Introduction

According to updated guidelines, non-pedunculated polyps of small size are resected with a cold snare in air dilated intestinal lumen(Conventional Cold Snare Polypectomy-CCSP) [1]. R0 resection rate(R0-RR) using CCSP ranges from 32.9% to 96.6%[2-5] while meta-analyses showed that the incomplete resection rate (IRR) after CCSP was 17.3% [6], highlighting the need for further research regarding the most suitable polypectomy method for small polyps. Recently, several studies have described the benefits of water-aided colonoscopy, as well as safety and efficacy of underwater polypectomy in large colon polyps. However, data on small polyps which are the most commonly diagnosed, are insufficient. In response to this gap in the literature, we conducted the first randomized, double-blind, controlled trial to compare underwater cold snare polypectomy(UCSP) to CCSP for non-pedunculated colon polyps of size 5-10mm.

Aims & Methods

The CCSP procedure involved: opening of the intestinal lumen using air/CO2, snaring of the lesion and surrounding healthy tissue, and excision. On the other, UCSP involved three more steps before snaring of the polyp: complete suction of air, partial opening of the intestinal lumen using sterile water, complete immersion of the lesion in water. In order to determine the IRR, additional biopsies were taken from the horizontal margins of the resection site. All polypectomy–related complications were recorded. The objective of the study was to compare the safety and efficacy between UCSP and CCSP regarding resection of non-pedunculated colon polyps with size 5-10mm. Primary outcome was the investigation of the difference in the rate of area containing muscularis mucosa between the two polypectomy techniques. The secondary outcomes focused on differences in R0-RR, IRR, en-bloc resection, and complications. Patients were allocated with a 1:1 ration to UCSP or CCSP group.If more than one polyp was diagnosed in a patient, then all were resected by the same method. The randomization process was done by using the random numbers method of Microsoft Excel 2016. Both pathologists and patients were blinded.

Results

Between March 2021 and December 2022, a total of 229 patients were enrolled in the study, with 397 polyps(UCSP:198, CCSP:199) included in the per protocol analysis. Results demonstrated that UCSP was superior to CCSP in terms of both muscularis mucosa resection rate (81.72% vs. 72.33%, p=0.003) and IRR (8.5% vs. 3.5%, p=0.05). However, the R0-RR did not differ significantly between the two groups (UCSP: 93.9%, CCSP: 90%, p=0.29). UCSP also achieved a higher rate of en bloc resections than CCSP(98% vs 93.5%, p=0.04). The only complication observed was non-severe intraprocedural bleeding, which was successfully managed during endoscopy(UCSP 0.5%, CCSP 2%, p=0.37). Expert endoscopists in CCSP achieved a higher R0-RR than non-experts (93% vs. 84%, p=0.05), whereas no significant difference in R0 resection rate was observed among different levels of expertise in UCSP. Polyp histology and size were found to affect R0 resection rates in both groups, with serrated histology and sizes of 8-10mm linked to lower R0 resection rates.

Conclusion

UCSP is a safe technique that achieves better results in the resection of muscularis mucosa and is associated with a lower IRR than CCSP, thus reducing the risk of residual or recurrent lesions. Furthermore, the efficacy of UCSP does not depend on the endoscopist's expertise and thus could be the optimal approach for young or inexperienced gastroenterologists.

