Abstracts

LB01 Etrolizumab versus infliximab for treating patients 35RASpberry809 with moderately to severely active ulcerative colitis: Results from the Phase III GARDENIA study

S Danese¹, J-F Colombel², M Lukas³, JP Gisbert⁴, G D’Haens⁵, B Hayee⁶, R Pannacione⁷, H-S Kim⁸, W Reinisch⁹, H Tyrrell¹⁰, YS Oh¹¹, S Tole¹¹, A Chai¹¹, K Chamberlain-James¹⁰, MT Tang¹¹, S Schreiber¹², the GARDENIA Study Group; Drs. Danese and Colombel contributed equally to this work

¹Humanitas University, Milan, Italy

²Icahn School of Medicine at Mount Sinai, New York, USA

³Charles University, Prague, Czech Republic

⁴La Princesa University Hospital, IIS-IP and CIBEREHED, Madrid, Spain

⁵Amsterdam University Medical Center, Amsterdam, The Netherlands

⁶Kings College London, London, UK

⁷University of Calgary, Calgary, Canada

⁸Yonsei University, Wonju College of Medicine, Internal Medicine, Wonju, Republic of Korea

⁹Medical University of Vienna, Vienna, Austria

¹⁰Roche Products Limited, Welwyn Garden City, UK

¹¹Genentech, Inc., South San Francisco, USA

¹²Christian-Albrechts University, Kiel, Germany

Contact e-mail address: silvio.danese@hunimed.eu

Introduction

Etrolizumab, an anti-β7 monoclonal antibody, binds α4β7 and αEβ7 integrins to inhibit both trafficking of immune cells into the gut and their inflammatory effects on the gut lining. In this head-to-head study, we aimed to demonstrate the superiority of etrolizumab over infliximab in patients with ulcerative colitis (UC) naive to anti-tumor necrosis factor agents (anti-TNFs).

Aims and methods: GARDENIA (NCT02136069), a Phase III randomized, double-blind, double-dummy study, enrolled adult patients with moderately to severely active UC (defined as Mayo Clinic total score (MCS) of 6–12 with an endoscopy subscore of ≥2, a rectal bleeding subscore (RBS) of ≥1, and a stool frequency subscore ≥1) naive to anti-TNFs. Patients were randomized 1:1 to receive either subcutaneous etrolizumab 105 mg every four weeks or intravenous infliximab 5 mg/kg at weeks 0, 2, and 6, and then every eight weeks through week 54. The primary endpoint of this study was clinical response at week 10 (defined as decrease in MCS of ≥3 and 30% reduction from baseline and ≥1-point decrease in RBS or absolute RBS of 0 or 1) and clinical remission at week 54 (defined as MCS ≤2, with individual subscores ≤1).

Results

A total of 397 patients were randomized and treated (etrolizumab, 199; infliximab, 198). In the etrolizumab and infliximab arms, respectively, 189 (95.0%) and 182 (91.9%) patients completed the study through week 10, and 95 (47.7%) and 103 (52.0%) patients completed the study through week 54. Baseline demographics and disease characteristics were balanced across treatment arms. Median patient age was 37 years, median duration of disease was 3.82 years, and median MCS at baseline was 9. At baseline, 29% of patients were taking corticosteroids (CS), 19% were taking immunosuppressants (IS), and 14% were taking both CS and IS. GARDENIA did not meet its primary endpoint; 37/199 (18.6%) patients treated with etrolizumab and 39/198 (19.7%) patients treated with infliximab achieved both clinical response at week 10 and clinical remission at week 54 (p = 0.8114). At week 54, endoscopic remission was achieved in 17.6% and 22.7% of etrolizumab- and infliximab-treated patients, respectively. Endoscopic improvement at week 54 was achieved in 27.1% and 32.3% of patients, and clinical remission at week 54 was achieved in 20.1% and 23.7% of etrolizumab- and infliximab-treated patients, respectively. Among patients with clinical response at week 10, 39/117 (33.3%) etrolizumab-treated patients and 37/98 (37.8%) infliximab-treated patients achieved clinical remission at week 54. Results of additional secondary endpoints can be found in the Table. Adverse events (AEs) were generally comparable between study arms. Most AEs were nonserious and grade 1 or 2. There were no deaths related to study drug or cases of progressive multifocal leukoencephalopathy during the study.

Abstract No: LB01.

Key Secondary Endpoints

	Etrolizumab (N=199)	Infliximab (N=198)	Treatment difference (95% CI)	p-Valuea
Endoscopic remissionb at week 54	35 (17.6%)	45 (22.7%)	–5.0% (–12.8, 2.9)	0.2168
Endoscopic improvementc at week 54	54 (27.1%)	64 (32.3%)	–4.9% (–13.8, 4.1)	0.2845
Clinical remission at week 54	40 (20.1%)	47 (23.7%)	–3.4% (–11.5, 4.7)	0.4056
Clinical remission at week 10	41 (20.6%)	65 (32.8%)	–12.0% (–20.5, –3.3)	0.1293
CS-free clinical remissiond at week 54	13/84 (15.5%)	15/86 (17.4%)	–0.8% (–12.0, 10.7)	0.8941
Clinical remission at week 54 among clinical responders at week 10	37/98 (37.8%)	39/117 (33.3%)	5.3% (–7.5, 18.1)	0.4196
Clinical remission at weeks 10 and 54	21 (10.6%)	26 (13.1%)	–2.4% (–8.9, 4.1)	0.4591

^aSince the primary endpoint was not met, no key secondary endpoints were formally tested. Nominal p-values are shown here.

^bMayo Clinic endoscopic subscore=0.

^cMayo Clinic endoscopic subscore ≤1.

^dClinical remission with no CS use for 24 weeks prior to week 54 in patient using CS at baseline.

CI: confidence interval; CS: corticosteroid.

Conclusion

Although etrolizumab did not meet statistical criteria for superiority at week 54, rates of clinical and endoscopic outcomes at week 54 were generally numerically similar between etrolizumab and infliximab. Etrolizumab treatment was well tolerated.

Disclosure: SD reports other from Abbvie, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ely Lilly, Enthera, Ferring Pharmaceuticals, Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB, Inc., Vifor. JC reports research grants from AbbVie, Janssen Pharmaceuticals, Takeda; payment for lectures from AbbVie, Amgen, Allergan, Inc., Ferring Pharmaceuticals, Shire, Takeda; consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene Corporation, Celltrion, Eli Lilly, Enterome, Ferring Pharmaceuticals, Geneva, Genentech, Janssen Pharmaceuticals, Immunic, Landos, Ipsen, Medimmune, Merck, Novartis, O Mass, Otsuka, Pfizer, Shire, Takeda, Tigenix, Viela bio; and stock options in Intestinal Biotech Development and Genfit. ML and BH have nothing to disclose. JP-G has served as a speaker, a consultant, and advisory member for or has received research funding from MSD, Abbvie, Hospira, Pfizer, Kern Pharma, Biogen, Takeda, Janssen, Roche, Sandoz, Celgene, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Vifor Pharma. GD’H reports personal fees from Abbvie, Arena Pharmaceuticals, BMS, Celltrion, Galapagos, Roche/Genetech, Gilead, GossamerBio, Immunic, Kintai, Mitsubishi Pharma, Nextbiotics, Prodigest, Procise Diagnostics, Protagonist, Redhill, Tillotts; grants and personal fees from Boehringer Ingelheim, Eli Lilly, GSK, Pfizer, Johnson & Johnson, Takeda, Prometheus Laboratories, Progenity, Robarts Clinical Trials; and grants from Medtronic. RP reports consultant fees for AI4GI, AbbVie, Arena Pharmaceuticals Amgen, Atlantic Healthcare, BioBalance, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Cosmo Technologies, Coronado Biosciences, Eagle, Eisai Medical Research, Elan, EnGene, Eli Lilly, Ferring, Genentech, Sanofi Genzyme, Gilead, Given Imaging, GlaxoSmithKline, Janssen, Lycera, Meda, Merck & Co., Inc., Merck Research Laboratories, Merck Serono, Novo Nordisk, PDL Biopharma, Pfizer, Robarts Clinical Trials, Prometheus Laboratories, Protagonist, Receptos, Salix, Sandoz, Shire Pharmaceuticals, Sigmoid Pharma, Sublimity, Takeda, Theravance; speaker fees for Abbvie, AstraZeneca, Celgene, Ferring, Janssen, Merck, Pfizer, Prometheus, Sandoz, Shire, Takeda; advisory Board fees for Abbvie, Abbott, Amgen, Aptalis, AstraZeneca, Baxter, Biogen Idec, Eisai, Ferring, Genentech, Janssen, Merck, Shire, Elan, GlaxoSmithKline, Hospira, Pfizer, Bristol-Myers Squibb, Takeda, Cubist, Celgene, Salix; research/educational support from Abbvie, Ferring, Janssen, Shire, Takeda. HK reports investigator fees from Genentech, Takeda, Lilly, GSK, Theravance, BMS, Allergan (one of PIs on ongoing clinical trials). WR reports speaker fees for Abbvie, Celltrion, Falk Pharma GmbH, Janssen, Mitsubishi Tanabe Pharma Corporation, Pfizer, Shire, Takeda; consultant fees for AbbVie, Algernon, Amgen, AM Pharma, AMT, AOP Orphan, Arena Pharmaceuticals, Astellas, Roland Berger GmBH, Bioclinica, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Covance, Eli Lilly, Falk Pharma GmbH, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Intrinsic Imaging, Janssen, Johnson & Johnson, LivaNova, Mallinckrodt, Mitsubishi Tanabe Pharma Corporation, MSD, Nash Pharmaceuticals, OMass, Parexel, Periconsulting, Pharmacosmos, Prometheus, Protagonist, Provention, Roche, Robarts Clinical Trial, Sandoz, Seres Therapeutics, Setpointmedical, Sigmoid, Sublimity, Takeda, Therakos, Theravance, Tigenix, Zealand; fees as an advisory board member for Abbvie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Mitsubishi Tanabe Pharma Corporation, MSD, Pharmacosmos, Pfizer, Prometheus, Sandoz, Takeda, Therakos, Tigenix, Zealand. HT and YO are Roche employees and stockholders. ST is a Genentech employee and Roche stockholder. AC is an employee of Genentech, a member of the Roche Group, and owns Roche stocks as an employee. KC-J reports other from Roche Genussscheine (non-voting shares). MT reports personal fees from Roche/Genentech. SS reports personal fees from Abbvie, Arena, BMS, Biogen, Celltrion, Celgene, IMAB, Gilead, MSD, Mylan, Pfizer, Fresenius, Janssen, Takeda, Theravance, provention Bio, Protagonist, Falk.

LB02 Ozanimod as induction therapy in moderate-to-severe ulcerative colitis: Results from the Phase III, randomized, double-blind, placebo-controlled True North study

W Sandborn¹, GR D’Haens², DC Wolf³, SB Hanauer⁴, I Jovanovic⁵, S Ghosh⁶, A Petersen⁷, SY Hua⁷, JH Lee⁷, L Charles⁷, K Usiskin⁷, S Danese⁸, BG Feagan⁹

¹University of California San Diego, Division of Gastroenterology, San Diego, USA

²Amsterdam University Medical Center, Inflammatory Bowel Disease Center, Amsterdam, The Netherlands

³Atlanta Gastroenterology Associates, Atlanta, USA

⁴Feinberg School of Medicine, Chicago, USA

⁵University Hospital Medical Centre Bezanijska Kosa, Division of Gastroenterology, Belgrade, Serbia

⁶University of Calgary, Alberta, Canada

⁷Bristol-Myers Squibb Company, Princeton, USA

⁸Humanitas Clinical and Research Center, Inflammatory Bowel Diseases Center, Milan, Italy

⁹Western University, London, Canada

Contact e-mail address: wsandborn@ucsd.edu

Introduction

Ozanimod is an orally administered sphingosine-1-phosphate (S1P) receptor modulator that selectively targets S1P₁ and S1P₅. Ozanimod demonstrated efficacy and safety for up to 32 weeks of treatment in patients with moderate-to-severe ulcerative colitis (UC) in the randomized, Phase II TOUCHSTONE study.¹ Here, we report 10-week induction period findings from a Phase III, randomized, double-blind study in patients with moderate-to-severe UC (True North; NCT02435992). Results from the maintenance period are reported separately (Danese et al., abstract LB10).

Aims and methods: Eligible adults with moderate-to-severe UC (total Mayo score 6–12 with a Mayo endoscopy score ≥2 on oral aminosalicylates or corticosteroids were randomized 2:1 to receive ozanimod HCl 1 mg (equivalent to ozanimod 0.92 mg) or placebo once daily (stratified by prior tumor necrosis factor inhibitor (TNFi) and corticosteroid use at screening) during a 10-week induction period. The primary endpoint was the proportion of patients in clinical remission per the three-component Mayo score at week 10. Ranked secondary endpoints were proportions of patients with a clinical response, endoscopic improvement, and mucosal healing, as defined in the Table. A closed hierarchical procedure was used for hypothesis testing.

Results

A total of 645 patients were randomized to receive ozanimod (n = 429) or placebo (n = 216), of whom 94% and 89%, respectively, completed the induction period. At study entry, mean age was 42 years, 60% were male, and mean disease duration was seven years; patient characteristics were well-balanced across treatment groups. All primary and key secondary efficacy endpoints showed statistically significant improvements with ozanimod vs. placebo at week 10 (Table). For the primary endpoint, 18.4% and 6.0% of patients in the ozanimod and placebo groups, respectively, achieved clinical remission at week 10 (absolute difference 12.4%; 95% CI 7.5–17.2; p < 0.0001). Key secondary endpoints of clinical response (p < 0.0001), endoscopic improvement (p < 0.0001), and mucosal healing (p < 0.001) were also statistically significant for ozanimod vs. placebo. In patients with prior TNFi exposure, clinical remission results favored ozanimod over placebo, but this was not significant, while a nominally statistically significant difference was observed for clinical response. The most common treatment-emergent adverse events (TEAEs) for patients who received ozanimod vs. placebo, respectively, were anemia (4.2% vs. 5.6%), nasopharyngitis (3.5% vs. 1.4%), and headache (3.3% vs. 1.9%). Cardiovascular events were infrequent and included bradycardia (0.5% vs. 0%) and hypertension (1.4% vs. 0%). Frequencies of serious TEAEs were 4.0% vs. 3.2%, respectively, and serious infections occurred in <1% in each group.

Conclusion

Ozanimod treatment for 10 weeks in patients with moderate-to-severe UC led to statistically significant improvements in clinical remission, clinical response, endoscopic improvement, and mucosal healing. Safety findings were consistent with ozanimod’s known profile and a moderate-to-severe UC study population; no new safety signals were observed with ozanimod in this study.

Abstract No: LB02.

Efficacy Results at Week 10

Endpoint	Ozanimod HCl 1 mg, n (%) (N = 429)	Placebo, n (%) (N = 216)	Percent difference (95% CI)	Odds ratio (95% CI)	p-Value
Clinical remissiona	79 (18.4)	13 (6.0)	12.4 (7.5, 17.2)	3.59 (1.94, 6.64)	<0.0001
Prior TNFi therapy	n = 130 13 (10.0)	n = 65 3 (4.6)	5.4 (–1.8, 12.6)	2.32 (0.63, 8.49)	0.195
Clinical responseb	205 (47.8)	56 (25.9)	21.9 (14.4, 29.3)	2.67 (1.86, 3.84)	<0.0001
Prior TNFi therapy	n = 130 48 (36.9)	n = 65 12 (18.5)	18.5 (6.0, 31.0)	2.62 (1.27, 5.41)	0.008
Endoscopic improvementc	117 (27.3)	25 (11.6)	15.7 (9.7, 21.7)	2.88 (1.80, 4.59)	<0.0001
Mucosal healingd (both endoscopy and histology)	54 (12.6)	8 (3.7)	8.9 (4.9, 12.9)	3.77 (1.76, 8.07)	<0.001

Data based on all randomized patients who received ≥1 dose of study treatment (intent-to-treat population). Missing data handled using non-responder imputation. p-Values based on two-sided Cochran–Mantel–Haenszel test.

^aRBS = 0, SFS ≤1 (plus ≥1-point reduction from baseline), and MES ≤1 without friability.

^bReduction in three-component Mayo score of ≥2 points and ≥35%, and reduction in RBS of ≥1 point or absolute RBS of ≤1 point.

^cDefined as MES ≤1 without friability.

^dEndoscopic improvement plus histologic remission (defined as no neutrophils in the epithelial crypts or lamina propria and no increase in eosinophils, no crypt destruction, and no erosions, ulcerations, or granulation tissue) in the same patient.

TNFi: tumor necrosis factor inhibitor; RBS: rectal bleeding subscore; SFS: stool frequency subscore; MES: mucosal endoscopy subscore.

Disclosure: WS (male) has received research grants from Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, AbbVie, Janssen, Takeda, Lilly, Celgene/Receptos, Pfizer, Prometheus Biosciences; consulting fees from AbbVie, Allergan, Amgen, Arena Pharmaceuticals, Avexegen Therapeutics, BeiGene, Boehringer Ingelheim, Celgene, Celltrion, Conatus, Cosmo, Escalier Biosciences, Ferring, Forbion, Genentech, Gilead Sciences, Gossamer Bio, Incyte, Janssen, Kyowa Kirin Pharmaceutical Research, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pfizer, Progenity, Prometheus Biosciences, Reistone, Ritter Pharmaceuticals, Alimentiv (formerly Robarts Clinical Trials, owned by Health Academic Research Trust, HART), Series Therapeutics, Shire, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, Takeda, Theravance Biopharma, Tigenix, Tillotts Pharma, UCB Pharma, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals; and stock or stock options from BeiGene, Escalier Biosciences, Gossamer Bio, Oppilan Pharma, Prometheus Biosciences, Progenity, Ritter Pharmaceuticals, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences. GD (male) has consulted for AbbVie, Ablynx, Amakem, AM Pharma, Avaxia, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Cosmo, Covidien/Medtronic, Ferring, Dr. Falk Pharma, EnGene, Galapagos, Genentech/Roche, Gilead, GlaxoSmithKline, Hospira, Immunic, Johnson & Johnson, Lycera, Medimetriks, Millennium/Takeda, Mitsubishi Pharma, Merck Sharp & Dohme, Mundipharma, Novo Nordisk, Otsuka, Pfizer, Prometheus Laboratories/Nestle, Protagonist, Receptos, Robarts Clinical Trials, Salix, Sandoz, SetPoint, Shire, Teva, Tigenix, Tillotts, TopiVert, Versant, Vifor; is a speaker for AbbVie, Biogen, Ferring, Johnson & Johnson, Merck Sharp & Dohme, Mundipharma, Norgine, Pfizer, Millennium/Takeda, Tillotts, Vifor; is a director at Robarts Clinical Trials; and is a shareholder at EnGene. SH (male) has consulted for Celgene, AbbVie, Janssen, UCB, Shire, Actavis, Salix, BMS, Merck Sharp & Dhome, Pfizer, Boehringer Ingelheim, Sanofi-Aventis, Ferring, Caremark. DW (male) has received research funding from AbbVie, Amgen, Elan, Given Imaging, Genentech, Janssen, Millennium, Pfizer, Prometheus, Celgene, UCB; has lectured for AbbVie, Janssen, Prometheus, Santarus, Salix, Takeda, UCB; and consulted for AbbVie, Genentech, Given Imaging, Janssen Prometheus, Salix, Takeda, UCB. IJ (male) has received honoraria as a speaker and consultant from AbbVie, Takeda, Goodwill, Krka, Abbott, Actavis, Merz Pharma, Ferring, Inothera Chouzy, Alvogen, Galenika, Hemofarm, and has received research funding from AbbVie, Janssen, Celgene, Sublimity, Celltrion. SG (male) has received research funding from AbbVie, GSK; is a lecturer for AbbVie, Pfizer, Takeda, Janssen, Ferring, MSD; and is a consultant for Pfizer, Novo Nordisk, BMS, Janssen, AbbVie, Takeda, Eli Lilly, Roche, Gilead, Galapagos, Celgene. AKP (female), SYH (male), JHL (male), LC (female), and KU (male) are employees of Bristol-Myers Squibb Company. SD (male) has received honoraria as a speaker, consultant, and/or advisory board member from AbbVie, Allergan, Biogen Idec, Boehringer Ingelheim, Celgene Corporation, Celltrion, Ferring, Hospira, Janssen, Johnson & Johnson, Merck, Merck Sharp & Dohme, Mundipharma, Pfizer, Sandoz, Takeda, Tigenix, UCB Pharma, Vifor. BF (male) has consulted for AbbVie, ActoGeniX, Albireo, Amgen, AstraZeneca, Avaxia Biologics, Baxter, Biogen Idec, Boehringer Ingelheim, BMS, Calypso, Celgene, Elan, EnGene, Ferring Pharma, Roche/Genentech, GiCare, Gilead, Given Imaging, GSK, Ironwood, Janssen, Johnson & Johnson, Lexicon, Lilly, Merck, Millennium, Nektar, Novo Nordisk, Pfizer, Prometheus, Protagonist, Sanofi, UCB, and is a director at Robarts Clinical Trials.

Reference

1. Sandborn WJ, et al. Ozanimod induction and maintenance treatment for ulcerative colitis. N Engl J Med 2016; 374: 1754–1762.

LB03 ERCP, EUS, luminal stenting and dilatation: Experience from a university teaching hospital in the UK during the COVID-19 pandemic

S Esmaily, CC Yau, D Dwarakanath, J Hancock, V Mitra

University Hospital North Tees, Gastroenterology, Stockton-on-Tees, UK

Contact e-mail address: shiranesmaily@doctors.org.uk

Introduction

In the UK, the COVID-19 pandemic began in mid-March 2020, peaked by late April, and the post-pandemic phase continued thereafter. The British Society of Gastroenterology has provided guidance for managing endoscopy services throughout this period. Currently, the UK is in the early recovery phase of restarting endoscopy post COVID-19 pandemic. At the beginning of the pandemic, a symptom-based questionnaire was used to screen patients for COVID-19 prior to their endoscopic procedures in our organisation. From 18 May 2020, all patients attending therapeutic endoscopic procedures at North Tees Hospital underwent a SARS-CoV-2 nasopharyngeal swab one to three days prior to therapeutic procedure, along with a screening questionnaire for COVID-19 symptoms. All procedures are vetted by a consultant prior to booking into a list.

