical remission 4.0 [2.3, 7.1]; endoscopic improvement 3.6 [2.1, 6.2]; both p < 0.0001) and had significantly greater improvement in HRQoL scores and lower fCAL (all p < 0.05; Table). A similar association was seen for CMI in BU at Wk 12 (OR [95% CI]: clinical remission 3.7 [2.1, 6.4]; endoscopic improvement 2.6 [1.6, 4.3]; both p < 0.001; Table) and for patients meeting BU outcomes at Wk 52.

Conclusion

Bowel urgency outcomes were associated with improvements in clinical and endoscopic endpoints, HRQoL scores and reduced fCAL at Wks 12 and 52. With etrasimod, BU outcomes may be surrogate markers of disease activity and HRQoL improvement.

References

1. Dubinsky MC et al. Am J Gastroenterol 2023; 118: S890–S891.
Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.

Disclosure

MCD reports consulting fees from AbbVie, Abivax, Arena Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Galapagos, Genentech, Gilead Sciences, Janssen Pharmaceuticals, Johnson & Johnson, Merck, Pfizer Inc, Prometheus Laboratories, Prometheus Biosciences, Sanofi, Sphyre, Takeda and UCB; Shareholder/ Royalties from Trellus Health, and has Directorship/Ownership interest in Trellus Health.
ERC reports speaker's bureau fees from AbbVie, Janssen, Eli Lilly, Takeda and Celltrion; and consulting fees from AbbVie, Janssen, Pfizer Inc, Takeda, Bristol Myers Squibb and Eli Lilly.
PMI reports grant fees from Celltrion, Janssen, MSD and Takeda; lecture fees from AbbVie, Bristol Myers Squibb, Celgene, Celltrion, Falk Pharma, Ferring, Galapagos, Gilead, MSD, Janssen, Pfizer Inc, Takeda, Tillotts, Sapphire Medical, Sandoz, Shire and Warner Chilcott; and advisory fees from AbbVie, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Genentech, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer Inc, Pharmacosmos, Prometheus, Roche, Sandoz, Samsung Bioepis, Takeda, Topivert, VH2, Vifor Pharma and Warner Chilcott.
MG and KL are employees of Pfizer AG and shareholders of Pfizer Inc.
AB is an employee of Pfizer Healthcare India Private Ltd and shareholder of Pfizer Inc.
GP is an employee of Pfizer Healthcare India Private Ltd
PH is an employee of Pfizer Inc; shareholder of Clene Nanomedicine, Haleon, Idorsia, Liquidia, Longboard Pharmaceuticals, Pfizer Inc, Proctor & Gamble; holds IP/Patents for US 2022/0257594 A1; and recieves grant/research support from AbbVie, Bristol Myers Squibb, Buhlmann, Janssen, Lilly, Pfizer Inc and Takeda.
CC is an employee and shareholder of Pfizer Inc.
KW is an employee of Pfizer Canada Inc and shareholder of Pfizer Inc.
RP receives consultancy fees from Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer Inc, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx and UCB; speaker's fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer Inc, Roche, Sandoz, Shire and Takeda Pharmaceuticals; is on the advisory boards for AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer Inc, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals and Ventyx; and receives research support from AbbVie, Janssen, Takeda and Pfizer Inc.

Introduction

Contemporary studies suggest there are racial disparities in the outcomes of acute presentations. This study aimed to investigate the impact of sex and race on the management and outcomes of patients presenting with upper gastrointestinal bleeding (UGIB).

Aims & Methods

Using International Classification of Diseases 10th Revision Codes, all adults >18 admitted from 2016–2020 with a discharge diagnosis of UGIB were extracted from the National Inpatient Sample.

Results

In over 900,000 hospitalisations for UGIB, 69.4%, 14.1%, 9.6%, 3.6%, 0.9% and 2.4% were for admissions in white, black, Hispanic, Asian/pacific islander, native American and ‘other’ patients respectively. Comorbidity burden varied between racial groups (p<0.001). White patients had higher crude rates of endoscopy, and comparable rates of surgery or interventional radiology to control blood loss, in comparison to other racial groups. Adjusted analysis revealed that black and Asian/pacific islander racial group patients had lower odds of in-hospital all cause mortality compared to white patients, but ‘other’ racial group patients had higher odds of mortality (p<0.001). There was no difference for Hispanic or native American patients. For non-variceal bleeding, these outcomes persisted. However, for variceal bleeds, there were no significant differences in outcomes between each racial group.