References

1. Ferlitsch M, Moss A, Hassan C, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy 2017;49:270–97.
2 Maruoka D, Arai M, Akizue N, Ishikawa K, Kasamatsu S, Taida T, Ishigami H, Okimoto K, Saito K, Matsumura T, Nakagawa T, Katsuno T, Kato N. Residual adenoma after cold snare polypectomy for small colorectal adenomas: a prospective clinical study. Endoscopy. 2018 Jul;50(7):693-700. doi: 10.1055/s-0043-124869. Epub 2018 Feb 7. PMID: 29415287. 3
3. Zhang Q, Gao P, Han B, et al. Polypectomy for complete endoscopic resection of small colorectal polyps. GastrointestEndosc 2018;87:733–40
4. Kawamura T, Takeuchi Y, Asai S, et al. A comparison of the resection rate for coldand hot snare polypectomy for 4-9 mm colorectal polyps: a multicentre randomised controlled trial (CRESCENT study). Gut 2018;67:1950–7.
5. Papastergiou V, Paraskeva KD, Fragaki M, et al. Cold versus hot endoscopic mucosal resection for nonpedunculated colorectal polyps sized 6-10 mm: a randomized trial. Endoscopy 2018;50:403–11.
6. Djinbachian R, Iratni R, Durand M, Marques P, von Renteln D. Rates of Incomplete Resection of 1- to 20-mm Colorectal Polyps: A Systematic Review and Meta-Analysis. Gastroenterology. 2020;159(3):904-914.e12. doi:10.1053/j.gastro.2020.05.018

Introduction

Etrasimod is an investigational, once-daily (QD), oral, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator in development to treat immune-mediated inflammatory disorders. CULTIVATE (NCT04173273) is a seamless phase 2/3 trial comprising 5 substudies designed to evaluate the efficacy, safety and tolerability of etrasimod in patients with moderately to severely active Crohn’s disease (CD).

Aims & Methods

Here, we report the induction data from the first substudy (Substudy A). Substudy A was a phase 2, randomised, double-blind study using a 14‑week induction period followed by a 52-week extension period. Adults (18–80 years) with moderately to severely active CD and an inadequate response, loss of response or intolerance to ≥1 conventional or advanced treatments for CD were randomised 1:1 to etrasimod 2 or 3 mg QD. Patients were stratified by baseline biologic failure status and oral corticosteroid use. The primary efficacy endpoint was achievement of endoscopic response (defined as endoscopic remission [SES-CD ≤4 and ≥2-point reduction from baseline with no subscore >1] or ≥50% decrease in SES-CD score) at Week 14. Secondary/exploratory endpoints included achievement of endoscopic remission, clinical remission (CDAI <150) and IBDQ remission (IBDQ ≥170), at Week 14. Outcomes were analysed in the full analysis set (all randomised patients treated with ≥1 dose of etrasimod) using non-responder imputation or observed data.

Results

Of 83 patients randomised to either etrasimod 2 or 3 mg QD, 32/42 (76.2%) and 36/41 (87.8%) completed Week 14, respectively. Overall, 21.4% and 9.8% of patients receiving etrasimod 2 and 3 mg QD, respectively, achieved the primary endpoint of endoscopic response, 14.3% and 7.3% achieved endoscopic remission, 31.0% and 43.9% achieved clinical remission, and 33.3% and 40.0% achieved IBDQ remission at Week 14. Most TEAEs were mild or moderate. The incidence of serious TEAEs (4.8% and 2.4%) and TEAEs leading to discontinuation (4.8% and 7.3%) was low with etrasimod 2 and 3 mg QD, respectively (Table). Two patients randomized to etrasimod 3 mg QD experienced second-degree atrioventricular block type I TEAEs (one patient during 2-mg titration).

Conclusion

Data from this substudy of patients with moderately to severely active CD suggest endoscopic and clinical improvement with both etrasimod 2 and 3 mg QD. However, the small sample size and lack of a placebo arm limit the ability to draw conclusions about efficacy, including comparison between the etrasimod 2 and 3 mg groups. Both doses were well tolerated, and safety was consistent with other etrasimod clinical programmes. Data from the extension phase of Substudy A and the placebo-controlled, dose-ranging phase 2b Substudy 1 are forthcoming.