Aims and methods: The study had the following aims:

1. To assess the number of patients with a positive SARS-CoV-2 nasopharyngeal swab in the 28 days following a procedure

2. To compare the rate of post-procedure positive swabs prior to and following the introduction of pre-procedure SARS-CoV-2 nasopharyngeal screening

3. To assess the KPIs for all therapeutic proceduresAll therapeutic procedures from 18 March to 31 July were included. The date 18 March was chosen, as it was the onset of the pandemic in the UK. All patients have been followed up for 30 days post procedure. A retrospective analysis of a prospectively maintained endoscopy database was carried out. Data collection included patient demographics, laboratory investigations, cross-sectional imaging, endoscopic intervention, trainee participation and 30-day post-procedure mortality. This project was carried out a service evaluation project.

Results

A total of 110 therapeutic procedures were performed between 18 March and 17 May. A total of 169 procedures were carried out from 18 May to 31 July.

Therapeutic Procedures Breakdown

	Pre-COVID swabbing		Post-COVID swabbing
	Inpatient	Outpatient	Inpatient	Outpatient
ERCP	23	31	55	37
EUS	5	29	7	50
Oesophageal stent	0	4	2	3
Duodenal stent	0	0	0	1
Oesophageal dilatation	1	16	4	12
Colonic stent	0	1	0	0

One patient who underwent an emergency colonic stent contracted COVID-19 eight days following their procedure. (Pre-procedure COVID swab was not standard practice at that time.) There were no COVID-positive swabs post procedure in the period where all patients were screened with a swab prior to procedure. Overall, CBD cannulation was achieved in 90.4% of procedures (132/146). A total of 82.2% (120/146) of ERCP procedures were done on a naïve papilla. The rate of CBD cannulation in naïve papilla was 89.2% (107/120). A total of 47.9% of ERCP (70/146) procedures were performed for stone disease (duct clearance rate 88.6%). A total of 91% (31/34) had a successful stent insertion in biliary stricture disease. Ninety-one EUS procedures were performed (63 diagnostic, 28 EUS biopsy (diagnostic yield 89%, three biopsies were negative for cancer but confirmed on biliary brushings during ERCP)). Nine patients underwent successful oesophageal stenting (100% technical and clinical success), 33 patients underwent successful oesophageal dilatation (100% technical and clinical success) and one patient underwent successful colonic decompression. Procedure-related mortality was 0.7% (2/279). Trainees were present in 47% of procedures.

Conclusion

Our study confirms that a high-quality therapeutic endoscopy service can be delivered safely during the COVID-19 pandemic in appropriately prioritised patients.

Disclosure: Nothing to disclose.

LB04 Palliation of malignant biliary strictures of main bile duct: Comparison of plastic stents, uncovered metal stents, partially covered metal stents and fully covered metal stents

F Pigò¹, G Masciangelo², S Mangiafico³, S Cocca¹, H Bertani¹, G Grande¹, S Russo², A Caruso¹, M Lupo¹, R Conigliaro¹

¹Azienda Ospedaliero Universitaria di Modena, Digestive Endoscopy – OCSAE, Modena, Italy

²Azienda Ospedaliero Universitaria di Modena, Digestive Endoscopy, Modena, Italy

³AOU Modena, Digestive Endoscopy, Modena, Italy

Contact e-mail address: pigo.flavia@aou.mo.it

Introduction

Plastic or metal stents are the treatment of choice for malignant biliary strictures unfit for surgery.

Aims and methods: The aim of the study was to compare the stent obstruction rate and patency time of plastic stent (PS), uncovered metal stents (USEMS), partially covered metal stents (PCSEMS) and fully covered metal stents (FCSEMS) in a cohort of patients palliated for malignant biliary stricture. All consecutive patients unfit for surgery with malignant biliary stricture treated with a stent placement were retrospectively enrolled in this study from 2015 to 2019. Cases with hilum involvement or with incomplete clinical information were excluded. Stent obstruction was defined as the presence of sludge/stone/neoplastic ingrowth inside the stent visible endoscopically or as a defect during cholangiography. Patency time was expressed as median and interquartile range and compared with ANOVA test.

Results

A total of 161 patients (66 male, mean age 77.5 years) were eligible for the study. In 69% of cases, malignant stricture was related to pancreatic neoplasm. Stricture was treated with PS in 48 cases, with USEMS in 41 cases, with PCSEMS in 28 cases and with FCSEMS in 44 cases. Median survival time was 222 (129–355), 153 (49–315), 149 (58–200) and 239 (94–379) days for PSs, USEMSs, PCSEMSs and FCSEMSs, respectively (p = 0.142). ERCP for stent obstruction was performed in 52% (95% CI 37–65) of cases for PSs, 24% (95% CI 13–40) of cases for USEMSs, 11% (95% CI 3–29) of cases for PCSEMSs and 16% (95% CI 7–30) of cases for FCSEMSs. Patency time of the stents was 65 (21–116) days for PSs, 216 (121–300) days for USEMSs, 146 (119–168) days for PCSEMSs and 136 (43–293) days for FCSEMSs (p<0.05 for PS vs. USEMSs, PCSEMSs and FCSEMSs). Migration occurred in two patients (4%; 95% CI 0–15) with PSs, no patients with USEMSs, one patient (4%; 95% CI 0–22) with PCSEMSs and seven patients (16%; 95% CI 8–30) with FCSEMSs.

Conclusion

PSs are not indicated for the treatment of malignant biliary strictures because of the short time of patency with respect to the survival time of patients. USEMSs, PCSEMSs and FCSEMSs have a similar patency rate and patency time, even if FCSEMSs are prone to migrate.

Disclosure: Nothing to disclose.

LB05 Risk and time pattern of recurrences after local endoscopic resection of T1 colorectal cancer: A meta-analysis

H Dang¹, N Dekkers¹, S Le Cessie², JE van Hooft¹, ME van Leerdam¹, PP Oldenburg¹, L Flothuis¹, JW Schoones³, AMJ Langers¹, JCH Hardwick¹, J van Der Kraan¹, JJ Boonstra¹

¹Leiden University Medical Center, Department of Gastroenterology and Hepatology, Leiden, The Netherlands

²Leiden University Medical Center, Department of Biomedical Data Sciences, Leiden, The Netherlands

³Leiden University Medical Center, Walaeus Library, Leiden, The Netherlands

Contact e-mail address: h.dang@lumc.nl

Introduction

Growing numbers of T1 CRC patients are being treated with local endoscopic resection only, and as a result, the need for optimization of surveillance strategies for these patients also increases. We aimed to estimate the cumulative incidence and time pattern of CRC recurrences for endoscopically treated T1 CRC patients.

Aims and methods: Using a systematic literature search in PubMed, EMBASE, Web of Science and Cochrane Library (from inception to 15 May 2020), we identified and extracted data from studies describing the cumulative incidence of local or distant CRC recurrence for T1 CRC patients treated with local endoscopic resection only. Pooled estimates were calculated using mixed-effect logistic regression models.

Results

Seventy-one studies with 5167 unique, endoscopically treated T1 CRC patients were included. The pooled cumulative incidence of any CRC recurrence was 3.3% (209 events; 95% CI 2.6–4.3%; I² = 54.9%), with local and distant recurrences being found at comparable rates (pooled incidences 1.9% and 1.6%, respectively). CRC-related mortality was observed in 42/2519 patients (35 studies; pooled incidence 1.7%, 95% CI 1.2–2.2%; I² = 0%), and the CRC-related mortality rate among patients with recurrence was 40.8% (42/103 patients). The vast majority of recurrences (95.6%) occurred within 72 months of follow-up. Pooled incidences of any CRC recurrence were 7.0% for high-risk T1 CRCs (28 studies; 95% CI 4.9–9.9%; I² = 48.1%) and 0.7% (36 studies; 95% CI 0.4–1.2%; I² = 0%) for low-risk T1 CRCs.

Conclusion

Our meta-analysis provides quantitative outcome measures which are relevant to guidelines on surveillance after local endoscopic resection of T1 CRC.

Disclosure: JJB is a consultant of Boston Scientific. JEvH is a consultant of Boston Scientific, Cook Medical and Medtronics, and received a research grant from Cook Medical. All other authors declare no potential conflicts of interest.

LB06 Long-term survival in oesophageal cancer after minimally invasive oesophagectomy compared to open oesophagectomy

E Gottlieb-Vedi¹, JH Kauppila^1,2, F Mattsson¹, M Lindblad¹, M Nilsson¹, P Lagergren^1,3, I Rouvelas¹, J Lagergren^1,4, FINEGO Group

¹Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden

²University of Oulu and Oulu University Hospital, Oulu, Finland

³Imperial College, London, UK

⁴King’s College, London, UK

Contact e-mail address: eivind.gottlieb@ki.se

Introduction

Minimally invasive oesophagectomy (MIO) is becoming an increasingly common approach in the surgical treatment of oesophageal cancer. A recent meta-analysis suggested 18% lower five-year all-cause mortality after MIO compared to open oesophagectomy (OO), but the quality of the included studies was limited.

Aims and methods: The aim of the study was to examine five-year survival in oesophageal cancer after MIO compared to OO. The design was population-based cohort study including almost all patients who underwent elective oesophagectomy for oesophageal cancer in Sweden or Finland in 2010–2016, with follow-up until 2020. Cox regression was used to provide hazard ratios (HRs) with 95% confidence intervals (CIs) of all-cause five-year mortality (main outcome) after MIO (hybrid or total) vs. OO. Adjustments were made for age, sex, co-morbidity, pathological tumour stage, histological tumour type, neoadjuvant chemo(radio)therapy, country and annual hospital volume of oesophagectomy.

Results

Among all 1264 patients, 470 (37.2%) underwent MIO and 794 (62.8%) underwent OO. MIO was associated with an 18% decreased risk of all-cause five-year mortality compared to OO (adjusted HR = 0.82, 95% CI 0.67–1.00; p = 0.048). The HR of all-cause five-year mortality was seemingly lower after total MIO compared to OO (adjusted HR = 0.77, 95% CI 0.60–0.98) than after hybrid MIO compared to OO (adjusted HR = 0.87, 95% CI 0.68–1.11).

Conclusion

This bi-national study indicates that MIO is associated with a higher five-year survival than OO in patients with oesophageal cancer, and that the survival benefit is greater after total MIO than hybrid MIO.

Disclosure: Nothing to disclose.

LB07 Sessile serrated adenoma/polyp (SSA/P) detection rates have improved over a four-year period, but have not improved further after a targeted educational intervention at an Australian tertiary health network

K Nalankilli^1,2, I Hartley¹, A Mack¹, Y Shao¹, CLW Suen³, S Vogrin², I Kronborg^1,2, A Moss^1,2

¹Western Health, Department of Gastroenterology, Melbourne, Australia

²University of Melbourne, Department of Medicine, Western Health, Melbourne, Australia

³Austin Health, Department of Gastroenterology, Melbourne, Australia

Contact e-mail address: kumanan.nalankilli@gmail.com

Introduction

The sessile serrated adenoma detection rate (SSADR) for colonoscopists is increasingly considered as a quality marker for effective colonoscopy. Hospitals are now required to monitor the SSADR of their colonoscopists as per recent Australian standards. The Australian colonoscopy recertification program recommends a minimum SSADR of 4%. Therefore, educational programmes that aim to improve SSADR are highly relevant.

Aims and methods: We aimed to (1) retrospectively compare the current ADR and SSADR of different categories of colonoscopists at a large Australian tertiary health network, with a previously collected data series of these rates from 2015; and (2) prospectively assess the impact of a brief targeted educational intervention on the SSADR for these same practitioners. All colonoscopies performed over a seven-month period (1 July 2018–31 January 2019) were reviewed retrospectively. A previous similarly collected data set from 1 July 2015 to 31 December 2015 was used as a control cohort. During February 2019, an educational session comprising a 30-minute PowerPoint presentation on recognising endoscopic features of SSA/P and practical tips that may improve one’s SSADR, including video examples, was given to all practising gastroenterologists and colorectal surgeons in our network. For reinforcement, the content of the presentation was summarised in an A3-sized poster and prominently displayed in six endoscopy suites at three separate sites within our health network. Following this, data were collected prospectively from March 2019 to September 2019, including bowel preparation quality, caecal intubation rates, category of colonoscopist and indication for colonoscopy. The ADR and SSADR were captured by reviewing histopathology results.

Results

We analysed 1763 colonoscopies from July 2018 to January 2019 (pre-intervention) and 1843 from March 2019 to September 2019 (post intervention). Overall detection rates pre- and post-intervention were: ADR 40.5% vs. 42.4% (p = 0.25); SSADR 9.2% vs. 9.3% (p = 0.95). Those for non-interventional gastroenterologists were: ADR 34.8% vs. 38.8% (p = 0.23); SSADR 6.7% vs. 7.8% (p = 0.60)). Those for interventional gastroenterologists were: ADR 50.0% vs. 48.9% (p = 0.82); SSADR 17.7% vs. 15.2% (p = 0.40). Those for nurse endoscopists were ADR 52.3% vs. 53.8% (p = 0.79); SSADR 9.9% vs. 10.3% (p = 1). Those for colorectal surgeons were ADR 32.1% vs. 33.1% (p = 0.76); SSADR 6.2% vs. 6.3% (p = 1). Those for general surgeons were ADR 26.7% vs. 25.5% (p = 1); SSADR 5% vs. 5.9% (p = 1). There were no differences in bowel preparation quality, caecal intubation rate or indications. Compared to the control cohort of 1562 colonoscopies between 1 July 2015 and 31 December 2015, overall baseline SSADR had improved significantly (6% vs. 9.3%; p<0.05). General surgeons had significantly improved their baseline ADR (ADR 15% vs. 26%; p<0.05) and SSADR (0% vs. 5.9%; p<0.05). Colorectal surgeons (ADR 25% vs. 33%, p<0.05; SSADR 4% vs. 6.2%) and nurse endoscopists (38% vs. 53%; p<0.05) had a significantly improved baseline ADR.

Conclusion

The overall ADR and SSADR recorded in our health network are well above the recommended detection rates. There is a statistically significant improvement in overall SSADR over a four-year period between 2015 and 2019, likely due to increased awareness and accumulating experience in detecting SSA. However, a brief educational intervention did not further improve SSADR. This may be because the intervention was too brief to induce behaviour change or because once an adequate benchmark is reached, it is difficult to enhance detection rates further. Further studies into effective but practical methods to increase SSADR are required.

Disclosure: Nothing to disclose.

LB08 Etrolizumab as induction and maintenance therapy in patients with ulcerative colitis previously exposed to anti-tumor necrosis factor agent: The randomized, Phase III HICKORY trial

L Peyrin-Biroulet¹, AL Hart², P Bossuyt³, M Long⁴, M Allez⁵, P Juillerat⁶, A Armuzzi⁷, EV Loftus Jr ⁸, E Ostad-Saffari⁹, A Scalori⁹, YS Oh¹⁰, S Tole¹⁰, A Chai¹⁰, J Pulley⁹, S Lacey⁹, W Sandborn¹¹, on behalf of the HICKORY Study Group; Drs. Peyrin-Biroulet and Hart contributed equally to this work

¹Université de Lorraineo-Gastroenterology, Nancy, France

²St Mark’s Academic Institute, London, UK

³Imelda GI Clinical Research Center, Imelda General Hospital, Bonheiden, Belgium

⁴University of North Carolina, Chapel Hill, USA

⁵Hôpital Saint-Louis, APHP, Université de Paris, Paris, France

⁶Inselspital, Bern University Hospital, Bern, Switzerland

⁷Catholic University of the Sacred Heart, Rome, Italy

⁸Mayo Clinic College of Medicine, Rochester, USA

⁹Roche Products Limited, Welwyn Garden City, UK

¹⁰Genentech, Inc., South San Francisco, USA

¹¹University of California, San Diego, La Jolla, USA

Contact e-mail address: peyrinbiroulet@gmail.com

Introduction

Etrolizumab, an anti-β7 monoclonal antibody, binds α4β7 and αEβ7 integrins to inhibit both trafficking of immune cells into the gut and their inflammatory effects on the gut lining. We evaluated the efficacy and safety of etrolizumab vs. placebo (PBO) for induction and maintenance of remission in patients (pts) with moderately to severely active ulcerative colitis (UC) previously treated with anti-tumor necrosis factor agent (aTNF).

Aims and methods: HICKORY (NCT02100696) was a randomized, double-blind, PBO-controlled Phase III study of etrolizumab in pts with moderately to severely active UC previously exposed to aTNF. Pts received subcutaneous etrolizumab 105 mg every four weeks as induction treatment, either open-label (cohort 1) or blinded vs. PBO in a 4:1 randomization scheme (cohort 2). Etrolizumab-treated pts (cohorts 1 and 2) with a clinical response (Mayo Clinic total score (MCS) with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore (RBS) or absolute RBS of 0–1) at week 14 were rerandomized 1:1 to etrolizumab or PBO as maintenance treatment. The induction primary endpoint was remission (MCS ≤2 with individual subscores ≤1 and an RBS of 0) at week 14. The maintenance primary endpoint was remission at week 66 in pts with clinical response at week 14. Induction data from the pivotal cohort 2 and maintenance are presented here (cohort 1 induction was previously presented¹).

Results

The study enrolled 609 pts (cohort 1: n = 130; cohort 2: n = 479 (etrolizumab, n = 384; PBO, n = 95)). At week 14, etrolizumab clinical responders were randomized to etrolizumab (n = 117) or PBO (n = 115); 27 PBO cohort 2 pts were sham randomized to continue PBO in maintenance. Sixty-three (53.8%) etrolizumab/etrolizumab pts and 45/115 (39.1%) etrolizumab/PBO pts completed week 66. During induction, cohort 2 treatment arms were balanced: at baseline, median duration of disease was seven years, median MCS was 9, and 45.6% of etrolizumab pts and 44.2% of PBO pts were aTNF primary/secondary nonresponders. At week 14, the primary efficacy endpoint for induction was met: remission was achieved in 18.5% of etrolizumab pts vs. 6.3% of PBO pts (p = 0.0033). Clinical response was achieved in 45.8% of etrolizumab pts vs. 31.6% of PBO pts (p = 0.0241). At week 66, etrolizumab did not significantly improve remission compared with PBO (24.1% vs. 20.2%, p = 0.4956). However, rates of endoscopic improvement, endoscopic remission, and histologic remission at week 66 were nominally statistically significant for etrolizumab vs. PBO (Table). For induction and maintenance, adverse events were comparable between etrolizumab and PBO, and most were grade 1/2. There were no deaths or cases of progressive multifocal leukoencephalopathy.

Abstract No: LB08.

Results of Primary and Key Secondary Efficacy Endpoints During Induction (Week 14) and Maintenance (Week 66) Treatment with Etrolizumab and PBO

	Induction mITT—Week 14				Maintenance mITT—Week 66
	PBO N=95	Etro N=384	Treatment difference (95% CI)	p-Value	PBOa N=114	Etro N=112	Treatment difference (95% CI)	p-Value
Remission, n (%)	6 (6.3)	71 (18.5)	12.2 (4.0, 17.7)	0.0033	23 (20.2)	27 (24.1)	3.8 (–7.1, 14.6)	0.4956
Clinical response, n (%)	30 (31.6)	176 (45.8)	14.3 (3.2, 24.1)	0.0241	NE	NE	NE	NE
Endoscopic improvement,b n (%)	24 (25.3)	128 (33.3)	8.1 (–2.5, 17.2)	0.1605	24 (21.1)	40 (35.7)	14.5 (2.7, 25.8)	0.0153c
CS-free remission in pts receiving baseline CS,d n/N (%)	NE	NE	NE	NE	6/55 (10.9)	10/54 (18.5)	7.4 (–6.2, 21.2)	0.2787c
Endoscopic remission,e n (%)	9 (9.5)	66 (17.2)	7.6 (–1.2, 13.7)	0.3881	13 (11.4)	26 (23.2)	11.9 (1.9, 21.7)	0.0174c
Histologic remission,f n/N (%)	20/80 (25.0)	92/310 (29.7)	4.9 (–6.8, 14.7)	0.5879	13/92 (14.1)	28/91 (30.8)	16.8 (4.4, 28.4)	0.0073c

^aExcludes placebo-treated patients from cohort 2 sham-randomized to placebo during maintenance.

^bMayo Clinic endoscopic subscore ≤1.

^cSince the primary endpoint was not met, no other key secondary endpoints were formally tested. Nominal p-values are shown here.

^dIn patients receiving baseline CS, remission with no CS use for 24 weeks before week 66.

^eMayo Clinic endoscopic subscore=0.

^fNancy Histological Index ≤1.

CS: corticosteroid; Etro: etrolizumab; mITT: modified intention-to-treat population; NE: not evaluated; PBO: placebo.

Conclusion

HICKORY met the induction primary endpoint of remission at week 14. Despite nominally statistically significant benefits with etrolizumab vs. PBO in endoscopic improvement, endoscopic remission, and histologic remission at week 66, the primary endpoint of remission at week 66 among week 14 clinical responders was not met. No unexpected safety signals occurred.

