Introduction

Pain is the main symptom of acute pancreatitis (AP) and is usually intense. Most patients have relatively rapid pain relief, but some patients may experience more severe and long-lasting pain. Up till now, we cannot predict which patients will do worse. Early prediction of which patients will suffer the most pain would allow decisions to be made about increased analgesic treatment potency or different routes of administration.

Aims & Methods

Our main aim was to evaluate which baseline characteristics in AP are associated with pain evolution the first days of admission. For that purpose, we performed a post-hoc analysis of the international open label randomized clinical trial WATERFALL, which compared aggressive fluid therapy (20 ml/kg bolus followed by 3 ml/kg/h) versus moderate (1.5 ml/kg/h preceded by 10 ml/kg bolus only in case of hypovolemia) based on Lactated Ringer solution. The pain was assessed using the PAN-PROMISE scale (numerical scale with a range of 0 to 10, absence or maximum pain reported by the patient respectively) at baseline, 12, 24, and 48 hours. The predictive effect of 16 baseline variables (at study enrollment) on the evolution of pain was analyzed using a general linear model for repeated measures.

Results

A total of 228 patients were included out of 249 (the ones with PAN-PROMISE at 0,12,24 and 48 h). Younger age, blood leukocyte count, presence of signs or symptoms of dehydration, and active alcohol etiology were predictors of pain in the first 48 hours (p<0,05). With the combination of these variables, we obtained regression lines to predict 0-10 pain in the first 12, 24, and 48 hours. Baseline variables such as sex, smoking, body mass index, comorbidity, hematocrit, creatinine, temperature, heart rate, respiratory rate, biliary etiology, or randomization to aggressive or moderate fluid therapy did not independently predict pain intensity in the first days after AP.

Conclusion

Younger age, blood leukocyte count, presence of signs or symptoms of dehydration, and active alcohol etiology were predictors of pain in the first 48 hours.

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). In ELEVATE UC 52 (NCT03945188), etrasimod was superior to placebo (PBO) in achieving Week (Wk) 52 corticosteroid (CS)-free clinical remission (CR).¹

Aims & Methods

This post hoc analysis reports CS-free efficacy and safety in patients (pts) on baseline (BL) CS. Pts were randomised 2:1 to once-daily etrasimod 2 mg or PBO using a treat-through design (12-wk induction and 40-wk maintenance period). At entry, pts could receive concomitant CS (prednisone [≤ 20 mg/day], budesonide [≤ 9 mg/day] or equivalent) if on a stable dose ≥ 4 wks immediately before screening endoscopy; from Wk 12, CS tapering was recommended. CS-free was defined as withdrawal of CS ≥ 12 wks prior to assessment timepoint. CS-free outcomes assessed were CS-free CR at Wk 52, CS-free endoscopic improvement (EI) at Wk 52, and CR at Wk 12 + CS-free CR at Wk 52. From Wk 12, 4-wk CS‑free symptomatic remission (SR; 4 wk in contrast to ≥ 12-wks CS free) was analysed at each visit. Logistic regressions examined associations with CS-free efficacy at Wk 52. Safety was assessed.

Results

At BL, 32.2% (93/289) and 29.2% (42/144) of etrasimod and PBO pts received CS; of these, significantly more etrasimod vs PBO pts achieved CS-free CR at Wk 52, CS-free EI at Wk 52 and CR at Wk 12 + CS-free CR at Wk 52 (all p<0.05; Table). At Wks 40–52, there were significant differences (16.6–26.6%; p<0.05) in 4-wk CS-free SR between etrasimod and PBO. In this subpopulation, being biologic/Janus kinase inhibitor-naïve was not a significant predictor of 12-wk CS-free CR at Wk 52 (odds ratio [OR]: 3.61; 95% confidence interval [CI] 0.91, 14.39; p=0.07); age, per 10-year increase, was significantly associated (OR: 1.51; 95% CI 1.03, 2.22; p=0.04). Etrasimod vs PBO pts with concomitant CS at BL experienced slightly more adverse events (AEs; not exposure adjusted) (71.0% [66/93] vs 61.9% [26/42]) but fewer serious AEs (6.5% [6/93] vs 14.3% [6/42]), including serious infections (0% [0/93] vs 7.1% [3/42]).