Disclosure

GD’H: advisor: AbbVie, AstraZeneca, Alimentiv, Bristol-Myers Squibb, Boehringer Ingelheim, Celltrion, Cosmo, Eli Lilly, Galapagos, GSK, Johnson & Johnson, Takeda, Pfizer, Polpharma, Prometheus, Tillotts, Ventyx; speaker: AbbVie, Boehringer Ingelheim, Celltrion, Johnson & Johnson, Takeda, Pfizer, Tillotts.
MCD: grant/research: 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.
LPB: grant/research: Takeda, Fresenius Kabi, Celltrion; consultancy: AbbVie, Alimentiv, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Bristol-Myers Squibb, Celltrion, CONNECT Biopharm, Cytoki, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer, GSK, HAC, IAG Image Analysis, Index, Inotrem, Janssen, Eli Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM, ONO, OSE, Pandion, Par'Immune, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, TiGenix, Tillotts, Viatris, Vifor, Ysopia, Abivax; speaker: Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillotts, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Eli Lilly, Gilead, Viatris, Medac, Sanofi; stock: CTMA.
SD: consultancy/advisory: AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Gilead, Hospira, Janssen, Johnson & Johnson, MSD, Mundipharma, Pfizer, Roche, Sandoz, Takeda, TiGenix, UCB, Vifor; speaker: AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, Takeda; directorship/ownership interests: Gastroenterology and Endoscopy.
BES: grant/research: Arena, Janssen. Lecture fees/Speakers Bureau: BMS, Janssen, Lilly, Pfizer, Takeda; consultancy/advisory: 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.
DCW: grant/research: AbbVie, Arena, Bristol Myers Squibb, Janssen, Pfizer, Takeda, Ventyx; speaker: AbbVie, Bristol Myers, Squibb, Janssen, Pfizer, Takeda; consultancy: AbbVie, Arena, Bristol Myers Squibb, Janssen, Pfizer, Takeda.
AJY: consultancy: Pfizer, Arena, Takeda, Bristol-Myers Squibb; speaker: Bristol-Myers Squibb.
MVC: grant support: Pfizer, Janssen, Novartis, Bristol-Myers Squibb; consultancy fees: AbbVie, Arena, Bristol-Myers Squibb, Medtronic, Pfizer, Prometheus, Eli Lilly, Janssen, Takeda; speaker fees: AbbVie, Janssen, Medtronic, Pfizer, Bristol-Myers Squibb, Takeda.
DD: employee of Pfizer Inc at the time of the abstract.
IM, HT, GG, CS: employees & shareholders of Pfizer Inc.
CL, FC: employees of Pfizer Inc at the time of this analysis.
JZ: employee & shareholder of Arena Pharmaceuticals.
AMcD: employee & shareholder of Pfizer Ltd.
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, Protagonist, Provention, Takeda, Theravance.
BGF: consultant/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, 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.
SV: grant/research: 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; speaker: AbbVie, Dr. Falk, Ferring, Hospira, MSD, Takeda, Tillotts.

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

Eosinophilic esophagitis (EoE) is a chronic type 2 inflammatory disease with increasing incidence and prevalence. Patients with EoE usually present with symptoms of dysphagia that impact their quality of life. In the 3-part, Phase 3 LIBERTY EoE TREET study (NCT03633617), dupilumab improved histologic, symptomatic, and endoscopic aspects of EoE up to 52 weeks.

Aims & Methods

The aim of this analysis was to assess the effect of dupilumab on symptoms of dysphagia in the 28-week extended treatment period of LIBERTY EoE TREET in patients who switched from placebo to dupilumab at 24 weeks. In Parts A and B, patients received dupilumab 300 mg or placebo weekly (qw) for 24 weeks. Patients who completed Parts A and B entered Part C - a 28-week extended treatment period in which all patients received dupilumab 300 mg qw; patients entering Part C remained blinded to their treatment in Parts A and B. Dysphagia Symptom Questionnaire (DSQ) score and number of days with dysphagia (assessed using the DSQ) were calculated over a 14-day period. Percent change in DSQ score and in number of days with dysphagia from Week 24 through Week 52 vs the Week 24 baseline were assessed for patients who switched from placebo to dupilumab 300 mg qw at Week 24 and or continued on dupilumab 300 mg.