Conclusion

There are racial disparities in the management and outcomes of admissions for UGIB. These difference persist despite the aetiology of bleeding. Underlying reasons for differences in outcomes must be investigated to ensure improved outcomes across high-risk patient groups.

Introduction

Upper gastrointestinal bleeding (UGIB) is a major cause of mortality in the United States (US). This study aimed to investigate the contemporary trends in the management and outcomes of these patients as well as factors associated with in-hospital mortality, using national data.

Aims & Methods

The US National Inpatient Sample was queried from 2016-2020. Using International Classification of Diseases 10th Revision Codes, all adults >18 admitted with a principal discharge diagnosis of UGIB were extracted along with data about demographics, management and outcomes. Categorical variables were compared using chi-squared and expressed as percentages (%). Logistic regression was performed, adjusting for variables associated with adverse outcomes and reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Data were considered significant if p<0.001.

Results

There were 918,925 hospitalizations for UGIB in the study period. Variceal bleeding occurred in 36,050 (3.9%) of admissions. Endoscopy was performed in 451,450 (49.1%) of admissions, with 10,160 (1.1%) of admissions and 9,355 (1.0%) of admissions requiring interventional radiology and gastrointestinal surgery to control blood loss respectively. The crude rate of all-cause in-hospital mortality was 1.9%. Factors associated with death included variceal bleed (aOR 2.84 CI 2.67-3.02), age (aOR 1.03 CI 1.03-1.03), history of cancer (aOR 2.45 CI 2.35-2.56), ulcer disease (aOR 1.44 CI 1.39-1.49), chronic renal failure (aOR 1.34 CI 1.29-1.37), chronic obstructive pulmonary disease (aOR 1.29 CI 1.24-1.34), receipt of endoscopy (aOR 1.33 CI 1.29-1.38), surgery (aOR 3.92 CI 3.63-4.24) and interventional radiology (aOR 3.33 CI 3.09-3.58).

Conclusion

UGIB remains a significant cause of hospitalisation in the US. Knowledge of the contemporary trends and outcomes of this patient group is important to improve management in this at-risk patient group.

Introduction

The prevalence of adenoma in patients with positive fecal immunochemical tests (FIT) is shown to be higher. Increased adenoma detection and removal during colonoscopy have been shown to prevent CRC and interval cancers. However, there is considerable variation in the adenoma detection rate (ADR) among colonoscopies performed for FIT. We hypothesize that the ability of dye-based chromoendoscopy to stain the colorectal lesion and their borders and increase their contrast against the normal colorectal mucosa would enhance the detection of adenoma and non-polypoid colorectal neoplasms (NPCRN) in patients undergoing FIT positive colonoscopy. In this randomized control trial, we aim to compare the effectiveness of pan-colonic indigo carmine chromoendoscopy (PCC) to high-definition white light colonoscopy (WLC) in individuals undergoing colonoscopy for positive FIT test.

Aims & Methods

Patients undergoing colonoscopy after a FIT positive test were randomized 1:1 to undergo PCC or WLC. The study was conducted between January 2021 to May 2023 at the Singapore General Hospital, Singapore. Colonoscopy was performed by general and advanced endoscopists, and all received training on PCC before the study. The primary outcome was ADR between the two groups. The secondary outcomes were advanced adenoma detection rate (AADR), NPCRN detection rate, sessile serrated lesion detection rate (SSLDR), and withdrawal time between the groups. We used the two-tailed Mann–Whitney U test and Chi-squared statistics for comparison. The ethics committee approved the study, and it was registered with clinicaltrials.gov (NCT04512612)

Results

We recruited 256 patients (PCC-128; WLC-128). The mean age of the entire cohort was 66 + 8.4 years. The mean ADR was comparable between PCC and WLC (70.3% vs. 64.8%, p-0.350). Likewise, the AADR (19.5% vs. 14.8%, p-0.320], and SSLDR (6.25% vs. 1.56%, p-0.102] were similar between the two groups. We found PCC detected more diminutive adenomas (0.97% vs. 0.58%, p-0.025] and NPCRN per colonoscopy (0.35% vs. 0.17%, p-0.028). The mean withdrawal time was longer with PCC compared to WLC (13.3 min vs. 10.2 min, p-0.001). General and advanced endoscopists had no difference in performance measures for APC and NPCRN per colonoscopy.

