Introduction

Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC), with demonstrated efficacy in patients (pts) with baseline modified Mayo Score (MMS) 4–9.¹ No prior clinical trials of advanced therapies in UC have studied efficacy only in pts with baseline MMS ≤6.

Aims & Methods

GLADIATOR (NCT04607837) was a proof-of-concept, global, randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of etrasimod in adults with mildly to moderately active UC (MMS 4–6; endoscopic subscore ≥2; rectal bleeding subscore ≥1) and inadequate response, loss of response or intolerance to ≥1 UC therapy. Pts were randomised 2:1 to etrasimod 2 mg or placebo once daily, stratified by previous biologic/Janus kinase inhibitor exposure and baseline corticosteroid use. GLADIATOR used a treat-through design (12-week [wk] induction period followed by a 40‑wk maintenance period). From Wk 12, pts whose disease had worsened or not improved vs baseline may have been eligible to enrol in an open-label extension trial (NCT03950232). The primary efficacy endpoint was the proportion of pts achieving clinical remission at Wk 52; additional endpoints are shown in the Table. Safety was monitored throughout the study.

Results

In the primary analysis set for efficacy, 127 and 60 pts received etrasimod and placebo, respectively. At Wk 52, 26.0% and 18.3% of pts receiving etrasimod and placebo, respectively, were in clinical remission (p=0.2524; Table). At Wk 12, a greater proportion of pts receiving etrasimod achieved clinical remission, endoscopic improvement (EI) and endoscopic improvement-histologic remission (EIHR) vs placebo (p<0.05; Table). Pts receiving etrasimod were more likely to achieve sustained clinical remission vs placebo (p=0.0104; Table). Etrasimod was generally well tolerated and findings were consistent with the known safety profile.

Conclusion

In pts with mildly to moderately active UC, etrasimod demonstrated higher rates of clinical remission, EI and EIHR at Wk 12, as well as sustained clinical remission at Wk 52, vs placebo. However, the primary endpoint of clinical remission at Wk 52 was not met. Etrasimod demonstrated efficacy in pts with UC with an MMS 4–9, including those with an MMS 4–6, in the ELEVATE UC clinical programme.¹ The proof-of-concept GLADIATOR trial further supports etrasimod’s efficacy in active UC and provides important insights on studying pts with mildly to moderately active UC.

References

1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171.