Disclosure: LP-B reports personal fees from AbbVie, Janssen, Genentech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Boehringer Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestle, Enterome, Allergan, MSD, Roche, Arena, Gilead, Hikma, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius, Oppilan Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera; grants from Abbvie, MSD, Takeda; other from CTMA (outside the submitted work). AH reports personal fees from Roche, AbbVie (during the conduct of the study), Arena, Celgene, Celltrion, Falk, Ferring, Janssen, Napp Pharmaceuticals, Pfizer, Pharmacosmos, Takeda (outside the submitted work). PB reports personal fees from Roche/Genetech during the conduct of the study; personal fees from Roche/Genentech, Takeda, MSD, Sandoz, Celltrion, Pentax, BMS, Guidepoint; grants and personal fees from Abbvie, Pfizer, Mylan, Mundipharma, Janssen (outside the submitted work). ML reports personal fees from AbbVie; grants and personal fees from Takeda, Pfizer; personal fees from Janssen, Target PharmaSolutions, Ucb, Salix, Valeant, Gilead, Prometheus (outside the submitted work). MA reports grants from Janssen, Genentech; personal fees from Amgen, Biogen, Boehringer Ingelheim, Celgene, Ferring, Genentech, Janssen Pfizer, Takeda, Tillots, Roche (outside the submitted work). PJ has nothing to disclose. AA reports personal fees from Abbvie, Allergan, Amgen, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Ferring, Gilead, Janssen, Lilly, Mitsubishi-Tanabe, Mylan, Nikkiso, Roche, Samsung Bioepis, Sandoz, Tigenix; grants and personal fees from MSD, Pfizer, Takeda (outside the submitted work). EL reports grants and personal fees from Genentech (during the conduct of the study), AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Pfizer, Takeda, UCB; grants from Robarts Clinical Trials; personal fees from Allergan, Boehringer Ingelheim, Celltrion Healthcare, Eli Lilly (outside the submitted work); and Chief Medical Editor, Healio Gastroenterology and Liver Disease (SLACK, Inc.). EO-S has nothing to disclose. YSO reports he is an employee of Roche, the company sponsoring the study, and owns Roche stock as part of his compensation. ST is an employee of Genentech and Roche stockholder. AC reports that she is an employee of Genentech, a member of the Roche Group, and that she owns Roche stock as an employee. JP is an employee of Roche Products Ltd. SL reports other from Roche Genussscheine (nonvoting shares; outside the submitted work). BS reports grants, personal fees and other from Genentech/Roche (during the conduct of the study); grants and personal fees from Abbvie, Amgen; personal fees from Allergan, Arena Pharmaceuticals, Avexegen Therapeutics, Biogen Idec, Boehringer Ingelheim, Bristol Meyers Squibb, Celltrion, Conatus, Cosmo Technologies, Ferring Pharmaceuticals, Forbion, Forward Pharma; personal fees and other from Gossamer Bio, Immune Pharmaceuticals, Incyte, Kyowa Hakko Kirin Pharma, Landos Biopharma, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Otsuka, Paul Hastings, Reistone, Series Therapeutics, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, Theravance Biopharma, Tigenix, Tillotts Pharma, UCB Pharma, Vivelix Pharmaceuticals, Vimalan Biosciences, BeiGene, Escalier Biosciences, Oppilan Pharma; other from Ventyx Biosciences; grants from Atlantic Pharmaceuticals; grants and personal fees from Janssen, Celgene, Genentech, Gilead Sciences, Lilly, Pfizer, Progenity, Robarts Clinical Trials (owned by Health Academic Research Trust or HART), Salix Pharmaceuticals, Shire, Takeda; grants, personal fees and other from Prometheus Biosciences (merger of Precision IBD and Prometheus Laboratories); personal fees and other from Ritter Pharmaceuticals (outside the submitted work) and Spouse: Opthotech—consultant, stock options; Progenity—consultant, stock; Oppilan Pharma—employee, stock options; Escalier Biosciences—employee, stock options; Prometheus Biosciences (merger of Precision IBD and Prometheus Laboratories)—employee, stock options; Ventyx Biosciences – employee, stock options; Vimalan Biosciences—employee, stock options. AS reports other from Roche (outside the submitted work).

References

1. Peyrin-Biroulet L, et al. Etrolizumab induction therapy improved endoscopic score, patient-reported outcomes, and inflammatory biomarkers in patients with moderate to severe uc who had failed tnf antagonist therapy: results from the hickory open-label induction (oli) trial. United European Gastroenterol J 2017; 5: 1138–1139.

LB09 Etrolizumab compared with adalimumab or placebo as induction therapy for ulcerative colitis: Results from the randomized, Phase III HIBISCUS I and II trials

I Dotan^1,2, J Panés³, A Duvall⁴, Y Bouhnik⁵, G Radford-Smith⁶, PDR Higgins⁷, DS Mishkin⁸, P Arrisi⁹, A Scalori⁹, YS Oh¹⁰, S Tole¹⁰, A Chai¹⁰, K Chamberlain-James⁹, S Lacey⁹, J McBride¹⁰, DT Rubin¹¹, HIBISCUS I and II Study Group; Drs. Dotan and Panés contributed equally to this work

¹Rabin Medical Center, Petah Tikva, Israel

²Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

³Hospital Clinic Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain

⁴Tyler Research Institute, Tyler, USA

⁵Inserm et Université Paris Diderot, Paris, France

⁶Royal Brisbane and Women’s Hospital, Herston, Australia

⁷University of Michigan, Ann Arbor, USA

⁸Atrius Health, Boston, USA

⁹Roche Products Limited, Welwyn Garden City, UK

¹⁰Genentech, Inc., South San Francisco, USA

¹¹University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, USA

Contact e-mail address: irisdo@clalit.org.il

Introduction

Etrolizumab, an anti-β7 monoclonal antibody, binds α4β7 and αEβ7 integrins to inhibit both trafficking of immune cells into the gut and their inflammatory effects on the gut lining. We evaluated the safety and efficacy of etrolizumab as induction therapy for active ulcerative colitis (UC) compared with placebo and with adalimumab in patients naive to anti-tumor necrosis factor (aTNF) agents.

Aims and methods: Two identical multicenter, placebo-controlled, double-blind, double-dummy Phase III studies, HIBISCUS I (NCT02163759) and HIBISCUS II (NCT02171429), randomized aTNF-naive patients with moderately to severely active UC to subcutaneous (SC) etrolizumab 105 mg once every four weeks, SC adalimumab (160/80/40 mg at weeks 0/2/4, 6, and 8, respectively), or placebo in a 2:2:1 ratio. The primary endpoint, analyzed separately for the two studies, was induction of remission at week 10 with etrolizumab compared with placebo. Remission was defined as Mayo Clinic total score (MCS) ≤2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Key secondary endpoints included endoscopic improvement at week 10 for etrolizumab vs. placebo in each study and a pre-specified pooled analysis of remission at week 10 for etrolizumab vs. adalimumab.

Results

A total of 716 patients were randomized and treated: for HIBISCUS I (N = 358) and II (N = 358), respectively, 144 and 143 received etrolizumab; 142 and 143 received adalimumab; 72 and 72 received placebo. Demographics and baseline disease characteristics were balanced across treatment arms and comparable between studies. For all patients, median age was 38 years, median duration of disease was 3.9 years, and median MCS was 9. In HIBISCUS I, 28/144 (19.4%) patients treated with etrolizumab and 5/72 (6.9%) patients treated with placebo achieved remission at week 10 (p = 0.0173). In HIBISCUS II, 26/143 (18.2%) patients treated with etrolizumab and 8/72 (11.1%) patients treated with placebo achieved remission at week 10 (p = 0.1729). In the pooled analysis of HIBISCUS I and II, remission rates at week 10 were 54/287 (18.8%) for etrolizumab and 67/285 (23.5%) for adalimumab (nominal p = 0.1341). Results of additional key secondary endpoints are shown in the Table. Adverse events (AEs) were comparable across the three arms and both studies, and most AEs were nonserious and grade 1/2. In HIBISCUS I and II, 15/287 (5.2%) patients on etrolizumab, 6/285 (2.1%) on adalimumab, and 7/144 (4.9%) on placebo reported ≥1 serious AE. There were no deaths related to study drug or cases of progressive multifocal leukoencephalopathy.

Abstract No: LB09Table 1.

Results of Primary and Key Secondary Efficacy Endpoints at Week 10

	HIBISCUS I ( N=358)			HIBISCUS II ( N=358)			Pooled HIBISCUS I and II ( N=716)
Week 10 endpoint	Placebo (N=72)	Etrolizumab (N=144)	Adjusted p-valuea	Placebo (N=72)	Etrolizumab (N=143)	Nominal p-valueb	Adalimumab (N=285)	Etrolizumab (N=287)	Nominal p-value
Remission, n (%)	5 (6.9)	28 (19.4)	0.0173	8 (11.1)	26 (18.2)	0.1729a	67 (23.5)	54 (18.8)	0.1341
Endoscopic improvement,c n (%)	16 (22.2)	58 (40.3)	0.0173	22 (30.6)	57 (39.9)	0.1779	108 (37.9)	115 (40.1)	0.6280
Clinical response,d n (%)	36 (50.0)	82 (56.9)	0.4434	28 (38.9)	75 (52.4)	0.0501	152 (53.3)	157 (54.7)	0.7788
Histologic remission,e n/N (%)	10/62 (16.1)	51/120 (42.5)	0.0173	13/62 (21.0)	33/108 (30.6)	0.1705	84/230 (36.5)	84/228 (36.8)	0.9379
Endoscopic remission,f n (%)	5 (6.9)	30 (20.8)	0.1347 (0.0098)	6 (8.3)	28 (19.6)	0.0315	67 (23.5)	58 (20.2)	0.3011

^aMultiplicity-controlled (i.e. adjusted) p-values are displayed. For some key secondary endpoints, the nominal p-value has been included in parentheses.

^bSince the primary endpoint was not met, no key secondary endpoints were formally tested. Nominal p-values are shown here.

^cMayo Clinic endoscopic subscore ≤1.

^dMCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1.

^eNancy Histological Index ≤1.

^fMayo Clinic endoscopic subscore=0.

Conclusion

Etrolizumab induced remission, endoscopic improvement, and histologic remission at week 10 vs. placebo in a significant proportion of patients in HIBISCUS I. Despite nominally statistically significant benefit of etrolizumab vs. placebo in endoscopic remission in HIBISCUS II, the primary endpoint of remission at week 10 was not met. Pooled analyses did not show superiority of etrolizumab over adalimumab for week 10 endpoints. Etrolizumab treatment was well tolerated in aTNF-naive patients with moderately to severely active UC.

Disclosure: ID reports personal fees from Janssen, AbbVie, Takeda, Pfizer, Roche/Genentech, Neopharma, Gilead, Celltrion, Rafa Laboratories, Arena, Sublimity, Nestle, DSM, Abbott, Sandoz, Celgene/BMS; and other from Falk Pharmacy (outside the submitted work). JP reports consulting fees or honoraria from AbbVie, Boehringer Ingelheim, Celgene, Genentech, Roche, GSK, Janssen, MSD, Oppilan, Takeda, Theravance, TiGenix, Arena, Nestle, Pfizer, Progenity, AbbVie, Takeda; payment for lectures, including service on speakers’ bureaus, from Abbott, MSD, Takeda, Janssen, Pfizer, Roche, Biogen; and payment for development of educational presentations from Abbott, MSD, Roche, Pfizer. AD has nothing to disclose. YB reports consulting for AbbVie, Amgen, Biogaran, Biogen, Boehringer Ingelheim, Celltrion, Ferring, Fresenius Kabi, Gilead, Hospira, Janssen, Lilly, Mayoly Spindler, Merck, MSD, Norgine, Pfizer, Roche, Sandoz, Sanofi, Shire, Takeda, UCB; and grants from AbbVie, MSD, Ferring, Takeda, Hospira, Janssen. GR-S reports other from Janssen Australia, Ferring Australia, Pfizer, AbbVie, Takeda; and grants from Shire and Janssen Australia (outside the submitted work). PH reports that he is a site investigator for the etrolizumab Phase III clinical studies; funding for this research was provided by Roche, and third-party medical writing support was provided by ApotheCom (San Francisco, CA) and was funded by Roche. DM reports consulting for GI Reviewers. PA, AS, and JMcB are employees of and shareholders in Roche. YSO, ST, and AC are employees of and shareholders in Genentech/Roche. KC-J and SL report other from Roche Genussscheine (nonvoting shares) outside the submitted work. DR reports grants and personal fees from AbbVie, Genentech/Roche, Janssen Pharmaceuticals, Prometheus Laboratories, Shire, Takeda; and personal fees from AbGenomics, Allergan, Biomica, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene/Syneos, Check-Cap, Dizal Pharmaceuticals, GalenPharma/Atlantica, Gilead Sciences, Ichnos Sciences (formerly Glenmark Pharmaceuticals), GlaxoSmithKline, InDex Pharmaceuticals, Lilly, Narrow River Management, Pfizer, Reistone; and personal fees from Techlab (outside the submitted work).

LB10 Ozanimod as maintenance therapy in patients with moderate-to-severe ulcerative colitis: Results from the Phase III, randomized, double-blind, placebo-controlled True North study

S Danese¹, BG Feagan², DC Wolf³, SB Hanauer⁴, I Jovanovic⁵, S Ghosh⁶, A Petersen⁷, SY Hua⁷, JH Lee⁷, L Charles⁷, D Chitkara⁷, W Sandborn⁸, G D’Haens⁹

¹Humanitas Clinical and Research Center, Inflammatory Bowel Diseases Center, Milan, Italy

²Western University, London, Canada

³Atlanta Gastroenterology Associates, Center for Crohn’s Disease and Ulcerative Colitis, Atlanta, USA

⁴Feinberg School of Medicine, Chicago, USA

⁵University Hospital Medical Centre Bezanijska Kosa, Division of Gastroenterology, Belgrade, Serbia

⁶University of Calgary, Alberta, Canada

⁷Bristol-Myers Squibb Company, Princeton, USA

⁸University of California San Diego, Division of Gastroenterology, La Jolla, USA

⁹Amsterdam University Medical Center, Inflammatory Bowel Disease Center, Amsterdam, The Netherlands

Contact e-mail address: sdanese@hotmail.com

Introduction

Ozanimod demonstrated efficacy and safety for ≤32 weeks of treatment in patients with moderate-to-severe ulcerative colitis (UC) in the randomized, Phase II TOUCHSTONE study.¹ Here, we report the efficacy and safety of ozanimod vs. placebo at week 52 in the maintenance period of a randomized, double-blind, Phase III study in patients with moderate-to-severe UC (True North; NCT02435992). Results from the 10-week induction period of this study are reported separately (Sandborn et al., abstract LB02).

Aims and methods: Adult patients with clinical response after 10 weeks of ozanimod induction therapy in double-blind and open-label cohorts were eligible to be re-randomized 1:1 to double-blind maintenance treatment with ozanimod HCl 1 mg/day (equal to ozanimod 0.92 mg) or matching placebo. Patients were stratified by clinical remission status and corticosteroid use at week 10. Endpoints were assessed at week 52 and tested sequentially via closed hierarchical procedure. The primary endpoint was the proportion of patients in clinical remission per three-component Mayo score. Ranked key secondary endpoints (defined in the Table) were proportions of patients with clinical response, endoscopic improvement, maintenance of clinical remission, corticosteroid-free remission, mucosal healing (both endoscopy and histology), and durable clinical remission. Data were also analyzed by prior tumor necrosis factor inhibitor (TNFi) use.

Results

A total of 457 patients were re-randomized to maintenance treatment with either ozanimod (n = 230) or placebo (n = 227). Of these, 80% and 54.6% of patients who received ozanimod and placebo, respectively, completed the study; disease relapse (13.5% ozanimod, 33.9% placebo) was the most common reason for discontinuation. All primary and key secondary efficacy endpoints showed statistically significant improvements with ozanimod vs. placebo at week 52 (Table). Ozanimod resulted in a significantly higher clinical remission rate vs. placebo (37.0% vs. 18.5%; difference: 18.6% (95% CI 10.8–26.4); p<0.0001). Significant results were also observed in all key secondary endpoints; clinical response (p<0.0001), endoscopic improvement (p<0.001), maintenance of remission (p<0.0047), corticosteroid-free remission (p<0.001), mucosal healing (p<0.001), and durable remission (p = 0.003). Clinical remission and response also improved with ozanimod regardless of previous TNFi use. The most common treatment-emergent adverse events (TEAEs) for ozanimod vs. placebo, respectively, were alanine aminotransferase increase (4.8% vs. 0.4%; no serious events), and headache (3.5% vs. 0.4%). Frequency of possible, probable, or related serious TEAEs was low (≤1% in both groups).

Conclusion

Patients with moderate-to-severe UC treated with ozanimod for up to 52 weeks in True North demonstrated clinically relevant and statistically significant benefits on clinical, endoscopic, and mucosal healing endpoints. No new safety signals were observed for ozanimod.

Abstract No: LB10.

Efficacy Results at Week 52

Endpoint	Ozanimod → Ozanimod n (%) (N = 230)	Ozanimod → Placebo n (%) (N = 227)	Percent difference (95% CI)	Odds ratio (95% CI)	p-Value
Clinical remissiona	85 (37.0)	42 (18.5)	18.6 (10.8, 26.4)	2.76 (1.77, 4.29)	<0.0001
Prior TNFi therapy	n = 76 22 (28.9)	n = 69 7 (10.1)	18.4 (6.2, 30.6)	3.74 (1.44, 9.71)	0.0053
Clinical responseb	138 (60.0)	93 (41.0)	19.2 (10.4, 28.0)	2.27 (1.54, 3.33)	<0.0001
Prior TNFi therapy	n = 76 42 (55.3)	n = 69 17 (24.6)	30.4 (15.8, 45.1)	4.15 (2.00, 8.78)	0.0002
Endoscopic improvementc	105 (45.7)	60 (26.4)	19.4 (11.0, 27.7)	2.48 (1.65, 3.72)	<0.001
Maintenance of clinical remissiond	n = 79 41 (51.9)	n = 75 22 (29.3)	22.4 (7.4, 37.4)	2.62 (1.34, 5.11)	0.0047
Corticosteroid free remissione	73 (31.7)	38 (16.7)	15.2 (7.8, 22.6)	2.56 (1.60, 4.09)	<0.001
Mucosal healingf (both endoscopy and histology)	68 (29.6)	32 (14.1)	15.6 (8.2, 22.9)	2.64 (1.64, 4.26)	<0.001
Durable remissiong	41 (17.8)	22 (9.7)	8.2 (2.8, 13.6)	2.65 (1.38, 5.06)	0.003

Data based on all randomized patients who received ≥1 dose of study treatment (intent-to-treat population). Missing data handled using non-responder imputation. p-Values based on two-sided Cochran–Mantel–Haenszel test.

^aRBS = 0, SFS ≤1 (plus ≥1-point reduction from baseline), and MES ≤1 without friability.

^bReduction in three-component Mayo score of ≥2 points and ≥35%, and reduction in RBS of ≥1 point or absolute RBS of ≤1 point.

^cDefined as MES ≤1 without friability.

^dClinical remission at 52 weeks in the subset of patients who were in remission at week 10.

^eClinical remission at 52 weeks while off corticosteroids for ≥12 weeks.

^fEndoscopic improvement plus histologic remission (defined as no neutrophils in the epithelial crypts or lamina propria and no increase in eosinophils, no crypt destruction, and no erosions, ulcerations, or granulation tissue) in the same patient.

^gRemission at weeks 10 and 52 in all patients who entered the maintenance phase.

UC: ulcerative colitis; RBS: rectal bleeding subscore; SFS: stool frequency subscore; MES: mucosal endoscopy subscore; TNFi: tumor necrosis factor inhibitor.

Disclosure: SD (male): AbbVie, Allergan, Biogen Idec, Boehringer Ingelheim, Celgene Corporation, Celltrion, Ferring, Hospira, Janssen, Johnson & Johnson, Merck, Merck Sharp & Dohme, Mundipharma, Pfizer, Sandoz, Takeda, Tigenix, UCB Pharma, Vifor. BF (male): AbbVie, ActoGeniX, Albireo, Amgen, AstraZeneca, Avaxia Biologics, Baxter, Biogen Idec, Boehringer Ingelheim, BMS, Calypso, Celgene, Elan, EnGene, Ferring Pharma, Roche/Genentech, GiCare, Gilead, Given Imaging, GSK, Ironwood, Janssen, Johnson & Johnson, Lexicon, Lilly, Merck, Millennium, Nektar, Novo Nordisk, Pfizer, Prometheus, Protagonist, Sanofi, UCB, and a director at Robarts Clinical Trials. DW (male): AbbVie, Amgen, Elan, Given Imaging, Genentech, Janssen, Millennium, Pfizer, Prometheus, Celgene, Santarus, Salix, Takeda, UCB. SH (male): Celgene, AbbVie, Janssen, UCB, Shire, Actavis, Salix, BMS, Merck Sharp & Dhome, Pfizer, Boehringer Ingelheim, Sanofi-Aventis, Ferring, Caremark—consultant. IJ (male): honoraria as a speaker and consultant from AbbVie, Takeda, Goodwill, Krka, Abbott, Actavis, Merz Pharma, Ferring, Inothera Chouzy, Alvogen, Galenika, Hemofarm, and research funding from AbbVie, Janssen, Celgene, Sublimity, Celltrion. SG (male) has received research funding from AbbVie, GSK; is a lecturer for AbbVie, Pfizer, Takeda, Janssen, Ferring, MSD; and a consultant for Pfizer, Novo Nordisk, BMS, Janssen, AbbVie, Takeda, Eli Lilly, Roche, Gilead, Galapagos, Celgene. AKP (female), SYH (male), JHL (male), LC (female), DC are employed by Bristol-Myers Squibb. WS (male): Research grants from Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, AbbVie, Janssen, Takeda, Lilly, Celgene/Receptos, Pfizer, Prometheus Biosciences; consulting fees from AbbVie, Allergan, Amgen, Arena Pharmaceuticals, Avexegen Therapeutics, BeiGene, Boehringer Ingelheim, Celgene, Celltrion, Conatus, Cosmo, Escalier Biosciences, Ferring, Forbion, Genentech, Gilead Sciences, Gossamer Bio, Incyte, Janssen, Kyowa Kirin Pharmaceutical Research, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pfizer, Progenity, Prometheus Biosciences, Reistone, Ritter Pharmaceuticals, Alimentiv (formerly Robarts Clinical Trials, owned by Health Academic Research Trust, HART), Series Therapeutics, Shire, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, Takeda, Theravance Biopharma, Tigenix, Tillotts Pharma, UCB Pharma, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals; and stock or stock options from BeiGene, Escalier Biosciences, Gossamer Bio, Oppilan Pharma, Prometheus Biosciences, Progenity, Ritter Pharmaceuticals, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences. GD (male): AbbVie, Ablynx, Amakem, AM Pharma, Avaxia, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Cosmo, Covidien/Medtronic, Ferring, Dr. Falk Pharma, EnGene, Galapagos, Genentech/Roche, Gilead, GlaxoSmithKline, Hospira, Immunic, Johnson & Johnson, Lycera, Medimetriks, Millennium/Takeda, Mitsubishi Pharma, Merck Sharp & Dohme, Mundipharma, Novo Nordisk, Otsuka, Pfizer, Prometheus Laboratories/Nestle, Protagonist, Receptos, Robarts Clinical Trials, Salix, Sandoz, SetPoint, Shire, Teva, Tigenix, Tillotts, TopiVert, Versant, Vifor—consultant; AbbVie, Biogen, Ferring, Johnson & Johnson, Merck Sharp & Dohme, Mundipharma, Norgine, Pfizer, Millennium/Takeda, Tillotts, Vifor—speaker; Robarts Clinical Trials—director; EnGene—shareholder.