Conclusion

The ADR in FIT-positive colonoscopy is higher, and both PCC and WLC yielded comparable results. PCC merits consideration because of its increased ability to detect NPCRNs, which are precursors for interval cancer.

Introduction

Thyroidectomy is one of the most common surgical procedures worldwide, yet its potential effects on esophageal function remain inadequately characterized. While post-thyroidectomy issues such as voice changes have been well-documented, alterations in esophageal motility following this procedure have received limited attention in scientific literature.

Aims & Methods

This study aims to evaluate the impact of thyroidectomy on esophageal motility parameters using High-resolution manometry (HRM), with particular attention to upper esophageal sphincter (UES) function. Seventeen patients (11 females), who were to undergo total thyroidectomy or hemithyroidectomy, were prospectively recruited between the months of February and May 2023. Ten of them had goiters, while seven had thyroid nodules. Exclusion criteria were having an age under 30 or over 70 years old, having to also undergo a parathyroid surgery and taking medications that could alter the esophageal sphincter. All of them underwent a pre-operative HRM and a second one thirty days after surgery. HRM were performed according to the Chicago Classification 4.0 and the data were analyzed using the online analysis platform “Swallow Gateway”. Gastrointestinal (GI) symptoms were assessed using a standardized questionnaire, before the first and the second HRM. No after procedural complication was reported.

Results

UES function significatively changed after thyroidectomy, as it is shown by HRM metrics such as Pharyngeal Contractile Integral (CI), Velopharyngeal CI, Hypopharyngeal CI, UES-CI, UES Integrated Relaxation Pressure (UES-IRP), Post-Deglutitive UES CI, Proximal Contractile Integral (PCI), which all significatively decreased (p < 0.05) at the HRM performed after surgery. Compared to Swallow Gateway normal values, there was an important increase of pathological HRM metrics after thyroidectomy. No significant HRM difference was found between the two categories of patients (goiter and thyroid nodules) and no significant correlation was registered between GI symptoms pre- and post-surgery and between GI symptoms and HRM metrics.

Conclusion

Thyroidectomy may significantly affect esophageal motility, especially the function of the upper esophageal sphincter. This finding could be useful in the diagnostic and therapeutic pathway of these patients, although further and larger studies are required to confirm this result.

Introduction

Endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (SESCC) involving the entire circumference carries the extremely high risk of stricture and also raises concerns about curative resection. Therefore, the current Japanese guidelines weakly recommend ESD only for circumferential SESCCs diagnosed as cEP/LPM and sized ≤ 50 mm, while surgery or chemoradiotherapy (CRT) is recommended for circumferential SESCCs other than the above. ¹ However, in clinical practice, ESD is implemented on a case-by-case basis through the discussion in a multi-disciplinary cancer board at each institution because the outcomes of each treatment for circumferential SESCCs remain unclear.²

Aims & Methods

This multicenter prospective observational study aimed to reveal the outcomes of each treatment for circumferential SESCCs. Patients with cT1a-EP/LPM or cT1a-MM/T1b-SM1 N0M0 SESCCs involving the entire circumference were enrolled in this study. At this stage, short-term outcomes, such as the proportion of curative resection after ESD, complete response (CR) after CRT/radiotherapy (RT), and adverse events including esophageal stricture, were evaluated. Curative resection in ESD was defined as pT1a without lymphovascular invasion (LVI). Esophageal stricture was defined as inability to pass the ordinary-sized endoscope thorough the treated site, and refractory stricture was defined as stricture requiring ≥ 6 endoscopic balloon dilation procedures.