Results

Mean (SD) DSQ score after 24 weeks of placebo was 24.7 (19.6) and 21.5 (18.4) in Parts A (n=37) and B (n=37), respectively. Significant improvements in DSQ score were observed within 4 weeks of the switch to dupilumab 300 mg qw (mean percent reduction: 31.5% and 29.9%). After 28 weeks (at Week 52), mean percent reduction in DSQ score was 63.6% and 59.7%. After 24 weeks of placebo, mean (SD) days with dysphagia was 6.6 (4.7) and 6.0 (4.7) in Parts A and B, respectively. At Week 52, there was a 63.2% and 46.8% mean reduction in the number of days with dysphagia.

Conclusion

In patients who initially received 24 weeks of placebo, weekly treatment with dupilumab 300 mg resulted in rapid (within 4 weeks) and sustained (up to 28 weeks) improvement in symptoms of dysphagia as assessed by the DSQ score. The magnitude of the improvement in dysphagia observed after switching from placebo to dupilumab was similar to that seen at 4 weeks in patients who originally initiated dupilumab in Parts A and B of the study.

Disclosure

Dellon ES. Abbott, Abbvie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Dr. Falk Pharma, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio – consultant. Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Shire/Takeda – research funding. Allakos, Aqilion, Holoclara, Invea – educational grants.
Chehade M. Adare Pharma Solutions/Ellodi, Allakos, AstraZeneca, BMS, Nexstone Immunology, Phathom, Recludix Pharma, Regeneron Pharmaceuticals Inc., Sanofi, and Shire/Takeda ‒ consultant. Adare Pharma Solutions/Ellodi, Allakos, AstraZeneca, Celgene/BMS, Danone, Regeneron Pharmaceuticals Inc., and Shire/Takeda ‒ research funding.
Bredenoord AJ. Alimentiv, Aqilion, AstraZeneca, Dr. Falk Pharma, Eupraxia, Laborie, Medtronic, Reckitt, Regeneron Pharmaceuticals Inc., and Sanofi ‒ consultant. Dr Falk Pharma, Norgine, Nutricia, Sanofi, SST, Regeneron Pharmaceuticals Inc., and Thelial ‒ research funding. Alimentiv, Aqilion, AstraZeneca, Dr Falk Pharma, Eupraxia, Laborie, Medtronic, Reckitt, Regeneron Pharmaceuticals Inc., and Sanofi ‒ speaker fees.
Spergel JM. Allakos, DBV Technologies, Novartis, Regeneron Pharmaceuticals Inc., and Shire/Takeda – consultant. DBV Technologies and Regeneron Pharmaceuticals Inc. ‒ research grant support.
Xia C, McCann E, Khodzhayev A, Radwan A. Regeneron Pharmaceuticals Inc. – employees and shareholders.
Tilton ST, Pela T, Jacob-Nara JA. Sanofi – employee, may hold stock and/or stock options in the company.

Introduction

Deficiency of serum 25-hydroxyvitamin D [25(OH)D] was associated with decreased short-term response to anti-tumor necrosis factor-alpha (TNFα) agents in adults with inflammatory bowel disease (IBD). Data on the long-term outcome of pediatric IBD with 25(OH)D deficiency under anti-TNFα therapy are scarce. The aim of this study was to evaluate the relation between serum 25(OH)D levels and the long-term outcome of pediatric IBD under anti-TNFα therapy.

Aims & Methods

Children (<18 years) with IBD that were treated with anti-TNFα agents, and had 25(OH)D levels measured at the initiation of therapy and at least 12 months of follow up under this therapy were included. Demographic, clinical and laboratory data were retrospectively collected. IBD activity was measured by Pediatric Crohn's Disease Activity Index (PCDAI) or Pediatric ulcerative colitis activity index (PUCAI). IBD outcomes were defined as clinical response (reduction of PCDAI > 12.5 or PUCAI > 20 points), clinical remission (PCDAI or PUCAI < 10 points), laboratory remission (C-reactive protein < 5 mg/L and fecal calprotectin < 150 mcg/g), IBD exacerbation (relapse of clinical symptoms accompanied with an elevation above 10 points in the PCDAI or the PUCAI), IBD-related hospitalization, surgery and durability of therapy. Vitamin D deficiency was defined as serum 25(OH)D levels < 30 ng/ml.