References

1. Sandborn WJ, Feagan BG, Wolf DC, et al. Ozanimod induction and maintenance treatment for ulcerative colitis. N Engl J Med 2016; 374: 1754–1762.

LB11 Clinical and endoscopic response to treat-to-target versus standard of care in Crohn’s disease patients treated with ustekinumab: Week 48 results of the STARDUST trial

S Danese¹, S Vermeire², GR D’Haens³, J Panés⁴, A Dignass⁵, FJ Magro Dias^6,7, M Nazar⁸, M Le Bars⁹, M Lahaye¹⁰, L Ni¹¹, F Lavie⁹, I Bravat๲, S Sloan¹³, M Daperno¹⁴, M Lukas¹⁵, A Armuzzi¹⁶, M Lowenberg¹⁷, DR Gaya¹⁸, L Peyrin-Biroulet¹⁹

¹Humanitas University, Gastrointestinal Immunopathology, Milan, Italy

²University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium

³Academic Medical Centre, University of Amsterdam, Inflammatory Bowel Disease Centre, Amsterdam, The Netherlands

⁴Hospital Clinic of Barcelona, CIBERehd, Department of Gastroenterology, Barcelona, Spain

⁵Agaplesion Markus Krankenhaus, Medizinische Klinik I, Frankfurt/Main, Germany

⁶Institute for Molecular and Cell Biology, Faculty of Medicine University of Porto, Department of Pharmacology and Therapeutics, Porto, Portugal

⁷Hospital de São João, Department of Gastroenterology, Porto, Portugal

⁸Janssen-Cilag Polska Sp. z o.o., Warsaw, Poland

⁹Janssen-Cilag, Issy-les-Moulineaux, France

¹⁰Janssen-Cilag BV, Breda, The Netherlands

¹¹Janssen-Cilag Russia, EMEA Medical Affairs, Moscow, Russian Federation

¹²Janssen-Cilag S.p.A, Milan, Italy

¹³Janssen Global Services, LLC, Global Medical Affairs, Horsham, USA

¹⁴Azienda Ospedaliera Ordine Mauriziano – Presidio Umberto I, Gastroenterology Unit, Turin, Italy

¹⁵Clinical Center ISCARE, Clinical and Research Centre for Inflammatory Bowel Diseases, Prague, Czech Republic

¹⁶Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, IBD Unit, Rome, Italy

¹⁷Academic Medical Center, University of Amsterdam, Inflammatory Bowel Disease Centre, Amsterdam, The Netherlands

¹⁸Glasgow Royal Infirmary, Gastroenterology Unit, Glasgow, UK

¹⁹University Hospital of Nancy, University of Lorraine, INSERM Unité 954 and Department of Gastroenterology, Vandoeuvre les Nancy, France

Contact e-mail address: sdanese@hotmail.com

Introduction

Treat-to-target (T2T) has been proposed as an effective strategy to optimize management of Crohn’s disease (CD). STARDUST is a Phase IIIb randomized trial comparing a T2T maintenance strategy vs. standard of care (SoC) in CD patients (pts) treated with ustekinumab (UST). Here, we describe week (W) 48 endoscopic (primary endpoint) and clinical results.

Aims and methods: Adult pts with moderate–severely active CD (CD activity index (CDAI) 220–450) and Simple Endoscopic Score in CD (SES-CD) ≥3) who failed conventional therapy and/or one biologic were included. Pts received IV, weight-based UST ∼6mg/kg at W0 (baseline (BL)); then SC UST 90mg at W8. At W16, CDAI 70 responders were randomized (1:1) to the T2T or SoC treatment arms. Pts in the T2T arm were assigned to SC UST q12w or q8w based on 25% improvement in SES-CD score vs. BL. From W16 to W48, UST dose was further intensified up to q4w if the following targets were not met: CDAI <220 and ≥70-point improvement from BL, and C-reactive protein (CRP) ≤10 mg/L or faecal calprotectin (FCal) ≤250 µg/g. Pts who failed treatment target despite UST q4w were discontinued. In the SoC arm, UST dose was assigned by the investigator based on EU SmPC (q12w or q8w). Primary endpoint: endoscopic response at W48 (≥50% reduction in SES-CD score vs. BL on centrally read endoscopies). Non-responder imputation (NRI) and last observation carried forward (LOCF) were used for missing dichotomous and continuous variables, respectively. LOCF analysis was also a pre-planned sensitivity analysis for the primary endpoint. All p-values are nominal.

Results

In total, 500 pts were enrolled. At W16, 441 pts achieved a CDAI 70 response and were randomized to T2T (n = 220) or SoC (n = 221); 79.1% and 87.3%, respectively, completed W48. A numerically higher proportion of pts in the T2T vs. SoC arm achieved the primary endpoint at W48: 37.7% vs. 29.9% (p = 0.0933; NRI). A statistically significant difference was reached in a sensitivity analysis: 40.0% vs. 30.8% (p = 0.0494; LOCF). At W48, high rates of clinical response were achieved in the T2T and SoC arms: 68.2% vs. 77.8% (p = 0.0212; NRI)/89.5% vs. 89.6% (non-significant (NS); LOCF); clinical remission 61.4% vs. 69.7% (NS; NRI)/76.8% vs. 78.3% (NS; LOCF); improvement of ≥50% in FCal 39.4% vs. 46.5% (NS; NRI)/63.1% vs. 60.6% (NS; LOCF) and CRP 41.7% vs. 53.3% (p = 0.032; NRI)/53.2% vs. 57.2% levels (NS; LOCF). See the Table for other endpoints. In the T2T and SoC arms, 59.2% (122/206) and 53.2% (116/218) of pts started on UST q12w; of those, 59.8% (73/122) and 63.8% (74/116) were still on q12w at W48. Of pts who started on q8w, 40.5% (34/84) and 78.4% (80/102) remained on this regimen at W48 in T2T and SoC arms, respectively. At W48, 17% (35/206) of patients were on UST q4w in the T2T arm. No new safety signals were reported.

Conclusion

STARDUST is the first randomized T2T trial to use endoscopy at W16 to guide dose escalation in pts with CD. After 48W of maintenance therapy with UST, a numerically higher proportion of pts achieved the primary endpoint of endoscopic response in the T2T vs. SoC arm. T2T could be an additional tool for physicians to guide UST dosing decisions in CD. Overall, high clinical remission and biomarker responses with UST were achieved in both arms with UST at W48.

Abstract No: LB11.

Endpoint Data by Treatment Arm

	T2T arm ( N=220)			SoC arm ( N=221)			p-Valueb
Variable	Mean (95% CI) baselinea	Mean (95% CI) change from baseline at W16	Mean (95% CI) change from baseline at W48	Mean (95% CI) baselinea	Mean (95% CI) change from baseline at W16	Mean (95% CI) change from baseline at W48
SES-CD score	13.4(12.2, 14.6)N=220	–4.6(–5.5, –3.7)N=220	–5.0(–5.9, –4.0)N=220	12.7(11.7, 13.7)N=221	NA	–4.1(–4.9, –3.3)N=221	0.4856
CDAI score	287.2(279.9, 294.5)N=219	–178.0(–188.0, –168.0)N=219	–187.6(–198.4, –176.8)N=219	287.2(278.6, 295.8)N=221	–179.3(–189.7, –169.0)N=221	–187.1(–199.4, –174.8)N=221	0.9270
FCal, µg/g	1952.7(1461.4, 2443.9)N=197	–990.4(–1445.0, –535.8)N=197	1191.9(–1674.3, –709.6)N=197	1658.8(1304.9, 2012.7)N=189	–728.2(–1049.4, –407.0)N=189	–744.4(–1115.9, –372.8)N=189	0.1564
CRP, mg/L	16.405(13.233, 19.577)N=219	–7.704(–10.631, –4.777)N=219	–7.831(–10.844, –4.818)N=219	15.838(12.725, 18.952)N=219	–7.345(–9.684, –5.006)N=219	–7.909(–10.867, –4.950)N=219	0.9133

^aBaseline values for patients with at least one post-baseline assessment.

^bp-Values for changes at W48 are based on ANCOVA, with baseline value and stratification factors SES-CD score (≤16, >16) and prior exposure to biologics (none or 1) as covariates. Patients who had missing data at the designated analysis time point had their last value carried forward. Secondary endpoints included endoscopic remission (SES-CD score ≤2), clinical remission (CDAI <150 points), clinical response (CDAI <150 points or decrease from baseline of ≥100 points), change from baseline in biomarkers (FCal and CRP).

ANCOVA: analysis of covariance; CDAI: Crohn’s Disease Activity Index; CI: confidence interval; CRP: C-reactive protein; FCal: faecal calprotectin; SES-CD: Simple Endoscopic Score in Crohn’s Disease; SoC: standard of care; T2T: treat-to-target; NA: not assessed; W: week.

Disclosure: SD reports consultancy fees from AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ely Lilly, Enthera, Ferring Pharmaceuticals, Inc., Gilead, Hospira, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB, Inc., Vifor. SV received grants/research support from: MSD, AbbVie, Takeda, Janssen, Pfizer; received honoraria or consultation fees from AbbVie, MSD, Takeda, Ferring, Genentech/Roche, Shire, Pfizer, Inc., Galapagos, Mundipharma, Hospira, Celgene, Second Genome, Progenity, Lilly, Arena, GSK, Amgen, Ferring, Gilead, Janssen; and participated on speakers’ bureaus for AbbVie, MSD, Takeda, Ferring, Hospira, Pfizer, Janssen, Tillots. GRD’H has served as advisor for AbbVie, Ablynx, Allergan, Alphabiomics, Amakem, Amgen, AM Pharma, Applied Molecular Therapeutics; Arena Pharmaceuticals, AstraZeneca, Avaxia, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene/Receptos, Celltrion, Cosmo, DSM Pharma; Echo Pharmaceuticals, Eli Lilly, Engene, Exeliom Biosciences; Ferring, Dr Falk Pharma, Galapagos, Genentech/Roche, Gilead, GSK, GossamerBio, Hospira/Pfizer, Immunic, Johnson & Johnson, Kintai Therapeutics, Lycera, Medimetrics, Millennium/Takeda, Medtronics, Mitsubishi Pharma, MSD, Mundipharma, Nextbiotics, Novo Nordisk, Otsuka, Pfizer/Hospira, Photopill, ProciseDx, Prodigest, Prometheus Laboratories/Nestlé, Progenity, Protagonist, RedHill; Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Seres/Nestlé, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant, Vifor; received speaker fees from AbbVie, Biogen, Ferring, Johnson & Johnson, MSD, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Millennium/Takeda, Tillotts, Vifor. JP reports payment for lectures, including service on speakers’ bureaus, from Abbott, MSD, Roche, Pfizer, Janssen. AD reports fees for advisory board attendance from MSD, Abbvie, Takeda, Ferring, Dr Falk Pharma, Vifor, Pfizer, Janssen, Boehringer Ingelheim, Celgene, Roche, Tillots, Amgen, Fresenius Kabi; and honoraria for lectures and speakers’ bureaus from MSD, Abbvie, Takeda, Janssen, Ferring, Falk Foundation, Vifor, Roche, Tillotts, Pfizer, Immundiagnostik, Med Update GmbH. FM reports lecturing fees from Ferrring, OmPharma, MSD, AbbVie, Lab Vitoria, Vifor, Dr Falk, Takeda, Hospira, PharmaKern, Schering. MN is a full-time employee of Janssen-Cilag. MLB is a full-time employee of Janssen-Cilag and holds restricted stocks in Janssen-Cilag. ML is a full-time employee of Janssen-Cilag and holds restricted stocks in Janssen-Cilag. LN is a full-time employee of Janssen-Cilag. FL is a full-time employee of Janssen-Cilag. IB is a full-time employee of Janssen-Cilag. SS was an employee of Janssen Global Services at the time the study was conducted. MD reports personal fees from Janssen outside the submitted work. ML has no conflicts of interest to report. AA reports consulting fees from: AbbVie, Allergan, Amgen, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Ferring, Gilead, Janssen, Lilly, MSD, Mylan, Pfizer, Roche, Samsung Bioepis, Sandoz, Sofar, Takeda; lecture fees from: AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Chiesi, Ferring, Hospira, Janssen, MSD, Mitsubishi Tanabe, Nikkiso, Pfizer, Samsung Bioepis, Sandoz, Takeda, Tigenix; research grants from MSD, Takeda, Pfizer. ML has no conflicts of interest to report. DRG reports lecture fees from AbbVie, Janssen; and a travel grant from Takeda outside the submitted work. LP-B reports personal fees from AbbVie, Janssen, Genentech, Ferring, Tillots, Pharmacosmos,Celltrion, Takeda, Boerhinger Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestlé, Enterome, Allergan, MSD, Roche, Arena, Gilead,Hikma, Amgen, Bristol-Myers Sqibb, Vifor, Norgine, Mylan, Lilly, Fresenius, Oppilan Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera; research grants from AbbVie, MSD, Takeda outside the submitted work; and stock options in CTMA.

LB12 Intestinal ultrasound response and transmural healing after 48 weeks of treatment with ustekinumab in Crohn’s disease: STARDUST trial sub-study

T Kucharzik¹, R Wilkens^2,3, G Maconi⁴, M-A D’Agostino⁵, M Le Bars⁶, M Lahaye⁷, I Bravatà⁸, M Nazar⁹, L Ni¹⁰, E Ercole¹¹, M Allocca¹², N Machkova¹³, F de Voogd¹⁴, C Palmela¹⁵, R Vaughan¹⁶, C Maaser¹⁷

¹Klinikum Lüneburg, Klinik für Allgemeine Innere Medizin und Gastroenterologie, Lüneburg, Germany

²Hvidovre Hospital, Unit of Gastroenterology, Department of Medicine, Hvidovre, Denmark

³Bispebjerg Hospital, Digestive Disease Center, Copenhagen, Denmark

⁴Luigi Sacco University Hospital, Gastroenterology Unit Biomed and Clinical Sciences, Milan, Italy

⁵Ambroise Paré Hospital, APHP-Paris Saclay University, INSERM U1173, Laboratoire d’Excellence INFLAMEX, Rheumatology Department, Paris, France

⁶Janssen-Cilag, Issy les Moulineaux, France

⁷Janssen-Cilag B.V., Breda, The Netherlands

⁸Janssen-Cilag S.p.A., Milan, Italy

⁹Janssen-Cilag Polska Sp. z o.o., Warsaw, Poland

¹⁰Janssen-Cilag Russia, EMEA Medical Affairs, Moscow, Russian Federation

¹¹Azienda Ospedaliera Ordine Mauriziano – Presidio Umberto I, Gastroenterology Unit, Turin, Italy

¹²Humanitas University, Department of Gastroenterology, Milan, Italy

¹³Clinical Center ISCARE, Clinical and Research Center for Inflammatory Bowel Diseases, Prague, Czech Republic

¹⁴Amsterdam University Medical Center, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands

¹⁵Hospital Beatriz Ângelo, Division of Gastroenterology, Surgical Department, Loures, Portugal

¹⁶The Royal Melbourne Hospital, Department of Gastroenterology, Melbourne, Australia

¹⁷Klinikum Lüneburg, Ambulanzzentrum Gastroenterologie, Lüneburg, Germany

Contact e-mail address: torsten.kucharzik@klinikum-lueneburg.de

Introduction

STARDUST is a Phase IIIb randomized trial comparing treat-to-target (T2T) strategy vs. standard of care (SoC) in Crohn’s disease (CD) patients (pts) treated with ustekinumab (UST). We report week (W) 48 results from the intestinal ultrasound (IUS) STARDUST sub-study which assessed transmural healing in the ileum and colon.

Aims and methods: Pts (≥18 years) with moderate–severe active CD (CD Activity Index (CDAI) 220–450 and Simple Endoscopic Score for CD (SES-CD) ≥3) who failed conventional therapy and/or one biologic received weight-based IV UST dosing: ∼6 mg/kg at W0, then SC UST 90 mg at W8. At W16, pts with CDAI reduction ≥70 points were randomized (1:1) to T2T or SoC arms and received SC UST according to the protocol. Key IUS endpoints assessed at W4, W8, W16 and W48 were (central reading and IUS blinded to endoscopy): IUS response (≥25% bowel wall thickness (BWT) reduction from baseline (BL)); transmural healing (BWT normalization: ≤2.0 mm terminal ileum; ≤3.0 mm colon), colour Doppler imaging (CDI) signal ≤1; normal bowel wall echo-stratification (BWS); absence of inflammatory fat (i-Fat) overall and by ileum and colon. The most affected bowel segment at BL was used for all IUS parameters. We assessed agreement at BL (% pts) between IUS and endoscopy in defining the most affected part of the bowel. Reliability (kappa) between IUS response at different time points, and overall endoscopic response, clinical and biomarker outcomes at W48, were assessed.

Results

Of 77/88 pts enrolled in the IUS sub-study; n = 71 had BL and ≥1 post-BL IUS assessment. Overall IUS response and transmural healing rates at W48 were 46.3% and 24.1%, respectively. The most affected segments were the ileum in 65% and the colon in 35% of pts, with better outcomes found in the colon. The proportion of pts with normal IUS sub-scores increased progressively through W0, W16 and W48. At W48, normalization was more pronounced in the colon for BWT and CDI and similar between the ileum and colon for BWS and i-Fat (Table). At BL, agreement between IUS and endoscopy was very good in defining the most affected part of the bowel, particularly for the ileum 36/39 (92.3%), and good for specific overall bowel segment and specific colon segment (53/66 (80.3%) and 17/27 (63.0%), respectively). Fair/moderate reliability (kappa statistic range: 0.21–0.51) was observed between IUS response at different time points, and overall endoscopic response and FCal/complete biomarker outcomes at W48.

Conclusion

This was the first international, interventional, multi-centre study using IUS in CD. A clinically meaningful % of pts achieved progressive transmural healing up to W48, primarily in the colon. High agreement at BL between IUS and endoscopy in defining the most affected part of the bowel suggests that in addition to endoscopy, IUS could be of value in pts with ileal strictures and in detecting the most affected segment of the colon. Reliability between IUS response as early as W8, and endoscopic response and biomarker outcomes at W48, suggests IUS may be a useful tool in predicting later endoscopic response with UST in CD. This needs further exploration.

Abstract No: LB12.

IUS Response and Transmural Healing Over Time (IUS mITT Set) (Central Reading)

	Baseline			Week 16			Week 48
	Overall	Ileum	Colon	Overall	Ileum	Colon	Overall	Ileum	Colon
IUS response,a,b n/N (%)	–	–	–	24/67 (35.8)	14/43 (32.6)	10/24 (41.7)	25/54 (46.3)	15/38 (39.5)	10/16 (62.5)
IUS transmural healing,b,c n/N (%)	–	–	–	8/67 (11.9)	2/43 (4.7)	6/24 (25.0)	13/54 (24.1)	5/38 (13.2)	8/16 (50.0)
Components of IUS transmural healing over time
BWT normalization, n/N (%)	0/77 (0)d	0/50 (0)d	0/27 (0)d	10/67 (14.9)	2/43 (4.7)	8/24 (33.3)	14/54 (25.9)	6/38 (15.8)	8/16 (50.0)
Normal vascularization (CDI signal 0 or 1), n/N (%)	28/75 (37.3)	18/49 (36.7)	10/26 (38.5)	38/62 (61.3)	23/42 (54.8)	15/20 (75.0)	37/51 (72.5)	25/37 (67.6)	12/14 (85.7)
Normal BWS, n/N (%)	28/76 (36.8)	22/49 (44.9)	6/27 (22.2)	36/66 (54.5)	26/43 (60.5)	10/23 (43.5)	34/53 (64.2)	24/38 (63.2)	10/15 (66.7)
Normal i-Fat, n/N (%)	19/76 (25.0)	11/49 (22.4)	8/27 (29.6)	30/67 (44.8)	20/43 (46.5)	10/24 (41.7)	30/54 (55.6)	19/38 (50.0)	11/16 (68.8)

The mITT analysis set included randomized pts with most affected part of the bowel data available. If three out of the four IUS parameters are normalized and the fourth is ‘not assessed/not assessable’, IUS remission is considered positive.

^aIUS response is defined as a reduction of ≥25% from BL in BWT.

^bTo determine IUS response and transmural healing, the most affected (most thickened) part of the bowel wall was used.

^cIUS transmural healing is defined as normalization of BWT, vascularization (colour Doppler signal), echo-stratification and inflammatory mesenteric fat.

^dAt BL, only pathological BWT was required.

BL: baseline; BWS: bowel wall stratification; BWT: bowel wall thickness; CDI: colour Doppler imaging; i-Fat: inflammatory mesenteric fat; IUS: intestinal ultrasound; (m)ITT: (modified) intention-to-treat.

Disclosure: TK reports financial support for study design and for central reading from Janssen during the conduct of the study; and honoraria for advisory boards and lectures from Janssen outside the submitted work. RW reports personal fees from Janssen-Cilag during the conduct of the study; and travel grants and speaker fees from Takeda Denmark and AbbVie Denmark outside the submitted work. GM reports fees for advisory board participation from AbbVie, Janssen-Cilag, Roche; and speaker fees from Alfa Sigma. MAD’A has no conflicts of interest to report. MLB is a full-time employee of Janssen-Cilag and holds restricted stocks in Janssen-Cilag. ML is a full-time employee of Janssen-Cilag and holds restricted stocks in Janssen-Cilag. IB is a full-time employee of Janssen-Cilag. MN is a full-time employee of Janssen-Cilag. LN is a full-time employee of Janssen-Cilag. EE has no conflicts of interest to report. MA reports consulting fees from Nikkiso Europe; and lecture fees from Janssen and Pfizer outside the submitted work. NM reports lecture fees from AbbVie s.r.o., Pfizer PFE s.r.o., Takeda Pharmaceuticals s.r.o and Janssen-Cilag s.r.o outside the submitted work. FAEdV received speaker and honoraria fees from Janssen. CP has no conflicts of interest to report. RV has no conflicts of interest to report. CM reports personal fees from AbbVie, MSD, Falk Foundation, Ferring, Takeda, Janssen, Celgene, Vifor Pharma outside the submitted work.