Results

A total of 126 patients with circumferential SESCCs were enrolled from 16 Japanese tertiary institutions between May 2021 and November 2024. ESD was performed for 90 (71.4%) patients including 6 undergoing stepwise ESD, surgery for 18 (14.3%), CRT for 16 (12.7%), and RT alone for 2 (1.6%). Median longitudinal length of tumor was 55 (range: 30–140) mm in the ESD group, 80 (50–150) mm in the surgery group, and 70 (30–100) mm in the CRT/RT group. Tumor depth was diagnosed as cEP/LPM in 65.4% (55/84) of the ESD group, 38.9% (7/18) of the surgery group, and 50.0% (9/18) of the CRT/RT group, and the others were diagnosed as cMM/SM1. As stricture prevention method after ESD, local injection or filling of triamcinolone (TA) alone was used in 9 patients (10.7%), and both local injection of TA and oral steroid of prednisolone were used in 75 (89.3%). Among the 63 patients who did not receive additional treatment after ESD, the proportion of stricture and refractory stricture were 46.0% (29/63) and 27.0% (17/63), respectively. Curative resection after ESD was achieved in 58 patients (69.0%), including 46 (83.6%) with cEP/LPM and 12 (41.4%) with cMM/SM1. Of 26 patients with non-curative resection after ESD, 20 (76.9%) received additional treatment of either surgery, CRT, or RT, while the remaining 6 opted for follow-up. Of 18 patients in the surgery group, 7 with cEP/LPM and 4 with cMM/SM1 were diagnosed as pT1aN0 without LVI, while the remaining 7 with cMM/SM1 were diagnosed as pT1b, 3 of whom had lymph node metastasis. Anastomotic stricture was observed in 11.1% (2/18) of patients treated with surgery. Of 18 patients in the CRT/RT group, CR was confirmed in all patients without forming stricture.

Conclusion

Considering the high curative resection rate, ESD could be indicated for circumferential SESCCs diagnosed as cEP/LPM. In contrast, the careful consideration may be required in indicating ESD for circumferential SESCCs diagnosed as cMM/SM1 due to its low curative resection rate. Long-term outcome needs to be confirmed for further treatment comparisons.

References

1. Ishihara R, Arima M, Iizuka T, et al. Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer. Dig Endosc. 2020; 32: 452–93.
2. Kadota T, Ishihara R, Hatta W, et al. Multi-institutional questionnaire on treatment strategies for superficial entire circumferential esophageal squamous cell carcinoma. DEN Open. 2023; 3: e206.

Introduction

Primary biliary cholangitis (PBC) is often associated with extrahepatic autoimmune diseases (EAIDs) such as Sjögren’s syndrome, autoimmune thyroiditis, and connective tissue disorders. While this association suggests a shared immunological predisposition, its effect on disease prognosis remains unclear.

Aims & Methods

This retrospective study included 69 patients diagnosed with PBC, excluding those with overlap syndromes involving autoimmune hepatitis. Patients were divided into two groups: isolated PBC (n = 35) and PBC associated with EAIDs (n = 34). The two groups were compared based on clinical, immunological, elastometric characteristics, disease progression, and prognostic scores (Paris I, Paris II, Rotterdam, Barcelona, Rochester, GLOBE, UK-PBC). Statistical analysis was conducted using appropriate tests, with a significance threshold set at p < 0.05.

Results

The average age at diagnosis was 55.6 years. The disease was initially suspected based on functional symptoms in 39% of cases (fatigue, pruritus, arthralgia), biological cholestasis in 33.3%, and decompensated cirrhosis in 20.3%. The most common associated autoimmune diseases were Sjögren’s syndrome (17.4%), thyroid disorders (13%), and systemic lupus erythematosus (10.1%). All patients received treatment with ursodeoxycholic acid at 13-15 mg/kg/day. No significant differences were found between the two groups regarding functional symptoms, biological markers (bilirubin, albumin, prothrombin time), autoantibodies (AMA, Anti-GP210, anti-SP100, anti-PML), non-invasive fibrosis scores (Fib4, Fibroindex, Fibroscan, S-index), or hepatic complications (HDH, cirrhosis, hepatic encephalopathy, liver-related death). Prognostic scores were also comparable between both groups: Paris I (p = 0.468), Paris II (p = 0.519), GLOBE score (p = 0.6), UK-PBC (p = 0.49), Rotterdam (p = 0.897), Barcelona (p = 0.181), Rochester (p = 0.727).

Conclusion

The presence of extrahepatic autoimmune diseases in PBC does not appear to affect the clinical, biological, or prognostic profiles of patients. Despite their frequency, these comorbidities do not seem to influence the progression of PBC.

Disclosure

None.