Results

Of 530 children with IBD, 150 were treated with anti-TNFα agents and 84 [58 Crohn's disease, 26 ulcerative colitis, median age 15.2 (12.8-16.5) years] met the inclusion criteria. Their median 25(OH)D level was 23 (16.3-29.6) ng/ml, and 65 (77.4%) were 25(OH)D-deficient. 25(OH)D levels above 30 ng/ml were significantly associated with clinical response [HR=4 (1.43-11.11), P=0.008], clinical remission [HR=4.62 (2.56-8.33), P<0.001] and laboratory remission [HR=6.34 (3.39-11.84), P<0.001). Disease exacerbation, IBD-related hospitalization and surgery were non-significantly more prevalent among 25(OH)D-deficient children (12.2% vs. 5.3%, 13.8% vs. 0, 3.1% vs. 0, respectively, P=NS). While anti-TNFα trough levels were similar between 25(OH)D-deficient and non-deficient children, intensification of anti-TNFα therapy was more prevalent among 25(OH)D-deficient children (64.6% vs. 21.1%, P<0.001), as was discontinuation of anti-TNFα therapy (32.3% vs. 10.5%, P=0.061). In a multivariate analysis that included age, sex, IBD type, disease duration and anti-TNFα trough levels, 25(OH)D levels above 30 ng/ml were significantly associated with clinical response and remission [HR=3.92 (1.52-10.08), P=0.005 and HR=5.23 (1.88-14.55), P=0.002, respectively].

Conclusion

Deficiency of serum 25(OH)D is an independent predictor to poor IBD outcome under anti-TNFα therapy in children with IBD. Prospective studies are needed to determine whether supplementation of vitamin D can improve IBD outcome under anti-TNFα therapy.

Introduction

The Epi-IBD cohort is a prospective European population-based cohort of 1,390 patients diagnosed with inflammatory bowel disease (IBD) in 2010 and 2011 according to Copenhagen criteria. Of these, 482 were diagnosed with Crohn’s Disease (CD), 817 with ulcerative colitis (UC) and 91 with IBD unclassified (IBDU). The Epi-IBD cohort was established to examine differences in incidence, treatment strategies, disease course and prognosis among IBD patients in Eastern and Western Europe.

Aims & Methods

This study aims to describe the use of biological therapy as well as the treatment prior to biological therapy. IBD patients were followed prospectively from the time of diagnosis until the 31^st December 2020, death, emigration or loss of follow-up. Clinical data on surgery, hospitalizations, and medical treatment, were captured throughout the follow-up period and entered into a validated web-database, www.epi-ibd.org.

Results

During a median follow-up period of 10.7 (interquartile range (IQR), 10.0-11.4) years, 34% (N=165/482) of CD and 15% (N=122/817) of UC patients were started on biological therapy. Biological therapy was initiated within the first year after diagnosis in 16.8% (N=81/482) of all CD and 3.8% (N=31/817) of all UC patients. In median biological therapy was started at 1.0 year (IQR, 0.3-3.1) and 2.7 years (IQR, 1.6-4.0) after CD and UC diagnosis, respectively. First-line biological therapy was infliximab in 74% (N=213/287) and adalimumab in 22% (N=64/287) of the patients. The remaing (N=10/287) received either Golimumab, Vedolizumab, Ustekinumab or were part of a trial/unknown. The sequences of biological therapies are displayed in Sankey diagrams, Figures 1 and 2. Herein illustrated is that 34% (N=56/165) CD and 34% (N=41/122) UC received at least two different biological drugs. Immunomodulators were initiated simultaneously to the first biological therapy in 19% (N=31/165) of CD patients and in 9% (N=11/122) of UC patients. Overall 63% (N=104/165) CD and 51% (N=62/122) UC patients were receiving concomittant immunomodulators with the first biological therapy.
The sequences of therapy leading up to biological therapy are displayed in Sankey diagrams, Figures 3 and 4. Herein illustrated is that the most common sequence of treatment before the first biological therapy for CD was 1) Steroids, 2) Immunomodulators (21%, N=34/165), and for UC was 1) 5-aminosalicylic-acid (5ASA), 2) Steroids, 3) Immunomodulators (39%, N=48/122). Prior to the first biological therapy one, two and three or more courses of systemic steroid were used in 41%, 28% and 17% (N=67, 47 and 28) of CD patients and 43%, 24% and 26% (N=52, 29 and 32) of UC patients. In 14% (N=23/165) and 7% (N=9/122) of CD and UC patients, systemic steroids were not used prior to first biological therapy. In patients having immunomodulators prior to biological therapy, these were administered for a median of 0.5 (IQR, 0.1-1.9) years and 1.1 (IQR, 0.2-3,2) years in CD and UC, respectively. For 5ASA this was 0.8 (IQR, 0.2-1.5) years for CD and 2.2 (IQR, 0.8-4.3) years for UC.