Disclosure

SD: Lecture fees: AbbVie, Amgen, Ferring Pharmaceuticals Inc, Gilead, Janssen, Mylan, Pfizer Inc, Takeda; Consultancy fees: AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Gilead Sciences, Hospira, Janssen, Johnson&Johnson, MSD, Mundipharma, Pfizer Inc, Roche, Sandoz, Takeda, TiGenix, UCB, Vifor; Directorship: Gastroenterology and Endoscopy.
MG, KL: Employees of Pfizer AG; shareholders of Pfizer Inc.
LPB: Consultancy fees: AbbVie, Abivax, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GlaxoSmithKline, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer Inc, Prometheus, Protagonist, Roche, Roivant, Samsung, Sandoz, Sanofi, Takeda, Theravance, Thermo Fisher, Tigenix, Tillotts, Viatris, Vifor, Vectivbio, Ventyx, Ysopia; Grants: Takeda, Fresenius Kabi, Celltrion; Lectures: AbbVie, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Genetech, Gilead, Janssen, Lilly, Medac, MSD, Pfizer Inc, Sandoz, Takeda, Tillotts, Viatris, Vifor.
AJY: Consultancy fees: AbbVie, Arena, BMS, Celltrion, Pfizer Inc, Takeda; Lectures: AbbVie, BMS.
MCD: Consultancy fees: AbbVie, Abivax, Arena Pharmaceuticals, AstraZeneca, BMS, Eli Lilly, Galapagos, Genentech, Gilead Sciences, Janssen Pharmaceuticals, Johnson&Johnson, Merck, Pfizer Inc, Prometheus Laboratories, Prometheus Biosciences, Sanofi, Sphyre, Takeda, UCB; Shareholder: Trellus Health; Directorship: Trellus Health.
DTR: Consultancy fees: AbbVie, Abivax SA, Altrubio, Avalo Therapeutics, Bausch Health, Bristol Myers Squibb, Buhlmann Diagnostics Corp, Celltrion, ClostraBio, Connect BioPharma, Douglas Pharmaceuticals, Eli Lilly & Co., Foresee, Genentech, Image Analysis Group, InDex Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Odyssey Therapeutics, Pfizer Inc, Sanofi, Takeda Pharmaceuticals, Throne, Vedanta; Grants: Takeda.
BGF: Senior Scientific Director of Alimentiv Inc, which provides central reading services. He is not a company employee and has no equity stake in the organisation, which is owned by a medical trust; Speaker fees: AbbVie, Janssen, Takeda; Consultancy fees: AbbVie, AbolerIS, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport Inc, Arena Pharma, Avoro Capital Advisors, Atomwise, BioJamp, Biora Therapeutics, Boehringer Ingelheim, Boxer, Celsius Therapeutics,Celgene/BMS, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech, Gilead, Gossamer Pharma, GSK, Hinge Bio, Hot Spot Therapeutics, Index Pharma, Imhotex, Immunic Therapeutics, JAKAcademy, Janssen, Japan Tobacco Inc, Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer Inc, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc, Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx Biosciences, VHSquared Ltd, Viatris, Ysios, Ysopia, Zealand Pharma; Shareholder: Gossamer Pharma.
GRDH: Advisory fees: AbbVie, AstraZeneca, Alimentiv, BMS, Boehringer Ingelheim, Celltrion, Cosmo, Eli Lilly, Galapagos, GSK, Johnson&Johnson, Takeda, Pfizer Inc, Polpharma, Prometheus Biosciences, Tillotts, Ventyx; Speaker fees: AbbVie, Boehringer Ingelheim, Celltrion, Eli Lilly, Johnson&Johnson, Takeda, Pfizer Inc, Tillotts.
FB: Research/grants: AbbVie, Amgen, Eurogenerics, Janssen, Takeda; Lectures: AbbVie, Arena Pharmaceuticals, Celltrion, Ferring, Galapagos, Janssen, Merck Sharp & Dohme, Pfizer Inc, Takeda; Consultancy fees: AbbVie, Abivax, Amgen, Arena Pharmaceuticals, Celgene, Celltrion, Ferring, Fresenius Kabi, Janssen, Merck Sharp & Dohme, Pfizer Inc, Sandoz.
GG, JY, NL, CZ, WW, SM, EHL, IM, SS, WN: Employees/shareholders of Pfizer Inc.
SV: Lectures: AbbVie, Dr. Falk Pharma, Ferring, Galapagos, Hospira, Janssen, MSD, Takeda, Tillotts; Consultancy fees: AbbVie, AbolerIS Pharma, Alimentiv, Arena, AstraZeneca, Avaxia, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Dr Falk Pharma, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, Johnson&Johnson, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer Inc, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance Biopharma, Tillotts Pharma AG, Zealand Pharma; Grants: AbbVie, MSD, Pfizer Inc, Galapagos, Janssen, Takeda.

Introduction

Capsule endoscopy (CE) is a minimally invasive and essential tool for assessing small bowel disorders, especially Crohn’s disease. Accurate detection of ulcers and erosions is vital for evaluating disease activity, guiding treatment, and monitoring therapeutic response. Although CE has revolutionized lesion detection, its manual interpretation remains time-consuming and subject to interobserver variability. Recent advances in artificial intelligence (AI), particularly convolutional neural networks (CNNs), offer promising solutions by enhancing diagnostic accuracy, reducing variability, and improving workflow efficiency. This study aimed to develop and validate a robust AI model capable of detecting and distinguishing small bowel ulcers and erosions across multiple CE platforms and clinical centers.

Aims & Methods

In a prospective, multicenter study conducted between January 2021 and April 2024, data were collected from centers in Portugal, Spain, and the United States. Two CE devices—PillCamSB3 and Olympus EC-10—were used to analyze 137 anonymized exams. The AI-assisted readings generated by a deep learning model were compared to standard-of-care (SoC) interpretations, with an expert consensus panel serving as the reference standard. Performance metrics included sensitivity, specificity, positive and negative predictive values (PPV, NPV), and area under the receiver operating characteristic curve (AUROC).

Results

Expert consensus identified ulcers and erosions in 56 patients (40.9%). Compared to the reference standard, SoC readings achieved 60.7% sensitivity, 98.8% specificity, 97.1% PPV, 78.4% NPV, and 83.2% accuracy. In contrast, the AI-assisted model achieved 94.6% sensitivity, 80.2% specificity, 76.8% PPV, 95.6% NPV, and 86.1% accuracy. The AI model was found to be both non-inferior (p < 0.001) and statistically superior (p < 0.001) to SoC. Notably, it identified 68 lesions, nearly double those detected by SoC (35), and demonstrated consistent performance across devices and centers. The mean AI-assisted reading time was 239 seconds (SD 138 seconds) per exam.

Conclusion

The AI-assisted model significantly outperformed conventional SoC in the detection of small bowel ulcers and erosions, achieving higher sensitivity and overall accuracy while substantially reducing reading time. This is the first multicenter validation of an interoperable AI solution for CE, capable of high diagnostic performance across different devices and clinical environments. These findings highlight the potential of AI to transform endoscopic evaluation and management in inflammatory bowel disease.