Conclusion

More etrasimod vs PBO pts who received CS at BL met CS‑free efficacy endpoints. Four-wk CS-free SR with etrasimod was superior to PBO from Wk 40. Concomitant CS use at BL had no notable negative effect on the safety of etrasimod, consistent with the overall ELEVATE UC 52 population.¹

References

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

Disclosure

BES: grants/research: Arena, Janssen; speaker: BMS, Janssen, Lilly, Pfizer, Takeda; consultancy/advisory board: 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; stock: Ventyx Biosciences; non-financial support: Janssen, Lilly, Pfizer, Takeda.
YL: speaker: Pfizer Inc, Takeda, Abbvie, Jannsen; Consultancy, Advisory Committee/Board Member: Pfizer Inc, BMS, Takeda, Abbvie, Amgen BioJamp, Lilly.
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.
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.
JP: personal: AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celltrion, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, GSK, Immunic, Janssen, Mirum, Morphic, Nestlé, Origo, Pandion, Pfizer Inc, Progenity, Revolo, Takeda, Theravance Biopharma and Wassermann; grant support: AbbVie, Pfizer Inc.
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 Pharma, Fresenius, Janssen, MSD, Pfizer Inc, Takeda; consultancy/advisory: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Fresenius, Gilead Sciences, IMAB, Janssen, MSD, Mylan, Pfizer Inc, Protagonist, Provention Bio, Takeda, Theravance.

Introduction

There is currently no recommendation regarding preferred drugs for eosinophilic esophagitis (EoE) because their relative efficacy is unclear.

Aims & Methods

We conducted an up-to-date network meta-analysis to compare proton pump inhibitors, off-label and EoE-specific topical steroids, and biologics in EoE. We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to February 2023. We included randomized controlled trials (RCTs) comparing efficacy of all drugs versus each other, or placebo, in adults and adolescents with EoE. Results were reported as pooled relative risks with 95% confidence intervals to summarize effect of each comparison tested, with drugs ranked according to P-score.

Results

We identified 13 RCTscontaining 1327 subjects with EoE. For histological remission defined as ≤15 eosinophils/high-power field (eosinophils/HPF), budesonide orally disintegrating tablet 1mg b.i.d., fluticasone orally disintegrating tablet 1.5mg b.i.d. and 3mg b.i.d., and dupilumab 300mg weekly ranked first, second, third, and fourth, respectively. Results were similar when histological remission was defined as ≤6 eosinophils/HPF. EoE-specific formulations were generally superior to adapted asthma medications in achieving histological remission. For failure to achieve symptom improvement, only budesonide orally disintegrating tablet 1mg b.i.d. and budesonide oral suspension 2mg b.i.d. were significantly more efficacious than placebo. For failure to achieve endoscopic improvement based on the EoE endoscopic reference score, only budesonide orally disintegrating tablet 1mg b.i.d. and budesonide oral suspension 1mg b.i.d. or 2mg b.i.d. were significantly more efficacious than placebo.

Conclusion

Most drugs are effective for achieving histological remission in active EoE, but few are superior to placebo in terms of symptomatic or endoscopic improvement.

Introduction

Climate change is a major challenge to our future generations and environment, and limiting its effects is necessary in every aspect of our daily lives. Endoscopy units are one of the most resource-intensive hospital departments, producing large amounts of contaminated waste, mostly disposed of by incineration, generating large quantities of CO₂. The environmental impact of endoscopy needs to be better investigated as current ESGE/ ESGENA guidelines propose reducing waste by first creating awareness via implementing audits to assess waste production¹. We sought to investigate the feasibility of an audit procedure assessing waste production and mechanisms of disposal to understand where to reduce, reuse or recycle the waste.

Aims & Methods

During one working week in March 2023, we performed a structured waste audit in collaboration with the department for environmental sustainability in the endoscopy department of the university hospital of Basel, a tertiary referral center in northwestern Switzerland, performing >6000 endoscopic procedures per year. Waste was collected separately in patient-specific bags for each procedure, from the preparation of the patient to discharge by two investigators. The use of sharps and reusable equipment (e.g., tubing, etc.) was included in the calculation of the waste generated per procedure.

Results

During the study period,the normal running of the endoscopy unit was not disrupted. Waste produced by 75 examinations was analyzed. Median waste production was 910 g/ Gastroscopy, 1060g/ Colonoscopy, 1110g/ Gastro-and Colonoscopy, 1240 g/ Sigmoidoscopy and 1823 g/ ERCP or EUS. This adds up to 26 kg of waste per day or 52 t of CO₂ generated by incineration per year in our endoscopy unit.