Conclusion

In this multicenter European population-based cohort, different prescribing patterns for biologics emerge: 34% of CD and 15% of UC patients received biologics within 10 years after diagnosis. Infliximab was the most common first-line biological therapy. Only about half of the patients received concomitant immunomodulators. Prior to the first biological therapy, most patients were exposed to systemic steroids and many to repeated courses.

Introduction

Most clinical trials of systemic ulcerative colitis (UC) therapies exclude patients (pts) with isolated proctitis, who are considered a more treatment-refractory population, creating a need for clinical evidence. 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. The phase 3 etrasimod ELEVATE UC trials included pts with isolated proctitis (< 10 cm rectal involvement), provided they met all other eligibility criteria.¹

Aims & Methods

This post hoc analysis assessed predefined efficacy and safety outcomes in subgroups of pts with isolated proctitis and more extensive colitis (proctosigmoiditis/left-sided colitis/pancolitis). In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), pts (aged 16–80 years) with moderately to severely active UC were randomised 2:1 to etrasimod 2 mg once daily or placebo. ELEVATE UC 52 comprised a 12-week (wk) induction period followed by a 40-wk maintenance period with a treat-through design. ELEVATE UC 12 comprised a 12-wk induction period. Clinical endpoints were assessed in pts with isolated proctitis (data pooled from both trials) and in pts with more extensive colitis (individual trial data). Sustained and corticosteroid-free clinical remission were assessed at Wk 52 (ELEVATE UC 52 only). Bowel urgency Numeric Rating Scale (NRS) was assessed at Wks 12 and 52. Safety was assessed up to Wk 52.

Results

This analysis included 64 (pooled; Wk 12) and 36 (ELEVATE UC 52; Wk 52) pts with isolated proctitis, and 397 (ELEVATE UC 52; Wks 12 and 52) and 326 (ELEVATE UC 12; Wk 12) pts with more extensive colitis. Similar proportions of pts with isolated proctitis achieved the predefined efficacy endpoints vs those with more extensive colitis (Table). Pts with isolated proctitis receiving etrasimod had similar improvements in urgency NRS scores vs those with more extensive colitis (mean change from baseline: Wk 12, -2.8 vs -2.9 [both trials]; Wk 52, -5.0 vs -4.1). Safety in pts with isolated proctitis was generally similar to that in the overall trial population.¹

Conclusion

Etrasimod treatment had similar efficacy in pts with isolated proctitis and in those with more extensive colitis. Prospective confirmation in larger pt cohorts with isolated proctitis is necessary. Safety was consistent with the overall population.¹