LB13 MicroRNAs of extracellular vehicles from pancreatic juice as biomarkers for early detection of pancreatic cancer

K Nesteruk, IJM Levink, E De Vries, I Visser, MP Peppelenbosch, DL Cahen, MJ Bruno, GM Fuhler

Erasmus University Medical Center, Gastroenterology and Hepatology, Amsterdam, The Netherlands

Contact e-mail address: kv.nesteruk@gmail.com

Introduction

Patients with resectable pancreatic cancer (PC) survive longer than patients at an advanced stage.¹ However, early detection is challenging due to the late presentation of symptoms and limited visibility of sub-centimeter cancers on imaging. A novel approach is to support clinical diagnosis with molecular markers. MicroRNA derived from extracellular vehicles (EVs) in blood initially seemed a promising tool, but did not reach clinical applicability due to limited diagnostic value. In contrast, pancreatic juice (PJ), which is in close contact with ductal cells from which PC arises, is a potentially more viable biomarker source. Thus, the aim of our study was to evaluate the performance of PJ-derived miRNA for detection of PC.

Aims and methods: PJ was collected from the duodenum during EUS after secretin stimulation from 148 patients: 41 patients with PC, 94 individuals under surveillance for hereditary predisposition (n = 50) or IPMN (n = 44; 20 with or 24 without worrisome features) and eight patients with pancreatitis. EVs were isolated from PJ supernatant, and their size and concentration were analyzed (NTA). The microRNAs miR-16, miR-21, miR-25, miR-155 and miR-210 were selected based on literature and analyzed by qPCR. Concentration of PLA2G1B was evaluated by ELISA and total protein concentration by Lowry assay. For statistical analysis, either a Mann–Whitney U-test or a Wilcoxon signed rank test was performed. ROC curves and AUC were used to assess the sensitivity and specificity of miRNA expression.

Results

When comparing PC to the non-cancer group, PJ quality was comparable, as confirmed by concentrations of PLA2G1B (p = 0.10) and total protein (p = 0.10). Interestingly, EVs of PJ from patients with PC were larger (p = 0.004), while there was no difference in their concentration (p = 0.28) and microRNA expression (miR-16 p = 0.17; miR-21 p = 0.09; miR-25 p = 0.50; miR-155 p = 0.13, miR-210 p = 0.11). In subgroup analysis, significantly larger EVs were detected in patients with PC in comparison with the hereditary control group (p<0.05), with no difference in particle concentration (p = 0.83). The miR-21 expression was higher in pancreatitis (p<0.05) and PC (p<0.05) than in individuals with hereditary predisposition. The miR-210 expression was increased in PC (p<0.05) and IPMN with worrisome features (p<0.05), as compared to individuals with hereditary predisposition. The area under the curve for the detection of PC by a combination of miR-21, miR-210 and EV size was 0.68 (specificity 81.6%, sensitivity 47.5%).

Conclusion

Detection of miRNA from EVs in PJ is feasible. The combination of miR-21, miR-210 and EV size may be a useful diagnostic biomarker set for early detection of PC.

Disclosure: Nothing to disclose.

Reference

1. Pereira SP, et al. Early detection of pancreatic cancer. Lancet Gastroenterol Hepatol 2020; 5: 698–710.

LB14 Innervated pancreas organoids as an improved ex vivo model to study pancreatic neuropathy and pancreatic cancer

HE Besikcioglu¹, Ü Yurteri¹, H Friess², R Istvanffy¹, IE Demir¹

¹Technical University of Munich, Department of Surgery, Klinikum rechts der Isar, Munich, Germany

²Klinikum rechts der Isar, Department of Surgery, Munich, Germany

Contact e-mail address: erdincbesikcioglu@gmail.com

Introduction

Pancreatic cancer is characterized by a bi-directional interaction between neurons and several types of non-neural pancreatic cells, and by profound plasticity of the intra- and extrapancreatic nerve supply. The absence of neural cells in current pancreatic organoid models cause limitations to investigate these interactions.

Aims and methods: We generated “innervated pancreas organoids” with the intention to generate improved ex vivo models for studying and pancreatic neuropathy. For this purpose, we isolated pancreas organoids from wild type (WT) and Kras^+/LSLG12DTrp53^fl/flp48^+/Cre (KPC) mice and co-cultured them with human induced pluripotent stem cells (hiPSCs) derived neural crest cells as embryonic progenitors of the peripheral nervous system. Neuronal morphology was observed on the third day of co-culture. We terminated the co-cultivation on the seventh day and performed wholemount IF staining with anti-E-cadherin, anti-βIII-Tubulin and anti-GFAP antibodies and imaged via confocal microscopy.

Results

βIII-Tubulin positive neurons were observed both in WT+NCCs and KPC+NCCs cultures, but we did not observe GFAP positivity. In the neuronal morphometry, neuronal projection lengths did not differ between the KPC+NCCs and WT+NCCs groups. However, we observed increased branching in the KPC+NCCs group (p = 0.0012). In addition, neurons were observed even inside the organoids in KPC+NCCs group, while located just around the organoids in WT+NCCs group. We also compared the organoid perimeters between mono-cultures and co-cultures, but NCCs do not have significant effect on organoid size.

Conclusion

We show that neurons derived from the neural crest can lead to exhibit innervation of the pancreas organoids and result in modulation of the neuro-exocrine cell interaction in the pancreatic cancer microenvironment. Further functional implications of such innervated organoids will be the subject of our upcoming investigations.

Disclosure: Nothing to disclose.

LB15 Effect of intra-pancreatic glial cell depletion on tumour progression and pain perception in pancreatic cancer

Ü Yurteri¹, HE Besikcioglu¹, R Istvanffy¹, GO Ceyhan², H Friess¹, IE Demir³

¹Technical University of Munich, Department of Surgery, Klinikum rechts der Isar, Munich, Germany

²Acibadem University, HPB Unit, Department of General Surgery, Ataşehir/Istanbul, Turkey

³Klinikum Rechts Der Isar, Technical University of Munich, Department of Surgery, Munich, Germany

Contact e-mail address: gulsumyurteri@gmail.com

Introduction

It has been shown that Schwann cell activation induces pain suppression and causes a delay of pain perception at a very early stage of pancreatic Ductal adenocarcinoma (PDAC) progression. However, the role of peripheral glial cells in the development and progression of PDAC is still unexplored.

Aims and methods: In order to investigate the potential role of glial cells in pancreatic carcinogenesis and progression, we interbred KC mice (Ptf1a-cre; LSL-KrasG12D) with GFAP-Tk mice, in which selective depletion of activated glial cells can be induced upon ganciclovir administration. We analysed pain behaviour and intensity in these mice via von-Frey filaments and PanIN (pancreatic intraepithelial neoplasia) progression. In addition, we performed a thorough characterization of the tumour microenvironment by performing immune-labelling (IHC) for quantifying GFAP⁺ (glial fibrillary acidic protein) cells, angiogenesis (CD31), neurogenesis (S100), stromal activation (a-SMA and collagen) and tumour infiltration by immune cells (CD45, CD8 and F4/80). To understand the role of glial cells on the activation of primary and secondary nociceptive neurons, and on astroglia and microglia, we performed IHC on spinal cord sections of mice, and stainings were done against c-Fos, p-Erk, GFAP, p75, p38/38 and Iba-1 antibodies.

Results

According to von Frey test results, we observed decreased pain intensity when the glial cells were depleted. IHC results showed that the relative PanIN lesion density was higher when glial cell number was high (p<0.0001). Furthermore, in glial cell-depleted mice, we detected a lower vascular density (p<0.001) and neural density (p = 0.0003), a lower myofibroblast density (p = 0.003), leukocyte density (p = 0.003), cytotoxic T-cell density (p = 0.001) and fewer macrophages. Finally, in glial cell-depleted mice, the spinal cord of the thoracic region exhibited lower concentrations of c-Fos (p<0.001), p-Erk (p<0.001), astroglial markers (p<0.001) and microglial markers (p<0.001).

Conclusion

Glial cells have a major role in in PDAC progression, in pain perception, angiogenesis, neural density, activation of stroma, tumour infiltration, and additionally in the co-activation of spinal astroglia and microglia in this genetically engineered mouse model. Further studies are needed for understanding the molecular and cellular mechanisms behind glia-cell-maintained tumour progression in PDAC.

Disclosure: Nothing to disclose.

LB16 Determining which novel biomarkers are ready for evaluation for use in early detection of lower gastrointestinal cancers in low-prevalence populations: A systematic review

P Druce¹, N Calanzani², C Snudden², K Milley¹, R Boscott², D Behiyat², J Martinez Gutierrez¹, S Saji², J Oberoi¹, G Funston², M Messenger³, J Emery¹, F Walter²

¹The University of Melbourne, Centre for Cancer Research and Department of General Practice, Melbourne, Australia

²University of Cambridge, Department of Public Health and Primary Care, Cambridge, UK

³University of Leeds, Faculty of Medicine and Health, School of Medicine, Leeds, UK

Contact e-mail address: paige.druce@unimelb.edu.au

Introduction

Lower gastrointestinal (GI) cancers are a major cause of cancer deaths worldwide. Prognosis improves with earlier diagnosis, and non-invasive biomarkers have the potential to aid with early detection. Substantial investment has been made into the development of biomarkers, however studies are often carried out in specialist settings and few have been evaluated for implementation in low-prevalence populations.

Aims and methods: This review aimed to identify novel biomarkers for the detection of lower GI cancers that have the potential to be developed for use in primary care. MEDLINE, Embase, Emcare and Web of Science were searched for studies published in English from January 2000 to October 2019. Screening was completed independently by two reviewers. Guided by the CanTest Framework (a novel translational pathway for diagnostic tests), we searched for biomarkers (either individual or in panels) with validated measures of diagnostic performance (beyond the discovery phase) used to detect colorectal and anal cancers. All study designs and health-care settings were included, but studies with fewer than 50 cases/controls were excluded. Non-invasive biomarker sample sources feasible for use in the community setting were included (i.e. blood, urine, faeces, saliva and breath). Diagnostic performance measures (such as sensitivity, specificity and area under the curve) were examined. Narrative synthesis was used to describe the results, and where possible measures of specificity and sensitivity were meta-analysed using a random effects bivariate binomial model.

Results

A total of 142 studies reporting on biomarkers for lower GI cancers were identified, for 24,844 colorectal cancer cases and 45,004 controls (most often healthy, 31.5% had adenomas/polyps or non-malignant conditions). Studies were most commonly conducted in China (n = 62), and the most common setting was a hospital (n = 96). A total of 378 unique biomarkers were identified (126 microRNAs/other RNAs, 86 proteins, 45 DNA markers, 44 autoantibodies/other immunological markers, 42 metabolic markers, 15 DNA methylation markers, 4 circulating tumour DNA and 16 other). More than a third of biomarkers (n = 54) were reported on in more than one study, with 35 of these markers having individual measures of performance provided. Heterogeneity of study design, population type, and sample source precluded meta-analysis for all markers, except for two of the most commonly reported novel biomarkers: methylated septin 9 (mSEPT9) and pyruvate kinase type tumour M2 (TuM2-PK). The estimated sensitivity and specificity of mSEPT9 was 80.6% (95% CI 76.6–84.0%) and 88.0% (95% CI 79.1–93.4%), respectively, whilst TuM2-PK had an estimated sensitivity of 81.6% (95% CI 75.2–86.6%) and specificity of 80.1% (95% CI 76.7–83.0%).

Conclusion

There is a large amount of literature describing novel biomarkers for lower GI cancers, with much heterogeneity across studies. Two novel biomarkers (mSEPT9 and TuM2-PK) emerged from the literature with potential for further development for use in lower prevalence populations. Both presented with high sensitivity and specificity in specialist populations, but further research is needed to validate and implement these biomarkers to support the early detection of lower GI cancers in primary care.

Disclosure: Nothing to disclose.

LB17 Cost-effectiveness of colorectal cancer surveillance in Hodgkin lymphoma survivors

BLM Ykema¹, A Gini², LS Rigter¹, MCW Spaander³, LMG Moons⁴, TM Bisseling⁵, BMP Aleman⁶, GA Meijer⁷, FE van Leeuwen⁸, P Snaebjornsson⁷, B Carvalho⁷, ME van Leerdam^1,9, I Lansdorp-Vogelaar², DICHOS Study Group

¹Netherlands Cancer Institute, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands

²Erasmus Medical Center, Department of Public Health, Rotterdam, The Netherlands

³Erasmus Medical Center Rotterdam, Gastroenterology and Hepatology, Rotterdam, The Netherlands

⁴University Medical Center Utrecht, Gastroenterology and Hepatology, Utrecht, The Netherlands

⁵Radboud University Medical Centre, Department of Gastroenterology and Hepatology, Nijmegen, The Netherlands

⁶Netherlands Cancer Institute, Department of Radiation Oncology, Amsterdam, The Netherlands

⁷Netherlands Cancer Institute, Department of Pathology, Amsterdam, The Netherlands

⁸Netherlands Cancer Institute, Department of Epidemiology, Amsterdam, The Netherlands

⁹Leiden University Medical Center, Department of Gastroenterology and Hepatology, Leiden, The Netherlands

Contact e-mail address: b.ykema@nki.nl

Introduction

Hodgkin lymphoma (HL) survivors treated with abdominal radiotherapy (ART) and/or procarbazine have an increased risk of developing colorectal cancer (CRC).¹ We investigated the cost-effectiveness of CRC surveillance in HL survivors. Also, we investigated whether intensified surveillance compared with the Dutch CRC population-based screening would be advisable in HL survivors.

Aims and methods: We adjusted the well-established and validated Microsimulation Screening Analysis-Colon model² to reflect the higher risk for developing CRC and the higher other-cause mortality risk in HL survivors. Ninety CRC surveillance strategies were evaluated varying starting and stopping age, interval, and modality (colonoscopy, fecal immunochemical test (FIT, OC-Sensor; cut-offs: 10, 20, or 47 µg Hb/g feces), and multi-target stool DNA test (Cologuard^®)).^3,4 Analysis was also stratified per primary treatment (the entire cohort, HL survivors treated with ART and procarbazine or procarbazine without ART). CRC deaths averted (compared to no surveillance) and incremental cost-effectiveness ratios (ICERs) were primary outcomes. The optimal surveillance strategy was identified assuming a willingness-to-pay threshold of $20,000 per life-year gained (LYG). Several sensitivity analyses were performed to reinforce the results under a variety of assumptions, including a higher all-cause mortality, a lower CRC relative survival, and higher costs for CRC treatment and care.

Results

In the entire cohort, 51 deaths per 1000 HL survivors were predicted in the absence of surveillance. The optimal surveillance strategy was annual FIT (47 µg Hb/g feces) from age 40 to 70 years, which might avert 73% of CRC deaths in HL survivors (compared to no surveillance; ICER: €17,000/LYG). For HL survivors treated with procarbazine without ART and with ART and procarbazine, the predicted deaths in absence of surveillance were 36 and 68 per 1000 HL survivors, respectively. The optimal surveillance strategy in HL survivors treated with procarbazine without ART was annual FIT (47 µg Hb/g feces) from age 45 to 70 years (CRC mortality averted 69%; ICER: €13,000/LYG), and when treated with ART and procarbazine annual FIT at a lower cut-off level (20 µg Hb/g feces) surveillance from age 40 to 70 years was most cost-effective (CRC mortality averted 77%; ICER: €10,000/LYG). Results were robust under several sensitivity analyses with no changes compared to base case (annual FIT surveillance) or impacts mainly on the optimal FIT positivity cut-off.

Conclusion

CRC surveillance in HL survivors is cost-effective and should commence earlier than screening occurs in the general population. For all HL subgroups, FIT surveillance was the most cost-effective strategy.

Disclosure: Nothing to disclose.

References

1. Van Eggermond AM, Schaapveld M, Janus CP, et al. Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors. Br J Cancer 2017; 117: 306–314.

2. Gini A, Meester RGS, Keshavarz H, et al. Cost-effectiveness of colonoscopy-based colorectal cancer screening in childhood cancer survivors. J Natl Cancer Inst 2019; 111: 1161–1169.

3. Rigter LS, Spaander MCW, Aleman BMP, et al. High prevalence of advanced colorectal neoplasia and serrated polyposis syndrome in Hodgkin lymphoma survivors. Cancer 2019; 125: 990–999.

4. Ykema B, Rigter L, Spaander M, et al. Diagnostic accuracy of stool tests for colorectal cancer surveillance in Hodgkin lymphoma survivors. J Clin Med 2020; 9: 190.

LB18 Etrolizumab versus placebo in tumor necrosis factor antagonist naive patients with ulcerative colitis: Results from the randomized Phase III LAUREL trial

S Vermeire¹, PL Lakatos², T Ritter³, S Hanauer⁴, B Bressler⁵, R Khanna⁶, K Isaacs⁷, S Shah⁸, AK Kadva⁹, H Tyrrell¹⁰, YS Oh⁹, S Tole⁹, A Chai⁹, J Pulley¹⁰, W Zhang⁹, BG Feagan⁶, on behalf of the LAUREL Study Group; Drs. Vermeire and Lakatos contributed equally to this work

¹University Hospital Leuven, Leuven, Belgium

²McGill University, Montreal, Canada

³GI Alliance, Southlake, USA

⁴Northwestern University, Chicago, USA

⁵St. Paul’s Hospital, Vancouver, Canada

⁶Western University, London, Canada

⁷University of North Carolina School of Medicine, Chapel Hill, USA

⁸Gujarat Hospital, Gastro and Vascular Center, Gujarat, India

⁹Genentech, Inc., South San Francisco, USA

¹⁰Roche Products Limited, Welwyn Garden City, UK

Contact e-mail address: severine.vermeire@uz.kuleuven.ac.be

Introduction

Etrolizumab, an anti-β7 monoclonal antibody, binds α4β7 and αEβ7 integrins to inhibit both trafficking of immune cells into the gut and their inflammatory effects on the gut lining. We evaluated the safety, efficacy, and tolerability of etrolizumab in moderately to severely active ulcerative colitis (UC) patients who were naive to tumor necrosis factor (TNF) antagonists.

Aims and methods: LAUREL (NCT02165215) was a multicenter, randomized, double-blind, parallel-group, placebo-controlled Phase III study of etrolizumab in TNF antagonist-naive patients with moderately to severely active UC. In the induction phase, patients received subcutaneous, open-label etrolizumab (105 mg every four weeks). Patients with a clinical response at week 10 were randomly assigned 1:1 at week 12 to etrolizumab 105 mg or placebo (PBO), administered every four weeks for a total of 52 weeks in the maintenance phase. The primary efficacy endpoint was remission (Mayo Clinic total score (MCS) ≤2, with individual subscores ≤1 and a rectal bleeding subscore (RBS) of 0) at week 62 among patients with a clinical response (MCS with ≥3-point decrease and 30% reduction from baseline and ≥1-point decrease in RBS or an RBS of 0 or 1) at week 10.

Results

The study enrolled 359 patients. Of 347 patients who completed the induction phase to week 10, 214 clinical responders were randomly assigned to receive either PBO (n = 106) or etrolizumab (n = 108) in the maintenance phase. Eighty (74.1%) etrolizumab patients and 42 (39.6%) placebo patients completed week 62. Treatment arms had similar baseline characteristics: median age was 36–38 years, median disease duration was 5–6 years, and median MCS was 8–9. At week 62, the remission rate observed in patients assigned to etrolizumab was not significantly different from PBO (29.6% vs. 20.6%, respectively; treatment difference 7.7% (95% CI –4.2, 19.2); p = 0.1942; Table). Endoscopic improvement at week 62 was achieved in 38.0% of etrolizumab patients vs. 22.5% of PBO patients (nominal p = 0.0235). Corticosteroid (CS)-free remission at week 62 among patients who received baseline CS was achieved in 18.2% of etrolizumab patients vs. 8.0% of PBO patients (nominal p = 0.1415). At week 62, histologic remission was achieved in 42.4% of etrolizumab patients and 21.8% of PBO patients (nominal p = 0.0075). Endoscopic remission at week 62 was achieved in 30.6% of etrolizumab patients and 16.7% of PBO patients (nominal p = 0.0293). Most adverse events were nonserious and grades 1/2. No deaths or cases of progressive multifocal leukoencephalopathy were observed.

Abstract No: LB18.

Results of Primary and Key Secondary Efficacy Endpoints During Maintenance (Week 62) Treatment with Etrolizumab and PBO

	PBO N=102a	Etrolizumab N=108a	Treatment difference (95% CI)	p-Value
Remission, n (%)	21 (20.6)	32 (29.6)	7.7% (–4.2, 19.2)	0.1942
Endoscopic improvement,,b n (%)	23 (22.5)	41 (38.0)	14.4% (1.8, 26.3)	0.0235c
CS-free remission in patients receiving baseline CS,d n/N (%)	4/50 (8.0)	10/55 (18.2)	9.9% (–4.5, 23.1)	0.1415c
Histologic remission,e n/N (%)	17/78 (21.8)	36/85 (42.4)	19.8% (5.2, 33.1)	0.0075c
Endoscopic remission,f n (%)	17 (16.7)	33 (30.6)	12.8% (1.1, 23.9)	0.0293c

^aPopulation is the modified intention-to-treat population (patients who were randomized and dosed in maintenance).

^bMayo Clinic endoscopic subscore ≤1.

^cSince the primary endpoint was not met, no key secondary endpoints were formally tested. Nominal p-values are shown here.

^dIn patients receiving baseline CS, remission with no CS use for 24 weeks before week 62.

^eNancy histological index (NHI) ≤1.

^fMayo Clinic endoscopic subscore=0; p-values are used for secondary endpoints as the primary endpoint was not met.

CI, confidence interval; CS, corticosteroid; PBO, placebo.

Conclusion

Despite nominally statistically significant benefits with etrolizumab vs. placebo in endoscopic improvement, endoscopic remission, and histologic remission, in this cohort of TNF-naive patients the primary endpoint of remission at week 62 among week 10 responders was not met. No new or unexpected safety signals occurred, and most adverse events were low grade.