Conclusion

A structured waste audit can easily be incorporated into the daily practice of an endoscopy unit without impacting patient care and using few resources. Creating awareness of waste generation and composition is a crucial first step toward creating sustainable endoscopy practice. The amount of C0₂ generated by our endoscopy unit in a year equals driving eight times around the world. Gastroscopy and colonoscopy should be combined in one procedure when possible.

References

1 Santiago E, Dinis-Ribeiro, Pohl H et al. Endoscopy. 2022; 54

Introduction

Recently, a subcutaneous formulation of biosimilar infliximab (CT-P13) (SC-IFX) has been approved for inflammatory bowel disease (IBD). The aims of this study were to evaluate efficacy, safety, pharmacokinetics and patient experience following a switching to SC-IFX in patients who are in clinical remission on IV-IFX maintenance treatment.

Aims & Methods

Multicentre, descriptive, and observational study including Crohn’s disease (CD) and ulcerative colitis (UC) patients who were going to be changed from IV-IFX to SC-IFX on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD–GETECCU). All patients were on clinical and biological remission at least 24 weeks before changing. Demographic and disease data, clinical activity (Harvey-Bradshaw index for CD and mayo index for UC), analytical data (C reactive protein (CRP) and fecal calprotectin (FC), as well as trough levels were collected at baseline, at 12 and 24 weeks.

Results

One hundred and fifty-five patients were included: 54 UC (35%) and 91 (65%) CD; 44% women and 56% men; age 45.5 years (32-55). IV-IFX was mainly administered due to active disease (72%) and perianal disease (7%) and during 32 months [range 14-56]. Pre-switch, 78 (50.3%) were on 8-weekly dosing of IV-IFX, 77 (49.7%) were with intensification dose and the half (50.3%) were on concomitant immunomodulatory therapy. SC-IFX was mainly switching by COVID-19 pandemic (60%), to increase through levels (15%) or patient request (25%). The majority of patients (140, 90%) remained with standard dose, 8 (5%) required dose intensification (120 mg weekly in 4 and 240 mg every 2 weeks in 4) and 7 (4.5%) had successful de-escalation (120 mg every 3 weeks in 4 and 120 mg every 4 weeks in 3). Clinical indices, CRP levels and FC remained unchanged. Median SC-IFX levels significantly increased from baseline of 4.5 μg/dl [range 2.6-9.2] to 14 μg/dl [range 9.5-16.2] at week 12 and 13.2 μg/dl [range 10.4-19.7] at week 24. No factors (immunossupresor, body mass index, disease location) were associated with the increase of IFX trough levels. During 24 weeks of follow-up, 16 of the 78 patients (20.5%) stopped immunosuppressant treatment. The adverse events were recorded in 9 patients (5.8%), 4 (2.6%) were hospitalized and 4 (2.6%) had surgery (one of them for perianal disease). Nine patients (5.8%) stopped SC-IFX (1 primary failure, 2 loss of response, 4 adverse events, 1 voluntarily, and 1 surgery).

Conclusion

The switch from IV to SC IFX maintains clinical remission safely in IBD patients, offers higher drug levels and a good patient acceptance. However, the significance of higher drug levels with SC-IFX requires further exploration.

Clinical Case Summary

Background: Juvenile polyposis syndrome (JPS) is a rare inherited autosomal dominant disease predisposing to the development of hamartomatous polyps along the gastrointestinal (GI) tract. JPS patients face a significantly higher risk of colorectal cancer (CRC), which makes endoscopic screening mandatory. JPS phenotype in patients with SMAD4 gene mutation, probably due to the dysregulation in the transforming growth factor β (TGF-β)–mediated pathways, is featured by several extraintestinal manifestations, including cutaneous and congenital abnormalities (predominantly, cardiovascular).
Case presentation: Two male brothers, aged 24 and 28 respectively, with a family history of colorectal polyposis and CRC were admitted to our Department in November 2023. For both, the colonoscopy revealed multiple GI polyps, histologically compatible with hamartomatous lesions. Next Generation Sequencing (NGS) analysis was then requested.
In the following 8 weeks, the older brother experienced a cerebral stroke, and a patent foramen ovale (PFO) was detected as the cause of this acute cerebrovascular event determining a permanent neurological impairment. Considering this, a cardiological work-up aiming to assess the same cardiac defect was performed and PFO was finally diagnosed also in the younger brother, as well as a prompt percutaneous PFO closure was disposed for both to prevent further cardiovascular accidents.
Finally, NGS analysis identified a single nucleotide mutation in the locus of the SMAD4 gene (18q21.1) confirming the diagnosis of JPS and the reported events as crucial extra-GI JPS manifestations.
Conclusion: The reported association between SMAD-4 mutation-related JPS and cardiovascular disorders, potentially leading to acute cerebrovascular accidents, highlights the need for an appropriate preventive cardiological workup in young patients for which endoscopy reveals multiple GI tract polyps.