References

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

Disclosure

LPB: research: Takeda, Fresenius Kabi, Celltrion; consultancy: AbbVie, Alimentiv, Alma, Amgen, Applied MolecularTransport, Arena, Biogen, BMS, Celltrion, CONNECTBiopharm, Cytoki, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer, GSK, HAC, IAG ImageAnalysis, Index, Inotrem, Janssen, Eli Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM, ONO, OSE, Pandion, Par'Immune, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, TiGenix, Tillotts, Viatris, Vifor, Ysopia, Abivax; speaker: Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillotts, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Eli Lilly, Gilead, Viatris, Medac, Sanofi; stock: CTMA.
MCD: research: Janssen; consultancy: AbbVie, Arena, BMS, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, Janssen, Pfizer, Prometheus, Takeda, Trellus Health, UCB; shares/royalties: Trellus; directorship/ownership interests: Trellus.
BES: research/grants: Arena, Janssen. Lecture/Speakers Bureau: BMS, Janssen, Lilly, Pfizer, Takeda. Consultancy: 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.
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, Wassermann; grants: AbbVie, Pfizer.
SS: speaker: AbbVie, Arena, Biogen, BMS, Celgene, Celltrion, Dr. Falk, Fresenius, Janssen, MSD, Pfizer, Takeda; consultancy/advisory: AbbVie, Arena, Biogen, BMS, Celgene, Celltrion, Dr. Falk, Fresenius, Gilead, IMAB, Janssen, MSD, Mylan, Pfizer, Protagonist, Provention, Takeda, Theravance.
WR: speaker: AbbVie, Celltrion, Dr. Falk, Ferring, Janssen, Galapagos, MSD, Roche, Pfizer, Pharmacosmos, Shire, Takeda, Therakos; consultant: AbbVie, Amgen, AOP Orphan, Arena, Astellas, AstraZeneca, Bioclinica, Boehringer Ingelheim, BMS, Calyx, Celgene, Celltrion, Eli Lilly, Dr. Falk, Ferring, Galapagos, Gatehouse, Genentech, Gilead, Grünenthal, ICON, Index, Inova, Janssen, Landos Biopharma, Medahead, MedImmune, Microbiotica, Mitsubishi Tanabe, MSD, Novartis, OMass, Otsuka, Parexel, Periconsulting, Pharmacosmos, Pfizer, Protagonist, Provention, Quell, Sandoz, Seres, Setpointmedical, Sigmoid, Sublimity, Takeda, Teva, Therakos, Theravance, Zealand; advisory board: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Celltrion, Galapagos, Janssen, Mitsubishi Tanabe, MSD, Pharmacosmos, Pfizer, Sandoz, Takeda; research: AbbVie, Janssen, MSD, Sandoz, Sanofi, Takeda.
BGF: consultant/advisory: AbbVie, AbolerIS, AgomAB, AllianThera, Amgen, AnaptysBio, Applied Molecular Transport, Arena, Avoro Capital, Atomwise, BIOJAMP, Biora, Boehringer Ingelheim, Boxer, Celsius, BMS, 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, 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.
SD: consultancy/advisory: AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Gilead, Hospira, Janssen, J&J, MSD, Mundipharma, Pfizer, Roche, Sandoz, Takeda, TiGenix, UCB Vifor; speaker: AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, Takeda; directorship/ownership interests: Gastroenterology and Endoscopy.
AJY: consultancy: Pfizer, Arena, Takeda, BMS; speaker: BMS.
GD’H: advisor: AbbVie, AstraZeneca, Alimentiv, BMS, Boehringer Ingelheim, Celltrion, Cosmo, Eli Lilly, Galapagos, GSK, J&J, Takeda, Pfizer, Polpharma, Prometheus, Tillotts, Ventyx; speaker: AbbVie, Boehringer Ingelheim, Celltrion, J&J, Takeda, Pfizer, Tillotts.
MG, KW, JCW, IM, AMcD, LB, CJR: Pfizer employees & shareholders.
SV: research: AbbVie, MSD, Pfizer, Galapagos, Takeda; consultancy: AbbVie, AbolerIS, Alimentiv, Arena, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Dr. Falk, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, J&J, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillotts, Zealand; speaker: AbbVie, Dr. Falk, Ferring, Hospira, MSD, Takeda, Tillotts.