Disclosure: SV reports grants from Pfizer, AbbVie, Takeda, Johnson & Johnson; other from AbbVie, Arena Pharmaceuticals, Avaxia, Boehringer Ingelheim, Celgene, Dr. Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, Hospira, Janssen, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Takeda, Theravance, Tillots Pharma AG. PL reports personal fees from AbbVie, Arena Pharmaceuticals, Genentech, Janssen, Merck, Pfizer, Takeda. TR reports other from Roche/Genentech; personal fees from Roche/Genentech during the conduct of the study; personal fees from AbbVie, Arena, Boehringer-lngelheim, Ferring, Rebiotix, Gilead, Intercept, Janssen, Eli Lilly, from Pfizer, Prometheus, Takeda outside the submitted work. SH reports consultant fees from AbbVie, Allergan, Amgen, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Genentech, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Nestle, Novartis, Pfizer, Progenity, Receptos, Saliz, Samsung Bioepis, Seres Therapeutics, Takeda, Tigenix, UCB Pharma, VHsquared. JP reports employment with Roche. WZ reports employment with Genentech, Inc. BB, KI, and SS have nothing to disclose. RK reports personal fees from AbbVie, Janssen, Takeda, Innomar, Robarts Clinical Trials, Merck, Pfizer, Pendopharm, Encyte, as well as personal fees and other from Roche. AK is an employee of Genentech, a member of Roche, and a Roche options shareholder. HT is a Roche Employee and stockholder. YO reports he is an employee of Roche, the company sponsoring the study, and that he owns Roche stock as part of his compensation. ST is a Genentech employee and Roche stockholder. AC reports that she is an employee of Genentech, a member of the Roche Group, and that she owns Roche stock as an employee. BF reports personal fees from Ablynx, Actogenix, AdMIRx, Inc., Akebia Therapeutics, Allergan, Avaxia Biologics, Inc., Avir Pharma, Atlantic Pharma, Baxter Healthcare Corporations, Biogen Idec, BioMx Israel, Boehringer-Ingelheim, Boston Pharmaceuticals, Calpyso Biotech, Celgene, Elan/Biogen, EnGene, Ferring, Galapagos, Genentech/Roche, GiCare Pharma, Gilead, Given Imaging, GlaxoSmithKline, Gossamer Pharma, Inception IBD, Inc., Ironwood, Japan Tobacco Company, Kyowa Kakko Kirin Co Ltd, Lexicon, Eli Lilly, Lycera Biotech, Merck, Mesoblast Pharma, Millennium, Nestle, NextBiotix, Novo Nordisk, Novartis, ParImmune, Progenity, Prometheus Therapeutics & Diagnostics, Protagonist, Qu Biologics, Roche, Shire, Sienna Biologics, Sigmoid Pharma, Synergy Pharma, Teva Pharma, TiGenix, Tillotts, UCB, Vertex, VHsquare, Vivelix Pharma, Wyeth Zealand, Zyngenia; and grants and personal fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen Biotech/Centocor, Johnson & Johnson/Janssen, Pfizer, Takeda.

LB19 Efficacy and safety of filgotinib as maintenance therapy for patients with moderately to severely active ulcerative colitis: Results from the Phase IIB/III SELECTION study

L Peyrin-Biroulet¹, EV Loftus Jr ², S Danese³, S Vermeire⁴, WJ Sandborn⁵, R Fogel⁶, S Nijhawan⁷, R Kempinski⁸, R Filip⁹, I Hospodarskyy¹⁰, J McNally¹¹, C Yun¹¹, S Zhao¹¹, X Liu¹¹, C Tasset¹², R Besuyen¹³, M Watanabe¹⁴, S Schreiber¹⁵, G Rogler¹⁶, T Hibi¹⁷, BG Feagan¹⁸

¹Lorraine University, Nancy University Hospital and Inserm U1256 NGERE, Vandoeuvre les Nancy, France

²Mayo Clinic College of Medicine, Rochester, USA

³Humanitas University, Milan, Italy

⁴University Hospitals Leuven, Leuven, Belgium

⁵University of California San Diego, La Jolla, USA

⁶Clinical Research Institute of Michigan, Detroit, USA

⁷SMS Medical College and Hospital, Jaipur, India

⁸CM Oporów, Wrocław, POLAND

⁹Clinical Hospital No. 2, Rzeszów, Poland

¹⁰Ternopil National Medical University, Voli, Ukraine

¹¹Gilead Sciences, Inc., Foster City, USA

¹²Galapagos NV, Mechelen, Belgium

¹³Galapagos BV, Leiden, The Netherlands

¹⁴Tokyo Medical and Dental University, Tokyo, Japan

¹⁵University Hospital Schleswig-Holstein, Department of Medicine I and Institute for Clinical Molecular Biology, Kiel, Germany

¹⁶University Hospital of Zurich, University of Zurich, Zurich, Switzerland

¹⁷Kitasato University Kitasato Institute Hospital, Center for Advanced IBD Research and Treatment, Tokyo, Japan

¹⁸Western University, London, Canada

Contact e-mail address: peyrinbiroulet@gmail.com

Introduction

Filgotinib (FIL) is a Janus kinase 1 inhibitor being investigated for several inflammatory conditions, including ulcerative colitis (UC).

Aims and methods: The SELECTION (NCT02914522) Maintenance Study is a double-blind, randomized trial of FIL as maintenance therapy for patients with moderately to severely active UC who achieved clinical remission or Mayo Clinic score (MCS) response after 10 weeks of induction with FIL 200 mg, FIL 100 mg, or placebo (PBO). Patients randomized to FIL induction were rerandomized 2:1 to their induction FIL dose or PBO. Patients randomized to PBO during induction continued PBO maintenance. Mandatory steroid tapering was required. Primary endpoint was endoscopic/rectal bleeding/stool frequency (EBS) remission at wk 58, defined by Mayo endoscopic subscore (ES) ≤1, rectal bleeding subscore = 0, and ≥1-pt decrease in stool frequency subscore (SFS) from baseline and SFS ≤1. Key secondary endpoints included six-month corticosteroid-free clinical remission, sustained clinical remission, MCS remission, endoscopic remission, and Geboes histologic remission at wk 58.

Results

A total of 664 patients were enrolled and treated in the Maintenance Study (n = 93, 270, and 301 from induction PBO, FIL 100 mg and FIL 200 mg arms, respectively); efficacy analyses included only patients who received FIL during induction (n = 558). Baseline demographics and disease characteristics were generally balanced across treatment arms; approx. 40% of patients were biologic experienced. A significantly higher proportion of patients on FIL 200 mg or FIL 100 mg achieved EBS remission vs. PBO (Table). Significantly higher proportions of patients achieved key secondary endpoints, including six-month corticosteroid-free clinical remission and histologic remission with FIL 200 mg vs. PBO. Overall, the incidences of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar across treatment arms (Table). Serious infection and herpes zoster infection were infrequent across groups. No opportunistic infections occurred. There were no venous thromboses, including pulmonary embolism, among FIL-treated patients. Two patients on FIL 200 mg died (one from asthma exacerbation, one from left ventricular failure), both considered unrelated to FIL.

Conclusion

FIL 200 mg and 100 mg were effective as maintenance treatment for patients with moderately to severely active UC who had achieved clinical response to induction treatment with FIL. FIL 200 mg met all key secondary endpoints, including endoscopic, histologic, and six-month corticosteroid-free remission. FIL was well tolerated in patients with moderate to severely active UC.

Abstract No: LB19.

SELECTION Maintenance Study Summary of Efficacy and Safety

Induction treatment		FIL 200 mg		FIL100 mg
Maintenance treatment		PBO	FIL 200mg	PBO	FIL 100 mg
EBS remission, n/N (%)		11/98 (11.2)	74/199 (37.2)*	12/89 (13.5)	41/172 (23.8)†
6-month corticosteroid-free clinical remission, n/N (%)		3/47 (6.4)	25/92 (27.2)*	2/37 (5.4)	11/81 (13.6)
Sustained clinical remission, n/N (%)		5/98 (5.1)	36/199 (18.1)*	7/89 (7.9)	15/172 (8.7)
MCS remission, n/N (%)		9/98 (9.2)	69/199 (34.7)*	12/89 (13.5)	39/172 (22.7)
Endoscopic remission, n/N (%)		6/98 (6.1)	31/199 (15.6)*	7/89 (7.9)	23/172 (13.4)
Geboes histologic remission, n/N (%)		13/98 (13.3)	76/199 (38.2)*	16/89 (18.0)	48/172 (27.9)
Induction treatment	PBO	FIL 200 mg		FIL 100 mg
Maintenance treatment	PBO (n=93)	PBO (n=99)	FIL 200 mg (N=202)	PBO (N=91)	FIL 100 mg (N=179)
AE, n (%)	57 (61.3)	59 (59.6)	135 (66.8)	60 (65.9)	108 (60.3)
Discontinued due to AE, n (%)	3 (3.2)	2 (2.0)	7 (3.5)	4 (4.4)	10 (5.6)
Serious AE, n (%)	4 (4.3)	0	9 (4.5)	7 (7.7)	8 (4.5)
Death, n (%)	0	0	2 (1.0)	0	0
Infections, n (%)	21 (22.6)	25 (25.3)	71 (35.1)	27 (29.7)	46 (25.7)
Serious infections, n (%)	1 (1.1)	0	2 (1.0)	2 (2.2)	3 (1.7)
Herpes zoster, n (%)	0	0	1 (0.5)	1 (1.1)	0
Any venous thrombosis, n (%)	2 (2.2)	0	0	0	0
Any arterial thrombosis, n (%)	0	0	0	0	1 (0.6)

EBS remission=ES of 0 or 1, rectal bleeding subscore of 0, and ≥1-point decrease in SFS from baseline to achieve a SFS of 0 or 1; six-month corticosteroid-free EBS remission=EBS remission with no corticosteroid use for the indication of UC for ≥6 months prior to wk 58 among patients who were on corticosteroids at baseline of maintenance study; sustained EBS remission=EBS remission at both wk 10 and wk 58; MCS remission=MCS of ≤2 and no single subscore >1; endoscopic remission=ES of 0. Geboes histologic remission=Grade 0 of ≤0.3, Grade 1 of ≤1.1, Grade 2a of ≤2A.3, Grade 2b of 2B.0, Grade 3 of 3.0, Grade 4 of 4.0, and Grade 5 of 5.0.

*p<0.025; †p<0.05 FIL dose arm vs. PBO.

AE: adverse event; FIL: filgotinib; MCS: Mayo Clinic score; PBO: placebo.

Disclosure: The authors report disclosures (research grants/funding/consulting fees/speakers’ bureau/speakers’ honoraria/lecture fees/advisory board/personal fees/shares/stock options) from Abbott, AbbVie, AdMIRx, AgomAb Therapeutics, Akebia Therapeutics, Alfresa Pharma, Alimentiv, Allakos, Allergan, Alma, Amgen, Applied Molecular Transport, Aptevo Therapeutics, Ardeypharm, Arena Pharmaceuticals, Asahi Kasei Medical Asta Pharmaceuticals, Aspen Japan, Astellas Pharma, AstraZeneca, AstraZeneca/MedImmune, Athos Therapeutics, Atlantic Healthcare, Atlantic Pharmaceuticals, Augurix, Avaxia Biologics, Avexegen Therapeutics, Avir Pharma, AYUMI Pharmaceutical, BeiGene, Biogen Idec, BiomX Israel, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calypso Biotech, Celgene, Celgene/Receptos, Celltech, Celltrion, Centocor, Conatus, Cosmo, EA Pharma, Egis, Elan/Biogen, EnGene, Enterome, Enthera, Escalier Biosciences, Everest Clinical Research Corp, FALK, Dr Falk Pharma, Ferring, Fisher, Flamentera, Forbion, Fresenius Kabi, Fujirebio, Galen/Atlantica, Galapagos, Genentech, Genentech, Inc./Hoffmann-La Roche, gIcare Pharma, Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Gramineer International, Hikma, Hospira, Inception IBD, Index Pharmaceuticals, Inotrem, Intact Therapeutics, Janssen, Japan Tobacco Company, JIMRO Co, Johnson & Johnson/Janssen, Kaken Pharmaceutical, Kissei Pharmaceutical, Kyorin Pharmaceutical, Kyowa Hakko Kirin, Kyowa Kirin Pharmaceutical Research, Landos Biopharma, Lexicon, Lilly, Lycera BioTech, Medimmune/AstraZeneca, Merck, Mesoblast Pharma, Millennium, Mitsubishi Tanabe Pharma, Miyarisan Pharmaceutical, Mochida Pharmaceutical, MSD, Mundipharma, Mylan, Nestle, Nextbiotix, Nichi-Iko Pharmaceutical, Nippon Kayaku, Norgine, Novartis, Novo Nordisk, OM Pharma, Oppilan Pharma, OSE Immunotherapeutics, Otsuka, Pandion Therapeutics, Par’Immune, Parvus Therapeutics, Pfizer, Phadia, Pharmacosmos, ProDigest, Progenity, Prometheus Biosciences, Protagonist, Qu Biologics, Rebiotix, Receptos, Reistone, Ritter Pharmaceuticals, Robarts Clinical Trials, Roche, Salix Pharma, Samsung Bioepis, Sandoz, Sanofi, Santarus, Second Genome, Series Therapeutics, Shire, Shoreline Biosciences, Sienna Biopharmaceuticals/Biologics, Sigmoid Biotechnologies/Pharma, Sterna Biologicals, Sublimity Therapeutics, Sun Pharma, Surrozen, Synergy Pharma, Taiho Pharmaceutical, Takeda, Teva Pharma, Theravance Biopharma, TiGenix, Tillotts Pharma, UCB Pharma, Ventyx Biosciences, Vertex Pharma, VHsquared, Vifor Pharma, Vimalan Biosciences, Vital Solutions, Vivelix Pharmaceuticals, Zeria Pharmaceutical, Zeller, Zydus, Zyngenia; employment and shares with Galapagos (CT, RB); and employment and shares with Gilead (JM, CY, SZ, XL). RF and IH have nothing to disclose.

LB20 Efficacy and safety of filgotinib as induction therapy for patients with moderately to severely active ulcerative colitis: Results from the Phase IIB/III SELECTION study

BG Feagan¹, EV Loftus Jr ², S Danese³, S Vermeire⁴, WJ Sandborn⁵, T Ritter⁶, R Mehta⁷, U Seidler⁸, F Seibold⁹, I Beales¹⁰, HJ Kim¹¹, J McNally¹², C Yun¹², S Zhao¹², X Liu¹², C Tasset¹³, R Besuyen¹⁴, M Watanabe¹⁵, S Schreiber¹⁶, G Rogler¹⁷, T Hibi¹⁸, L Peyrin-Biroulet¹⁹

¹Western University, London, Canada

²Mayo Clinic College of Medicine, Rochester, USA

³Humanitas University, Milan, Italy

⁴University Hospitals Leuven, Leuven, Belgium

⁵University of California San Diego, La Jolla, USA

⁶GI Alliance, Southlake, USA

⁷Surat Institute of Digestive Science (SIDS), Surat, India

⁸Hannover Medical School, Hannover, Germany

⁹Seibold and Partner Crohn’s Colitis Center, Gastroenterological Practice Balsiger, Bern, Switzerland

¹⁰Norfolk and Norwich University Hospital, Norwich, UK

¹¹Kyung Hee University Hospital, Center for Crohn’s and Colitis, Seoul, Republic of Korea

¹²Gilead Sciences, Inc., Foster City, USA

¹³Galapagos NV, Mechelen, Belgium

¹⁴Galapagos BV, Leiden, The Netherlands

¹⁵Tokyo Medical and Dental University, Tokyo, Japan

¹⁶University Hospital Schleswig-Holstein, Department of Medicine I and Institute for Clinical Molecular Biology, Kiel, Germany

¹⁷University Hospital of Zurich, Zurich, Switzerland

¹⁸Kitasato University Kitasato Institute Hospital, Center for Advanced IBD Research and Treatment, Tokyo, Japan

¹⁹Lorraine University, Nancy University Hospital and Inserm U1256 NGERE, Vandoeuvre-les-Nancy, France

Contact e-mail address: brian.feagan@robartsinc.com

Introduction

Filgotinib (FIL) is a Janus kinase 1 inhibitor being investigated for several inflammatory conditions, including ulcerative colitis (UC).

Aims and methods: The SELECTION (NCT02914522) induction studies aimed to evaluate the efficacy and safety of FIL as induction therapy for patients with moderately to severely active UC who were biologic naïve but failed conventional therapy (Cohort A Induction Study) or who had failed prior biologics (Cohort B Induction Study). In both induction studies, patients were randomized 2:2:1 to once-daily FIL 200 mg, FIL 100 mg, or placebo (PBO). The primary endpoint for both studies was endoscopic/rectal bleeding/stool frequency (EBS) remission at week 10, defined by Mayo endoscopic subscore (ES) ≤1, rectal bleeding subscore = 0, and ≥1-pt decrease in stool frequency subscore from baseline and stool frequency subscore ≤1. Key secondary endpoints included Mayo Clinic score (MCS) remission, endoscopic remission (ES = 0), and Geboes histologic remission at week 10.

Results

In both cohorts, baseline demographics, UC disease characteristics and concomitant UC medications were generally similar across treatment groups. In Cohort A, 659 patients were randomized and treated. At baseline, mean MCS was 8.6, and 56% of patients had severe endoscopic disease (ES = 3). Overall, 625 (95%) completed treatment; the most common reason for treatment discontinuation was an adverse event (AE). A significantly higher proportion of patients treated with FIL 200 mg achieved EBS remission vs. PBO. In addition, a significantly higher proportion of patients treated with FIL 200 mg vs. PBO achieved all key secondary endpoints (Table). In Cohort B, 689 patients were randomized and treated. At baseline, mean MCS was 9.3, and 78% of patients had ES = 3. Approximately 86% were prior anti-TNF failures, 52% were prior vedolizumab failures and 43% had failed both. Overall, 635 (92%) completed treatment; the most common reason for treatment discontinuation was an AE. A significantly higher proportion of patients receiving FIL 200 mg achieved EBS remission vs. PBO (Table). Overall, the incidence of AEs, serious AEs, and discontinuations due to AEs were similar across FIL and PBO treatment groups during the induction period. In PBO, FIL 100 mg and FIL 200 mg groups, serious infection occurred in 0.7%, 0.7%, and 0.4% of patients in Cohort A and in 1.4%, 1.4%, and 0.8% of patients in Cohort B; herpes zoster infection occurred in 0%, 0%, and 0.8% of patients in Cohort A and in 0%, 0.4%, and 0.4% of patients in Cohort B. One patient on FIL 200 mg experienced an opportunistic infection of mild esophageal candidiasis on day 15 that resolved with treatment. One patient on FIL 200 mg experienced a serious AE of pulmonary embolism on Day d9; the patient’s medical history was significant for hypothyroidism and pulmonary symptoms of unknown origin.

Conclusion

The SELECTION study population included a high proportion of dual-refractory patients and patients with severe endoscopic disease. Both doses of FIL were well tolerated. Filgotinib 200 mg was effective as an induction treatment for both biologic-naïve and biologic-experienced patients with moderately to severely active UC.

Abstract No: LB20.

Efficacy Summary for Cohort A and Cohort B

	Cohort A Induction Study (biologic naïve)				Cohort B Induction Study (biologic experienced)
	PBO (N = 137)	FIL 100 mg (N = 277)	FIL 200 mg (N = 245)	Δ% FIL 200 mg vs. PBO (95% CI); p-value	PBO (N = 142)	FIL 100 mg (N = 285)	FIL 200 mg (N = 262)	Δ% FIL 200 mg vs. PBO (95% CI); p-value
EBS remission, n (%)	21 (15.3)	53 (19.1)	64 (26.1)	10.8 (2.1, 19.5); p = 0.0157	6 (4.2)	27 (9.5)	30 (11.5)	7.2 (1.6, 12.8), p = 0.0103
MCS remission, n (%)	17 (12.4)	47 (17.0)	60 (24.5)	12.1 (3.8, 20.4); p = 0.0053	6 (4.2)	17 (6.0)	25 (9.5)	5.3 (−0.1, 10.7); p = 0.0393
Endoscopic remission, n (%)	5 (3.6)	16 (5.8)	30 (12.2)	8.6 (2.9, 14.3); p = 0.0047	3 (2.1)	6 (2.1)	9 (3.4)	1.3 (−2.5, 5.1); p = 0.4269
Geboes histologic remission, n (%)	22 (16.1)	66 (23.8)	86 (35.1)	19.0 (9.9, 28.2); p<0.0001	12 (8.5)	39 (13.7)	52 (19.8)	11.4 (4.2, 18.6); p = 0.0019

EBS remission = endoscopic subscore ≤1, rectal bleeding subscore = 0, and ≥1-pt decrease in stool frequency subscore from baseline and stool frequency subscore ≤1; MCS remission = MCS ≤2 and no single subscore >1; endoscopic remission = Mayo endoscopic subscore = 0; Geboes histologic remission = Grade 0 of ≤0.3, Grade 1 of ≤1.1, Grade 2a of ≤2A.3, Grade 2b of 2B.0, Grade 3 of 3.0, Grade 4 of 4.0, and Grade 5 of 5.0.

CI: confidence interval; EBS: endoscopy/bleeding/stool; FIL: filgotinib; MCS: Mayo Clinic score; PBO: placebo.