References

[1] Cichy W, Klincewicz B, Plawski A. Juvenile polyposis syndrome. Arch Med Sci. 2014 Jun 29;10(3):570-7. doi: 10.5114/aoms.2014.43750. Epub 2014 Jun 27. PMID: 25097590; PMCID: PMC4107262.
[2] Dal Buono A, Gaiani F, Poliani L, Laghi L. Juvenile polyposis syndrome: An overview. Best Pract Res Clin Gastroenterol. 2022 Jun-Aug;58-59:101799. doi: 10.1016/j.bpg.2022.101799. Epub 2022 Apr 4. PMID: 35988962.
[3] Harris RE, Russell RK. BMPR1A mutation-positive juvenile polyposis syndrome and atrial septal defect: coincidence or association? BMJ Case Rep. 2019 Jun 21;12(6):e229881. doi: 10.1136/bcr-2019-229881. PMID: 31229977; PMCID: PMC6605934.

Clinical Case Summary

Endoscopic full-thickness resection (eFTR) is an emerging technique that enables effective and safe management of complex colorectal (CR) lesions. In recent years, eFTR has been described as an alternative to surgery in selected patients, namely for scars aiming to exclude residual tumors after non-curative endoscopic resection. We present a case of eFTR due to imaging suspicion of intraparietal colorectal recurrence without endoscopic findings.
A 41-year-old woman with Lynch syndrome (dMLH1) and a history of rectal adenocarcinoma underwent anterior resection of the rectum and adjuvant chemoradiotherapy at the age of 20. Afterwards endoscopic surveillance was initiated. At the age of 39, she presented with a suspicious lesion (Paris 0-Is+IIa, NICE 2, JNET2B), 16mm, in the hepatic angle, and underwent enbloc endoscopic mucosal resection. Histopathological analysis revealed a low-grade invasive colorectal carcinoma (CRC) with deep invasion of the submucosa (vertical R1). After a multidisciplinary meeting, complementary surgery was proposed but the patient refused, maintaining close surveillance. Two subsequent endoscopic revisions and two computed tomography (CT) scans showed no signs of macro or microscopic recurrence, even after extensive biopsies of the colonic scar. However, a CT scan 20months post-resection showed a 2cm parietal thickening in the hepatic angle. Suspecting parietal tumor recurrence without superficial endoscopic findings, a transmural endoscopic resection using FTRD® of the scar was performed. Histology revealed no tumor recurrence.
Transmural evaluation of the scar after noncurative endoscopic resection of T1 CRC, whether for excluding residual tumor or during surveillance to exclude recurrence, represents a promising indication for eFTR. This technique has demonstrated to be a safe and effective therapeutic alternative for this new indication, avoiding surgery and its associated morbidity and mortality.

References

Aslanian HR, Sethi A, Bhutani MS, Goodman AJ, Krishnan K, Lichtenstein DR, et al. ASGE guideline for endoscopic full-thickness resection and submucosal tunnel endoscopic resection. VideoGIE 2019;4:343–50. https://doi.org/10.1016/j.vgie.2019.03.010.
Gijsbers K, Laclé M, Elias SG, Backes Y, Bosman J, van Berkel A. Full-Thickness Scar Resection After R1 / Rx Excised T1 Colorectal Cancers as an Alternative to Completion Surgery : Official journal of the American College of Gastroenterology | ACG. Am J Gastroenterol 2022;117:647–53. https://doi.org/10.14309/ajg.0000000000001621.
Pimentel-Nunes P, Libânio D, Bastiaansen BAJ, Bhandari P, Bisschops R, Bourke MJ, et al. Endoscopic submucosal dissection for superficial gastrointestinal lesions: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy 2022;54:591–622. https://doi.org/10.1055/a-1811-7025.