Disclosure: The authors report disclosures (research grants/funding/consulting fees/speakers’ bureau/speakers’ honoraria/lecture fees/advisory board/personal fees/shares/stock options) from Abbott, AbbVie, AdMIRx, Inc., AgomAb Therapeutics, Akebia Therapeutics, Alfresa Pharma, Alimentiv, Allakos, Allergan, Alma, Amgen, Applied Molecular Transport, Aptevo Therapeutics, Ardeypharm, Arena Pharmaceuticals, Asahi Kasei Medical Asta Pharma, Aspen Japan, Astellas Pharma, AstraZeneca, AstraZeneca/MedImmune, Athos Therapeutics, Atlantic Healthcare, Atlantic Pharmaceuticals, Augurix, Avaxia Biologics, Avexegen Therapeutics, Avir Pharma, AYUMI Pharmaceutical, BeiGene, Biogen Idec, BiomX Israel, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calypso Biotech, Celgene, Celgene/Receptos, Celltech, Celltrion, Centocor, Conatus, Cosmo, EA Pharma, Elan/Biogen, EnGene, Enterome, Enthera, Escalier Biosciences, Everest Clinical Research Corp, FALK, Dr Falk Pharma, Ferring, Fisher, Flamentera, Forbion, Fresenius Kabi, Fujirebio, Galen/Atlantica, Galapagos, Genentech, Genentech, Inc./Hoffmann-La Roche, gIcare Pharma, Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Hikma, Hospira, Inception IBD, Index Pharmaceuticals, Inotrem, Intact Therapeutics, Intercept, Ironwood, Janssen, Japan Tobacco Company, JIMRO Co, Johnson & Johnson/Janssen, Kaken Pharmaceutical, Kissei Pharmaceutical, Kyorin Pharmaceutical, Kyowa Hakko Kirin, Kyowa Kirin Pharmaceutical Research, Landos Biopharma, Lexicon, Lilly, Lycera BioTech, Medimmune/AstraZeneca, Merck, Mesoblast Pharma, Millennium, Mitsubishi Tanabe Pharma, Miyarisan Pharmaceutical, Mochida Pharmaceutical, MSD, Mundipharma, Mylan, Nestle, Nextbiotix, Nichi-Iko Pharmaceutical, Nippon Kayaku, Norgine, Novartis, Novo Nordisk, OM Pharma, Oppilan Pharma, OSE Immunotherapeutics, Otsuka, Pandion Therapeutics, Par’Immune, Parvus Therapeutics, Perspectum, Pfizer, Phadia, Pharmacosmos, ProDigest, Progenity, Prometheus Biosciences, Protagonist, Qu Biologics, Rebiotix, Receptos, Reistone, Ritter Pharmaceuticals, Robarts Clinical Trials, Roche, Salix Pharma, Samsung Bioepis, Sandoz, Sanofi, Santarus, Second Genome, Series Therapeutics, Shire, Shoreline Biosciences, Sienna Biopharmaceuticals/Biologics, Sigmoid Biotechnologies/Pharma, Sterna Biologicals, Sublimity Therapeutics, Surrozen, Synergy Pharma, Taiho Pharmaceutical, Takeda, Teva Pharma, Theravance Biopharma, TiGenix, Tillotts Pharma, UCB Pharma, Ventyx Biosciences, Vertex Pharma, VHsquared, Vifor Pharma, Vimalan Biosciences, Vital Solutions, Vivelix Pharmaceuticals, Zeria Pharmaceutical, Zeller, Zyngenia; employment and shares with Galapagos (CT, RB); and employment and shares with Gilead (JM, CY, SZ, XL). RM has nothing to disclose.

LB21 An investigational oral microbiome drug, CP101, for the prevention of recurrent Clostridioides difficile infection: A randomized, placebo-controlled, multi-center trial (PRISM3)

JR Allegretti^1,2, CR Kelly^3,4, T Louie⁵, M Fisher⁶, S Hota^7,8, B Misra⁹, NW Van Hise¹⁰, E Yen¹¹, JS Bullock¹², J Pullman¹³, M Silverman^14,15, I Davis¹⁶, S McGill¹⁷, S Budree¹⁸, S Khanna¹⁹, D Pardi¹⁹, R Orenstein²⁰, A Grinspan²¹, N El-Nachef²², C Kraft²³, TJ Borody²⁴, Z Kassam¹⁸

¹Brigham and Women’s Hospital, Boston, USA

²Harvard Medical School, Boston, USA

³Warren Alpert Medical School of Brown University, Providence, USA

⁴Women’s Gastrointestinal Medicine, Providence, USA

⁵University of Calgary, Calgary, Canada

⁶Indiana University, Indianapolis, USA

⁷University of Toronto, Toronto, Canada

⁸University Health Network, Toronto, Canada

⁹Borland Groover Clinic, Jacksonville, USA

¹⁰Metro Infectious Disease Consultants, Burr Ridge, USA

¹¹NorthShore University HealthSystem, Evanston, USA

¹²Southern Star Research Institute, San Antonio, USA

¹³Mercury Street Medical, Butte, USA

¹⁴St. Joseph’s Health Care, London, Canada

¹⁵Western University, London, Canada

¹⁶Dalhousie University, Halifax, Canada

¹⁷University of North Carolina Hospitals, Chapel Hill, USA

¹⁸Finch Therapeutics, Somerville, USA

¹⁹Mayo Clinic, Rochester, USA

²⁰Mayo Clinic, Scottsdale, USA

²¹Mount Sinai Hospital, New York, USA

²²University of California San Francisco, San Francisco, USA

²³Emory University Hospital, Atlanta, USA

²⁴Center for Digestive Diseases, Sydney, Australia

Contact e-mail address: jallegretti@bwh.harvard.edu

Introduction

Recurrent Clostridioides difficile infection (CDI) is common following CDI antibiotics, and disruption of the gut microbiome is key to pathogenesis. There is a paucity of placebo-controlled trials assessing oral microbiome therapeutics. This study evaluated CP101, an investigational oral microbiome drug designed to restore microbiome diversity and prevent CDI recurrence in a broad population.

Aims and Methods: We conducted a double-blind, randomized, placebo-controlled trial involving adults who received standard-of-care (SOC) antibiotics for recurrent CDI at 51 sites in the USA and Canada. Patients with first CDI recurrence at high-risk for further recurrence (≥65 years), or those with two or more recurrences were eligible. The qualifying CDI episode was diagnosed prior to study entry by guideline recommended testing methods (PCR-based or Toxin EIA-based testing). Following completion of the most recent course of CDI antibiotics, eligible participants were randomized 1:1 to receive one-time oral administration of CP101 (6 × 10¹¹ cell count) or placebo. The primary endpoint was sustained clinical cure, defined as an absence of CDI recurrence through week 8 following dosing.

Results

In total, 198 enrolled participants were analyzed, with 27.5% of participants having one CDI recurrence prior to study entry and 62.7% of the qualifying CDI episodes diagnosed by PCR-based testing. Baseline characteristics were similar between CP101 (n = 102) or placebo (n = 96) arms (Table). Following SOC antibiotics, the proportion of sustained clinical cure was significantly higher with CP101 than placebo (relative risk reduction (RRR) 21%; 74.5% (76/102) vs. 61.5% (59/96), p = 0.0488). In a per-protocol analysis determined prior to unblinding (n = 166), sustained clinical cure was also significantly higher with CP101 than placebo (RRR 33%; 73.5% (61/83) vs. 55.4% (46/83), p = 0.0150). Time-to-event analysis showed a statistically significant benefit, favoring CP101 compared to placebo (p = 0.0139). CP101 was well-tolerated, and there were no treatment-related serious adverse events.

Conclusion

This is the largest randomized, placebo-controlled trial of an investigational oral microbiome drug. Following any SOC antibiotic course, CP101 resulted in a significant and clinically meaningful reduction in recurrent CDI compared to placebo. Importantly, CP101 resulted in the prevention of recurrence across a broad population, including patients with first CDI recurrence and diagnosis by any guideline approved CDI diagnostic method.

Abstract No: LB21Table 1.

Clinical and Demographic Characteristic

Characteristics	CP101 (N=102)	Placebo (N=96)	Total (N=198)
Age (years), M (SD)	65.9 (17.3)	66.5 (14.3)	66.2 (15.8)
Female sex, n (%)	69 (67.6)	65 (67.7)	134 (67.7)
Charlson comorbidity index, M (SD)	3.9 (2.9)	3.8 (2.7)	3.9 (2.8)
CARDS, M (SD)	3.3 (1.9)	3.1 (1.5)	3.2 (1.7)
Number of CDI recurrences, n (%)
First recurrence	28 (27.5)	29 (30.2)	57 (28.8)
Second or further recurrence	73 (71.6)	67 (69.8)	140 (70.7)
NR	1 (1.0)	0 (0.0)	1 (0.5)
CDI laboratory test at study entry, n (%)
PCR-based testing (alone or in combination)	64 (62.7)	57 (59.4)	121 (61.1)
Toxin EIA-based testing (alone or in combination)	36 (35.3)	38 (39.6)	74 (37.4)
NR	2 (2.0)	1 (1.0)	3 (1.5)
SOC CDI antibiotic at study entry, n (%)
Oral vancomycin (alone or in combination)	87 (85.3)	84 (87.5)	171 (86.4)
Oral fidaxomicin (alone or in combination)	21 (20.6)	19 (19.8)	40 (20.2)
Oral metronidazole (alone or in combination)	2 (2.0)	4 (4.2)	6 (3.0)
Other	1 (1.0)	0 (0.0)	1 (0.5)

CARDS: C. difficile Risk of Death Score; CDI: C. difficile infection; NR: not reported; SD: standard deviation; SOC: standard-of-care

*For PRISM3 investigators.

Disclosure: JRA—clinical trial research: Finch Therapeutics; scientific advisory board: Finch Therapeutics, Iterative Scopes; consulting: Pandion, Pfizer, Servatus, Takeda, Janssen; research support: Merck; advisory board (unpaid): OpenBiome. CK—clinical trial research: Finch Therapeutics; clinical advisory board: OpenBiome. TL—clinical trial research: Finch Therapeutics, Summit PLC, Rebiotix, MGB Biopharma, Immunimed, Vedanta, Seres Therapeutics; consultant: Davoterra and Crestone. MF—clinical trial research: Finch Therapeutics; advisory board (unpaid): OpenBiome; DSMB: Rebiotix/Ferring. SH—clinical trial research: Finch Therapeutics. BM—clinical trial research: Finch Therapeutics. NWVH—clinical trial research: Finch Therapeutics; speakers’ bureau: Melinta Therapeutics. EY—clinical trial research: Finch Therapeutics. JSB—clinical trial research: Finch Therapeutics. JP—clinical trial research: Finch Therapeutics. MS—clinical trial research: Finch Therapeutics. ID—clinical trial research: Finch Therapeutics. SMcG—clinical trial research: Finch Therapeutics. SB—employee and shareholder: Finch Therapeutics. SK—clinical trial research: Rebiotix, Finch, Seres, Vedanta; consulting: Shire, Probiotech, Facile, Jetson. DP—consulting: Assembly Bioscience, Otsuka, Seres, Gilead, Vedanta; clinical trial research: Atlantic, Finch, Janssen, Pfizer, Salix, Seres, Takeda. VRO—clinical trial research: Finch, Vedanta, Rebiotix. AG—clinical trial research: Finch Therapeutics; speakers’ bureau: Merck. NEN—clinical trial research: Finch Therapeutics; consultant: Federation Bio. CK—clinical trial research: Finch Therapeutics; scientific advisory board: Rebiotix. TJB—medical director, employee, consultant, patent holder, grant/research support, stockholder/ownership interest and advisory committee/board member: Centre for Digestive Diseases in Australia; advisory committee/board member: Axent Medical Pty Ltd in Australia; advisory committee/board member, patent holder, stockholder/ownership interest: Finch Therapeutics in the USA; scientific advisory board member, stockholder/ownership interest: RedHill Biopharma in the USA. ZK—employee and shareholder: Finch Therapeutics

LB22 Dupilumab efficacy and safety in adult and adolescent patients with eosinophilic esophagitis: Results from PART A of a randomized, placebo-controlled three-part, Phase III study

ES Dellon¹, ME Rothenberg², MH Collins², I Hirano³, M Chehade⁴, A Bredenoord⁵, AJ Lucendo⁶, JM Spergel⁷, Q Zhao⁸, JD Hamilton⁸, B Beazley⁸, I Guillemin⁹, S Kamat⁸, L Mannent⁹, M Ruddy⁸, E Laws¹⁰, B Akinlade⁸, N Amin⁸, A Radin⁸, B Shumel⁸, J Maloney⁸, Co-last authors

¹University of North Carolina School of Medicine, Chapel Hill, USA

²Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, USA

³Northwestern University Feinberg School of Medicine, Division of Gastroenterology, Chicago, USA

⁴Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, USA

⁵Amsterdam University Medical Center, Department of Gastroenterology, Amsterdam, The Netherlands

⁶Hospital General de Tomelloso, Department de Gastroenterology, Tomelloso, Spain

⁷Children’s Hospital of Philadelphia, Philadelphia, USA

⁸Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA

⁹Sanofi, Chilly-Mazarin, France

¹⁰Sanofi, Bridgewater, USA

Contact e-mail address: evan_dellon@med.unc.edu

Introduction

Eosinophilic esophagitis (EoE) is a chronic type 2 inflammatory disease of the esophagus that can substantially impair patients’ quality of life. Treatment options are limited, and patient response to current standard of care is generally suboptimal. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation in EoE. In a Phase III proof-of-concept study, dupilumab significantly improved histological and clinical outcomes of EoE with an acceptable safety profile. Part A of a three-part, randomized, placebo-controlled Phase III study (NCT03633617) evaluated the efficacy and safety of weekly dupilumab 300 mg vs. placebo in adult and adolescent patients with EoE for 24 weeks of treatment.

Aims and methods: In total, 81 patients were randomized 1:1 to receive dupilumab (42 patients) or placebo (39 patients) for 24 weeks. Co-primary endpoints were the proportion of patients achieving a peak esophageal intraepithelial eosinophil (eos) count of ≤6 eos/high-power field (hpf), and the absolute change in Dysphagia Symptom Questionnaire (DSQ) score from baseline to week 24. Secondary endpoints included percent change in peak esophageal intraepithelial eos count, absolute change from baseline in total EoE endoscopic reference score (EREFS), proportion of patients achieving a peak eos count of <15 eos/hpf, and change from baseline in gene expression as measured by normalized enrichment score (NES) using the EoE diagnostic panel (EDP) or type 2 inflammatory genes.

Results

Baseline characteristics were comparable in both treatment groups. At week 24, a significantly higher proportion of patients treated with dupilumab vs. placebo achieved a peak eos count of ≤6 eos/hpf (59.5% vs. 5.1%, p<0.001; Table) and <15 eos/hpf (64.3% vs. 7.7%, p<0.001). Dupilumab-treated patients had a significantly greater percent change from baseline in peak eos count (LS mean difference −68.26% (95% CI −86.90 to −49.62), p<0.001); significantly greater change in DSQ score (LS mean difference −12.32 (95% CI −19.11 to −5.54)], p<0.001); and significantly greater change in total EREFS (LS mean difference −2.9 (95% CI −3.91 to −1.84), p<0.001) compared with placebo. Dupilumab, but not placebo, significantly suppressed both the EDP NES and type 2 inflammation NES. Dupilumab was generally well tolerated; the most common treatment-emergent adverse events for dupilumab vs. placebo were injection-site reactions (16.7% vs. 10.3%) and nasopharyngitis (11.9% vs. 10.3%).

Conclusion

In this Phase III study, weekly dupilumab demonstrated significant and clinically meaningful improvements in histologic, symptomatic, endoscopic, and molecular aspects of EoE, and was well tolerated with an acceptable safety profile.

Abstract No: LB22.

Summary of Co-primary and Secondary Outcomes at Week 24 in Part A of the Phase III EoE study

Outcomes at week 24a	Placebo (N=39)	Dupilumab 300 mg qw (N=42)	Difference dupilumab vs. placebo (95% CI)	p-Value for dupilumab vs. placebo
Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf, n (%)b	n=39 2 (5.1)	n=42 25 (59.5)	55.3 (39.58 to 71.04)	<0.001
Absolute change in DSQ score, LS mean (SE)c	n=28/11d –9.60 (2.79)	n=38/4d –21.92 (2.53)	–12.32 (–19.11 to –5.54)	<0.001
Percent change in peak eosinophil count (eos/hpf), LS mean (SE)b	n=26/13d –2.98 (7.60)	n=35/7d –71.24 (6.95)	–68.26 (–86.90 to –49.62)	<0.001
Absolute change in total EoE-EREFS, LS mean (SE)e	n=26/13d –0.3 (0.41)	n=35/7d –3.2 (0.41)	–2.9 (–3.91 to –1.84)	<0.001
Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf, n (%)b	n=39 3 (7.7)	n=42 27 (64.3)	57.5 (41.69 to 73.33)	<0.001
Change in NES of the EDP gene signature, medianb,f	n=25/4d –0.16	n=31/0d –2.66	–2.25 (–2.72 to –1.73)	<0.001
Change in NES score of the type 2 inflammation gene signature, medianb,g	n=25/4d –0.32	n=31/0d –1.97	–1.59 (–1.74 to –1.27)	<0.001

^aEndpoints are listed in the order of their position in the hierarchy; values after first rescue treatment used were set to missing (censoring).

^bPinch biopsies were collected from three esophageal regions (proximal, mid, distal) at screening and week 24 for histology and RNA sequencing.

^cThe Dysphagia Symptom Questionnaire is a patient-reported outcome measure that is administered daily and assesses the frequency and severity of dysphagia. The biweekly total DSQ score ranges from 0 to 84; lower scores indicate less dysphagia-related symptom burden.

^dn=number of observed/imputed patients. Five patients in the placebo group received rescue treatment; data after rescue treatment were set to missing and their week 24 data were imputed.

^eEndoscopies were performed at screening and week 24, and the proximal and distal esophageal regions scored for edema, rings, exudates, furrows, and strictures. The overall score ranges from 0 to 18; higher scores indicate greater severity.

^fMean gene expression of the three esophageal regions for each patient per time point was examined, and NESs were generated using the EDP, a 96-gene panel of genes differentially expressed in esophageal pinch biopsies from EoE patients vs. controls.¹

^gMean gene expression of the three esophageal regions for each patient per time point was examined, and NESs were generated using an in-house curated list of genes associated with type 2 inflammation.

CI: confidence interval; DSQ: Dysphagia Symptom Questionnaire; EDP: EoE diagnostic panel; EoE: eosinophil esophagitis; eos: eosinophils; EREFS: endoscopic reference score; hpf: high-power field; LS: least squares; NES: normalized enrichment score; qw: every week; SE: standard error.

Disclosure: ESD: Abbott, Adare, Aimmune, Allakos, Amgen, Arena, AstraZeneca, Biorasi, Calypso, Eli Lilly, EsoCap, GlaxoSmithKline, Gossamer Bio, Parexel, Receptos/Celgene/Bristol Myers Squibb, Regeneron Pharmaceuticals, Inc., Robarts, Salix, Shire/Takeda—consultant; Adare, Allakos, GlaxoSmithKline, Meritage, Miraca, Nutricia, Receptos/Celgene/Bristol Myers Squibb, Regeneron Pharmaceuticals, Inc., Shire/Takada—research funding; Allakos, Banner, Holoclara—educational grant. MER: Allakos, AstraZeneca, Bristol Myers Squibb, ClostraBio, PulmOne, Spoon Guru—consultant; ClostraBio, PulmOne, Spoon Guru—equity interest; Teva Pharmaceuticals—royalties from reslizumab; Mapi Research Trust—royalties from PEESSv2; UpToDate—royalties; inventor of patents owned by Cincinnati Children’s Hospital. MHC: Allakos, Arena, AstraZeneca, Bristol Myers Squibb, Calypso, EsoCap, GlaxoSmithKline, Regeneron Pharmaceuticals, Inc., Shire—consultant; Receptos/Bristol Myers Squibb, Regeneron Pharmaceuticals, Inc., Shire—research funding. IH: Adare, Receptos/Bristol Myers Squibb, Regeneron Pharmaceuticals, Inc., Shire—consultant; Meritage, Receptos/Bristol Myers Squibb, Regeneron Pharmaceuticals, Inc., Shire—research funding. MC: Adare, Allakos, AstraZeneca, Nutricia, Regeneron Pharmaceuticals, Inc., Shire—consultant; Allakos, Regeneron Pharmaceuticals, Inc., Shire—research funding; Medscape, Nutricia—honoraria for lectures. AJB: Arena, AstraZeneca, Calypso, Dr Falk Pharma, EsoCap, Gossamer Bio, Laborie, Medtronic, RB, Regeneron Pharmaceuticals, Inc., Robarts—consultant; Bayer, Nutricia, SST—research funding; SST—equity interest. AJL: EsoCap, Dr Falk Pharma—consultant; Dr Falk Pharma, Regeneron Pharmaceuticals, Inc.—research funding. JMS: Allakos, DBV Technologies, Novartis, Regeneron Pharmaceuticals, Inc., Shire, Takeda—consultant; DBV Technologies, Regeneron Pharmaceuticals, Inc.—grant support. QZ, JDH, BB, SK, MR, BA, NA, AA, BS, JM: Regeneron Pharmaceuticals, Inc.—employees and shareholders. IG: Sanofi—prior employee, may hold stock and/or stock options in the company. LM, EL: Sanofi—employees, may hold stock and/or stock options in the company.

Reference

1. Wen T, et al. Molecular diagnosis of eosinophilic esophagitis by gene expression profiling. Gastroenterology 2013; 145: 1289–1299.

LB23 Immunosuppressive treatment is not a risk factor to develop a worse SARS-CoV-2 infection in elderly IBD patients: An observational, descriptive, cohort study

M Calafat Sard¹, C Gonzalez Muñoza², M Fortuny¹, C Roig², A Calm¹, A Mombiela², F Cañete^1,3, F Bertoletti², M Mañosa Ciria^1,3, J Gordillo², E García-Planella², E Domenech Morral^1,3

¹Hospital Universitari Germans Trias i Pujol, Badalona, Spain

²Hospital del la Santa Creu i Sant Pau, Barcelona, Spain

³CIBEREHD, Madrid, Spain

Contact e-mail address: margalidasard.calafat@gmail.com

Introduction

In the general population, elderly age has been reported as a risk factor for developing a SARS-CoV-2 infection (COVID-19) with a worse prognosis. Although it has not been proven, patients under immunosuppressive treatment (IST) are expected to have a worse COVID-19 prognosis, probably due the known higher risk of developing viral infections. Moreover, there are scarce data related about COVID-19 in inflammatory bowel disease (IBD) patients under IST and none focusing in elderly IBD.

Aims and methods: This study aimed to describe and compare the incidence of COVID-19 in IBD patients >65 years of age with and without IST during the pandemic in Catalonia, Spain. IBD patients >65 years of age on January 2020 were selected from two referral IBD centers in the Barcelona area and grouped into two cohorts regarding the use or not of IST (thiopurines or methotrexate). Patients under biological treatment (in monotherapy or in combination) were excluded. We recorded the confirmed COVID-19 (PCR positive) during the follow-up period (1 March to 30 April), adherence to IST (defined as to have an active drug electronic prescription and delivery at least once during the study period), demographic data, IBD co-morbidities and concomitant non-IBD related treatments.

Results

Out of 476 IBD elderly patients, 417 (88%) patients were selected, and 59 (12%) patients who were under biological treatment were excluded. The patients’ median age was 73 years (IQR 69–78 years); 52% were male; 70% had ulcerative colitis, 28% Crohn’s disease and 2% unclassifiable colitis; 60% had arterial hypertension, 22% diabetes mellitus, 22% cardiovascular disease, 15% chronic obstructive pulmonary disease, 10% chronic renal disease, 5% were active smokers. Sixty per cent of patients received anti-hypertensive treatment, and 22% received anti-diabetic agents. From the total cohort, 88 (20%) patients were under IST (85 patients with thiopurines, three with methotrexate). The median time on IST was 121 months (IQR 60–162 months). Seventeen (19%) patients in the IST cohort were considered to be not adherent to IST. In the whole cohort, COVID-19 was confirmed in only four (1%) patients, two of whom were under IST (one with azathioprine, and the other with methotrexate), but only the one receiving azathioprine was adherent to IST during the follow-up period. When we compared both cohorts, the proportion of COVID-19 was 0.6% without IST vs. 2.3% under IST, with no differences between both groups (p = 0.155). All four patients required hospital admittance: two of them (one with IST and the other without IST) developed COVID-19-related complications (thromboembolic and cardiological), and one patient, who did not receive IST, died.

Conclusion

COVID-19 incidence in elderly IBD patients in our IBD population was low, although it required hospitalization and developed infection-related complications in most of them, as observed in the general elderly background population. Despite this, IST does not appear to increase the risk of COVID-19 infection in elderly IBD patients.

Disclosure: Nothing to disclose.

LB24 Gastrointestinal symptoms and complications of COVID-19: An international multicenter prospective cohort study (TIVURON project)

K Cárdenas-Jaén¹, SA Sánchez-Luna², A Vaillo-Rocamora¹, M Riat Castro Zocchi³, D Useros Brañas⁴, L Guberna Blanco³, JM Remes-Troche⁵, A Ramos de la Medina⁵, BA Priego-Parra⁵, JA Velarde-Ruiz Velasco⁶, P Martínez-Ayala⁶, A Urzúa-Manchego⁷, D Guíñez Francois⁸, KM Pawlak⁹, K Kozłowska-Petriczko¹⁰, I Gorroño-Zamalloa¹¹, C Urteaga Casares¹¹, I Ortiz Polo¹², A del Val Antonana¹², EE Lozada Hernández¹³, E Obregón Moreno¹³, G García-Rayado¹⁴, MJ Domper Arnal¹⁴, D Casas Deza¹⁵, EI Esteban Cabello¹⁶, LA Díaz¹⁷, A Riquelme Pérez¹⁷, H Martinez Lozano¹⁸, F Navarro Romero¹⁹, I Olivas²⁰, G Iborra Muñoz²¹, A Calero²², I Caravaca²², R Pastor Mateu²³, B Lapeña Muñoz²⁴, V Sastre Lozano²⁵, NM Pizarro Vega²⁶, L Melcarne²⁷, E de-Madaria²⁸

¹Alicante University General Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Gastroenterology, Alicante, Spain

²Center for Advanced Therapeutic Endoscopy, Allegheny Health Network/Allegheny Center for Digestive Health, Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh, USA

³Hospital Universitario de La Princesa e Instituto de Investigación Sanitaria Princesa (IIS-IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Servicio de Aparato Digestivo, Madrid, Spain

⁴Hospital Universitario de La Princesa e Instituto de Investigación Sanitaria Princesa (IIS-IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Medicina Interna, Madrid, Spain

⁵Hospital Español de Veracruz. Instituto de investigaciones Medico Biológicas de la Universidad Veracruzana, Servicio de Aparato Digestivo, Veracruz, Mexico

⁶Hospital Civil de Guadalajara Fray Antonio Alcalde, Servicio de Gastroenterología, Guadalajara, Mexico

⁷Hospital Clínico Universidad de Chile, Sección de GastroenterologÍa. Departamento de Medicina, Santiago de Chile, Chile

⁸Hospital Clínico Universidad de Chile., Sección de Medicina Interna. Departamento de Medicina., Santiago de Chile, Chile

⁹Hospital of the Ministry of Interior and Administration, Department of Gastroenterology, Szczecin, Poland

¹⁰SPWSZ Hospital, Department of Gastroenterology and Internal Medicine, Szczecin, Poland

¹¹Hospital Universitario de Alava, Servicio de Aparato Digestivo, Unidad de pancreas., Vitoria-Gasteiz, Spain

¹²Hospital Universitario y Politecnico la fe, Servicio de Medicina Digestiva, Valencia, Spain

¹³Hospital regional de alta especialidad del Bajío, Servicio de Cirugía General, Leon-Guanajuato, Mexico

¹⁴Hospital Clínico Universitario Lozano Blesa, Zaragoza. Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Servicio de Aparato Digestivo, Zaragoza, Spain

¹⁵Hospital Universitario Miguel Servet, Servicio de Aparato Digestivo, Zaragoza, Spain

¹⁶Hospital Universitario Miguel Servet, Servicio de Medicina Interna, Zaragoza, Spain

¹⁷Faculty of Medicine. Pontificia Universidad Católica de Chile., Department of Gastroenterology, Santiago de Chile, Chile

¹⁸Hospital General Universitario e Instituto de Investigación Sanitaria Gregorio Marañón, Madrid,Facultad de Medicina, Universidad Complutense de Madrid; y CiberEHD, Servicio de Aparato Digestivo., Madrid, Spain

¹⁹Hospital Costa del Sol, Servicio de Medicina Interna., Marbella, Spain

²⁰Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d’Investigacions Biomediques August Pi i S, Servicio de Aparato Digestivo, Barcelona, Spain

²¹Hospital de Mataró, Servicio de Digestivo, Mataró, Spain

²²Hospital General universitario de Elche, Servicio de Cirugía General y Digestiva, Elche, Spain

²³Consorcio Hospital General Universitario de Valencia, Servicio de Medicina digestiva, Valencia, Spain

²⁴Hospital San Pedro, Servicio Aparato Digestivo, Logroño, Spain

²⁵Hospital Universitario Santa Lucía, Servicio de Aparato Digestivo, Cartagena, Spain

²⁶Hospital Universitario De Fuenlabrada, Departamento de Aparato Digestivo, Fuenlabrada, Spain

²⁷Hospital Universitario Parc Tauli, Servicio de Aparato Digestivo, Sabadell, Spain

²⁸Alicante University General Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Departamento de Aparato Digestivo, Alicante, Spain

Contact e-mail address: kcjaen90@gmail.com

Introduction

The global spread of SARS-CoV-2 virus has resulted in a pandemic with significant social and health implications. Current clinical practice and several retrospective studies suggest that gastrointestinal (GI) symptoms are common in infected patients.

Aims and methods: The TIVURON project is an international multicenter prospective cohort study promoted by the Spanish Association of Gastroenterology (AEG). Its aim is to evaluate prospectively the GI symptoms and complications of COVID-19 in hospitalized patients. Patients hospitalized due to COVID-19 (defined as a positive PCR for SARS-CoV-2) from May 5 to August 31 2020 were prospectively recruited in 31 centers from Spain, Mexico, Chile, and Poland. Follow-up included the period between admission and 15 days after discharge.

Results

Preliminary analysis included 737 patients, with a mean age of 57 years (SD 18 years), 55.9% male. The median Charlson’s index was 2 points (IQR 0–4 points). The median time of hospitalization was seven days (IQR 5–11 days). Seventy-two (9.3%) patients required admission to the ICU; 27 (3.5%) patients died. The most frequent GI symptoms on admission were: anorexia (44.6%), diarrhea (35.5%), nausea (24.7%), and abdominal pain, mainly diffuse or epigastric (19%). At discharge and 15 days after discharge, symptoms resolved in most cases (prevalence <5%), except for anorexia, which persisted in 14.2% at the time of discharge, having resolved (<3%) 15 days after discharge. GI complications during admission were infrequent, except for increased transaminase blood levels (14.9%). Odynophagia (4.9%) was associated with higher mortality (17.2% vs. 5.7%, p = 0.015), greater need for ICU admission (46.7% vs. 12.4%, p = 0.000) and longer hospital stay (8.5 days vs. 7 days, p = 0.031). Constipation was associated with older age (63 years vs. 56 years, p = 0.004). Nausea (6 days vs. 8 days, p = 0.017), anorexia (7 days vs. 8 days, p = 0.030), and diarrhea (7 days vs. 8 days, p = 0.014) were associated with a shorter hospital stay. An increase in transaminase blood levels was associated with a greater need for ICU admission (24.3% vs. 11.9%, p = 0.002), mortality (11.3% vs. 4.7%, p = 0.014), and a longer hospital stay (9 days vs. 7 days, p = 0.001).

Conclusion

Anorexia, diarrhea, nausea, and abdominal pain are the most frequent digestive symptoms in hospitalized patients due to COVID-19. GI complications are rare, except for increased transaminase blood levels. Odynophagia and increased transaminase blood levels were associated with higher mortality, need for ICU admission and longer hospital stay. Nausea, anorexia, and diarrhea were associated with a shorter hospital stay.

Disclosure: Nothing to disclose.

LB25 Liver manifestations in COVID-19 and the influence of pre-existing liver disease in the course of the infection

C Vías Parrado, ML Cadena Herrera, P del Pino Bellido, MF Guerra Veloz, P Cordero Ruiz, F Bellido Muñoz, Á Caunedo Álvarez, I Carmona Soria

Hospital Universitario Virgen Macarena, Unidad Gestión Clínica de Gastroenterología y Hepatología, Seville, Spain

Contact e-mail address: carmen.viasparrado@gmail.com

Introduction

Some co-morbidities have been associated with a negative impact in the severity of COVID-19 course. Patients with advanced chronic liver disease (CLD) may be at increased risk of severe course due to the cirrhosis-associated immune dysfunction. However, actual data are scare. The aim of our study was to determine the prevalence of CLD in COVID-19 patients and to analyse the course of the infection comparing with patients with non-liver disease.

Aims and methods: This was a retrospective single-centre study in which we included all positive SARS-CoV-2 polymerase chain reactions (PCR) from 23 March to 30 April 2020. Clinical and biochemical data of patients with and without CLD and COVID-19 were collected using medical records.

Results

A total of 447 patients with SARS-CoV-2-positive PCR were included, of whom 6.3% had CLD. A total of 69.7% of patients with CLD were male, with a median age of 65.5 years, with active alcohol and smoke use. A total of 75% had non-advanced liver fibrosis, most of them non-alcoholic fatty liver disease (NAFLD). Patients with advanced liver fibrosis were younger, with a mean age of 58 years (SD 9.69 years), underlying chronic obstructive pulmonary disease (COPD; 57.2%). Meanwhile, patients with CLD without advanced liver fibrosis were older, with a mean age of 68 years (SD 12.08 years) and had multiples co-morbidities such as hypertension in 71.4% and diabetes in 47.6%. The hospital admission rate (92.9% vs. 47.7% p<0.001), concomitant co-morbidities (diabetes 38.5% vs. 16.5% p = 0.011; obesity 30.8% vs. 8.5% p = 0.033; cancer 23.1% vs, 5% p = 0.027; and COPD 19.2% vs. 9% p = 0.009) and concomitant antibiotics treatment (19.3% vs. 5%; p = 0.018) were higher in patients with CLD than those without CLD. The rate of intensive care admission, respiratory support (invasive mechanical ventilation (7.7% vs. 9.5%, p = 0.055) and continuous positive airway pressure CPAP or non-invasive positive pressure (19.2% vs. 19.0% p = 0.577)) and median stay length (8 days (5–15 days) vs. 7 days (5–13 days), p = 0.696) were similar in both groups. The inpatient hospital mortality rate was similar in both groups (30.8% vs. 19.6%, p = 0.289). The presence of CLD was not a risk factor associated with mortality (OR = 1.06; 95% CI 0.35–3.18; p = 0.924), like cardiovascular diseases (coronary artery disease (OR = 4.95; 95% CI 1.51–16.27; p = 0.008) and congestive heart failure (OR = 5.66; 95% CI 1.64–19.54; p = 0.006)). However, in univariate analysis, sex (male), presence of obesity and antibiotics concomitant treatment were associated risk factors for mortality in patients with CLD and COVID-19.

Conclusion

Patients with CLD had a low incidence of SARS-CoV-2 infection but a higher risk of hospital admission with worse outcomes associated with other concomitant co-morbidities and advanced fibrosis.

Abstract No: LB25.

Analysis of Predictors of Mortality in Patients with CLD and COVID-19

	Univariate OR (95% CI)	p
Age	0.989 (0.954–1.026)	0.562
Sex (male)	11.20 (1.25–100.31)	0.031
Smoker	12.67 (0.99–162.26)	0.051
COPD	5.25 (0.90–30.70)	0.066
Cancer	5.25 (0.90–30.70)	0.066
Obesity	7.20 (1.13–45.96)	0.037
Antibiotic treatment	12.00 (1.95–73.97)	0.007
Admission ALT >40	2.03 (0.38–10.69)	0.406
Ferritin	1.000 (0.999–1.000)	0.655

COPD: chronic obstructive pulmonary disease; ALT: alanine transaminase.

Disclosure: Nothing to disclose.

LB26 Telemedicine during the COVID-19 pandemic: Gastroenterological and nutritional video consultations were trusted by patients with inflammatory bowel diseases and celiac disease

A Costantino¹, D Noviello², L Elli¹, L Roncoroni¹, V Lombardo¹, S Mazza³, R Bertè², N Nandi², E Farina², A Scricciolo¹, L Scaramella², M Vecchi⁴, F Caprioli⁴

¹Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

²Università degli Studi di Milano, Milan, Italy

³Azienda Socio-Sanitaria Territoriale di Cremona, Cremona, Italy

⁴Università degli Studi di Milano, Fisiopatologia Medico-Chirurgica e dei Trapianti, Milan, Italy

Contact e-mail address: andreascostantino@gmail.com

Introduction

Telehealth is defined by the American Telemedicine Association (ATA) as ‘technology-enabled health and care management and delivery systems that extend capacity and access’.¹ It includes both health-care delivery (often identified as telemedicine) in terms of disease diagnosis and treatment and several other activities and services, such as prevention, education and public-health promotion.^2,3 During the recent COVID-19 pandemic, worldwide telemedicine has enabled many patients with chronic diseases to access remote assistance, since it has emerged as the ideal solution to overcome the restrictions to perform regular non-urgent follow-up visits to chronic patients and to continue patients’ assistance. Some positive reports on the use of telemedicine in gastroenterology among health-care providers and patients have been published, but a patient’s trust perspective about video consultations has been missing to date.^4–12

Aims and methods: Our study aimed to ascertain our gastroenterological patients’ trust in video consultations during the COVID-19 pandemic. At our Gastroenterology Unit in Milan (Italy), telemedicine was used in place of on-site follow-up visits scheduled but not provided during the COVID-19 pandemic: all IBD and CeD outpatients received a phone call, while video consultations were performed for patients with mild-to-moderate symptoms, with bio-umoral alterations or as needed for those patients who requested it. The patients’ trust in telemedicine was assessed through an adapted version of the PAtient Trust Assessment Tool (PATAT) questionnaire.¹³ The primary endpoint was expressed as a percentage >75% of patients giving a score of at least 4/5 on a Likert scale for three selected key statements about telemedicine.

Results

Two-hundred and ninety-eight patients were interviewed by phone, and 154/165 (93%) scheduled video consultations were performed. Among the 154 consultations, 134 (87%) questionnaires were compiled. The primary endpoint of trust in the telemedicine service was achieved in 93.4%, 87.5% and 85.3% of the respondents for the three selected key statements (trust the service, its capability to solve clinical problems and ease of use).

Conclusion

During the COVID-19 pandemic, our results showed that most of our IBD and CeD patients accepted and trusted video consultation as an alternative to the traditional in-person examination.

Disclosure: Nothing to disclose.

References

 1. American Telemedicine Association. Telehealth basic, https://www.americantelemed.org/resource/why-telemedicine/

 2. Wilson LS, Maeder AJ. Recent directions in telemedicine: review of trends in research and practice. Healthc Inform Res 2015; 21: 213–222.

 3. Ray Dorsey E, Topol EJ. State of telehealth. N Engl J Med 2016; 375: 154–161.

 4. Siniscalchi M, et al. COVID-19 pandemic perception in adults with celiac disease: an impulse to implement the use of telemedicine. Dig Liver Dis 2020; 52: 1071–1075.

 5. George LA, Cross RK. Remote monitoring and telemedicine in IBD: are we there yet? Curr Gastroenterol Rep 2020; 22: 12.

 6. Cross RK, et al. TELEmedicine for Patients with Inflammatory Bowel Disease (TELE-IBD): design and implementation of randomized clinical trial. Contemp Clin Trials 2015; 42: 132–144.

 7. De Jong MJ, et al. Cost-effectiveness of telemedicine-directed specialized vs. standard care for patients with inflammatory bowel diseases in a randomized trial. Clin Gastroenterol Hepatol 2020; 18: 1744–1752.

 8. Del Hoyo J, et al. A web-based telemanagement system for improving disease activity and quality of life in patients with complex inflammatory bowel disease: pilot randomized controlled trial. J Med Internet Res 2018; 20: e11602.

 9. Cross RK, et al. A randomized controlled trial for TELEmedicine for Patients with Inflammatory Bowel Disease (TELE-IBD). Am J Gastroenterol 2019; 114: 472–482.

10. Li SX. Delivering high value inflammatory bowel disease care through telemedicine visits. Inflamm Bowel Dis 2017; 1678–1681.

11. Lees CW, et al. Innovation in inflammatory bowel disease care during the COVID-19 pandemic: results of a global telemedicine survey by the International Organization for the Study of Inflammatory Bowel Disease. Gastroenterology 2020; 159: 805–808.e1.

12. Allocca M, et al. Maintaining the quality standards of care for inflammatory bowel disease patients during the COVID-19 pandemic. Clin Gastroenterol Hepatol 2020; 18: 1882–1883.

13. Velsen LV, et al. Measuring patient trust in telemedicine services: development of a survey instrument and its validation for an anticoagulation web-service. Int J Med Inform 2017; 97: 52–58.

LB27 Psychological morbidity among inflammatory bowel disease patients during COVID-19: A UK cohort study

R Luber, A Duff, P Pavlidis, S Ray, SH Anderson, J Mawdsley, MA Samaan, P Irving

Guy’s and St Thomas’s NHS Foundation Trust, Gastroenterology, London, UK

Contact e-mail address: raphaelluber@gmail.com

Introduction

Patients with chronic diseases are believed to be at increased risk of mental-health conditions during the COVID-19 pandemic. However, no studies thus far have assessed the mental health of such patients during the current or past pandemics.

Aims and methods: We aimed to assess the incidence of psychological morbidity in a cohort of inflammatory bowel disease (IBD) patients during the COVID-19 pandemic, and to explore its association with risk of severe COVID-19 based on British Society of Gastroenterology guidelines¹ and other factors. A survey including the Patient Health Questionnaire-9, General Anxiety Disorder-7 and Perceived Stress Scale tools for depression, anxiety and stress, respectively, was administered to a cohort of IBD patients from a tertiary centre in London, UK, in June 2020.

Results

A total of 274 patients completed the survey (57% completion rate), including 54 low risk, 152 moderate risk and 68 high risk for severe COVID-19. Moderate–severe depression was observed in 61 (22.5%) and moderate–severe anxiety in 49 (18%), while 39 (14%) had both diagnoses (Table). The mean (SD) stress score was 16.2 (7.4). There was no association between degree of severe COVID-19 risk and psychological morbidity. Flare symptoms and fatigue were associated with worse psychological morbidity across all measures, while accessibility of information regarding COVID-19 risk and reducing that risk was protective for depression (OR = 0.56 (0.33–0.94), p = 0.03), anxiety (OR = 0.62 (0.4–0.96), p = 0.03), and stress (standardized β-coefficient –0.15 (–0.28 to –0.03), p = 0.02). A total of 79 (30%) respondents were interested in receiving psychological support during the pandemic, while 200 (76%) expressed interest beyond the pandemic.

Abstract No: LB27.

Depression, Anxiety and Stress, Stratified by Risk Category

	All patients (N=274)	Low risk (N=52)	Moderate risk (N=151)	High risk (N=68)	Between-groups comparison p-value	p-Value for trend
PHQ-9 depression category
None, n (%)	118 (43.5)	24 (46.2)	70 (46.4)	24 (35.3)	0.56	0.06
Mild, n (%)	92 (33.9)	19 (36.5)	50 (33.1)	23 (33.8)
Moderate, n (%)	36 (13.3)	6 (11.5)	19 (12.6)	11 (16.2)
Moderately severe, n (%)	17 (6.3)	2 (3.8)	7 (4.6)	8 (11.8)
Severe, n (%)	8 (3.0)	1 (1.9)	5 (3.3)	2 (2.9)
GAD-7 anxiety category
None, n (%)	140 (51.9)	25 (48.1)	85 (56.3)	30 (44.8)	0.80	0.58
Mild, n (%)	81 (30)	17 (32.7)	42 (27.8)	22 (32.8)
Moderate, n (%)	25 (9.3)	5 (9.6)	12 (7.9)	8 (11.9)
Severe, n (%)	24 (8.9)	5 (9.6)	12 (7.9)	7 (10.4)
Perceived Stress Scale score
M (SD)	16.2 (7.4)	16.9 (7.7)	15.6 (7.3)	17 (7.6)	0.30	0.69

Conclusion

Depression, anxiety and stress among IBD patients during the pandemic are common. However, their frequency is similar to pre-pandemic rates and current general population levels. Ensuring easy access to personalized risk information with targeted psychological support may mitigate psychological burden as patients reintegrate into society and deal with future COVID-19 waves.

Disclosure: RPL has received educational grants from Ferring, Pfizer, Vifor Pharma. MAS served as a speaker, a consultant and/or an advisory board member for Sandoz, Janssen, Takeda, MSD, Falk, Samsung Bioepis. PMI has served as a speaker, a consultant and/or an advisory board member for Abbvie, Warner Chilcott, Ferring, Falk Pharma, Takeda, MSD, Johnson & Johnson, Shire, Vifor Pharma, Pharmacosmos, Topivert, Genentech, Hospira, Samsung Bioepis, and has received research funding from MSD, Takeda. AD, PP, SR, SHA and JM have no conflicts of interest to declare.

Reference

1. Kennedy NA, et al. British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic. Gut 2020; 69: 984–990.