Introduction

When conventional ulcerative colitis (UC) therapy fails to achieve or maintain remission, advanced UC therapies should be considered to improve patient outcomes. The responder re-randomisation trial (efficacy reported at the end of the maintenance phase for patients who achieved induction clinical response) is a common design used in UC drug development. Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active UC. The etrasimod ELEVATE UC 52 trial utilised a treat-through design, where efficacy at the end of the maintenance phase was reported for the total baseline population.

Aims & Methods

This post hoc analysis evaluated the efficacy of etrasimod vs placebo at Week 52 among biologic/Janus kinase inhibitor (bio/JAKi)-naïve patients with moderately to severely active UC who achieved clinical response at Week 12. ELEVATE UC 52 (NCT03945188) comprised a 12-week induction phase followed by a 40-week maintenance phase with a treat-through design. Patients were randomised 2:1 to receive etrasimod 2 mg or placebo QD. Week 12 clinical response was defined as a ≥2-point and ≥30% decrease from baseline in modified Mayo score (MMS), and a ≥1-point decrease or absolute value ≤1 in rectal bleeding subscore. Efficacy outcomes evaluated in Week 12 bio/JAKi-naïve responders (baseline MMS 5–9) were the achievement of clinical remission, clinical response, symptomatic remission, endoscopic improvement, endoscopic improvement-histologic remission and corticosteroid-free clinical remission at Week 52.

Results

Among bio/JAKi-naïve patients, Week 12 clinical response was achieved by 132/194 (68.0%) receiving etrasimod and 35/93 (37.6%) receiving placebo. Among Week 12 responders, significantly greater proportions receiving etrasimod vs placebo achieved clinical remission (51.5% vs 17.1%; p<0.001) and all secondary endpoints at Week 52 (all p<0.05; Table).

Conclusion

Etrasimod demonstrated significant efficacy over placebo in all Week 52 efficacy outcomes in bio/JAKi-naïve induction treatment responders. These findings help contextualize data from the ELEVATE UC clinical programme for patients receiving their first advanced UC therapy within a treat-through trial design.

References

Disclaimer: Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.

Disclosure

SV: Lecture/speaker/consultancy/advisory fees: AbbVie, AbolerIS Pharma, Alimentiv, Arena, AstraZeneca, Avaxia, Boehringer Ingelheim, BMS, Celgene, CVasThera, Dr Falk Pharma, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, J&J, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer Inc, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance Biopharma, Tillotts, Zealand Pharma.
Grant/research support: AbbVie, MSD, Galapagos, Janssen, Pfizer Inc, Takeda.
BES: Consultant/speaker fees: AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, BMS, Calibr, Celgene, Celltrion, ClostraBio, Enthera, Equillium, Evommune, Ferring, Fresenius Kabi, Fzata, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Janssen, Kaleido, Kallyope, Lilly, Merck, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Palisade Bio, Pfizer Inc, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Sun Pharma, Surrozen, Takeda, Target RWE, Teva, Theravance Biopharma, TLL Pharmaceutical, TR1X, Union Therapeutics, Ventyx Biosciences.
Stock and stock options: Ventyx Biopharma.
Research grants/other support: Abivax, BMS, Janssen, Lilly, Pfizer Inc, Takeda.
MCD: Consultant: AbbVie, Abivax, Arena Pharmaceuticals, AstraZeneca, BMS, Eli Lilly, Galapagos, Genentech, Gilead Sciences, Janssen Pharmaceuticals, J&J, Merck, Pfizer Inc, Prometheus Laboratories, Prometheus Biosciences, Sanofi, Sphyre, Takeda, UCB.
Shareholder/royalties/directorship/ownership interest: Trellus Health.
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 organization, which is owned by a medical trust.
Consultant/speaker/advisory board: 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/Roche, Gilead, Gossamer Pharma, GlaxoSmithKline, 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.
RP: Consultant/speaker/advisory board: Abbott, AbbVie, Abivax, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, BMS, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer Inc, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma, Trellus, Viatris, Ventyx, UCB.
Research support: AbbVie, Janssen, Takeda, Pfizer Inc.
VJ: Speaker/consultant/advisory board: AbbVie, Alimentiv Inc, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, BMS, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer Inc, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, SCOPE, Second Genome, Shire, Sorriso, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion.
AJY: Consultancy/lecture fees: AbbVie, Arena, BMS, Celltrion, Pfizer Inc, Takeda.
MVC: Grant support: BMS, J&J, Novartis, Pfizer Inc.
Consultant/speaker: AbbVie, Arena, BMS, Celltrion, Fresenius Kabi, J&J, Lilly, Medtronic, Pfizer Inc, Prometheus, Takeda.
AW: Grant/research support: AbbVie, Alfasigma, BMS, Buhlmann, Falk, Ferring, Galapagos, Janssen, Lilly, Pfizer Inc, Takeda.
MG: Employee: Pfizer AG; shareholder: Pfizer Inc.
JW/AMA/CC: Employees/shareholders: Pfizer Inc.
BS: Employee/shareholder: Pfizer Ltd.
SG: Steering/drug monitoring committee: AbbVie, BMS, Janssen.
Speaker/advisory board: AbbVie, BMS, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, Pfizer Inc, Takeda.
Financial support/grants: GlaxoSmithKline.

Introduction

Etrasimod (2 mg/day, oral) is a novel alternative for moderate-to-severe active ulcerative colitis (UC), which has proved to be effective in ELEVATE UC12 and UC52 trials^1,2.

Aims & Methods

This cost-effectiveness analysis compared etrasimod vs. most frequently used biologics in Spain³, for patients with moderate-to-severe active UC experienced to advanced therapies (AT), from the perspective of the Spanish national health system.
A hybrid model simulated the induction (decision tree) and maintenance (Markov model, 8-week cycles during lifetime) phases treatment to estimate costs (€, 2025) and quality-adjusted life years (QALYs), both yearly discounted (3%). All model inputs derived from scientific literature and were validated by national experts. The patients’ characteristics proceeded from etrasimod trials^1,2. Rates of efficacy, safety, and loss of response of etrasimod, adalimumab, ustekinumab, intravenous (IV) vedolizumab and subcutaneous (SC) vedolizumab were obtained from a Bayesian network meta-analysis^4,5.
After loss of response, a loop of subsequent AT in perpetuity was applied. Total costs included drugs acquisition (authorized posology and dose intensifications when required, both based on the European Public Assessment Reports [EPARs])^6,7, IV administration (€77.16)⁸, adverse events (€5,964.49 per serious infection)⁸ and management of UC (cost): active UC (€4,471)^9,10, response without remission (€1,801)^9,10, remission (€762)^9,10, surgery (€4,448)⁹, post-surgery without complications (€1,101)^9,10 and with complications (€6,428)^9,10. The annual surgery rate in UC was 0.34%¹⁰ (urgent: 38.2%; elective: 61.8%)¹¹, early and late complications occurred in 18.4%¹² and 46% (for 6.5 years)¹³. Utility values were 0.78 for active UC^1,2, 0.82 for response without remission^1,2, 0.89 for remission^1,2, 0.74 for surgery¹⁴, 0.90 for post-surgery without complications¹⁴ and 0.71 with complications¹⁴. Concomitant treatment with azathioprine (35% patients, biologics only), mercaptopurine (15% patients, biologics only), mesalazine (40% patients), prednisone (20% patients) and beclomethasone (10% patients) were considered^7,15. In addition to age and sex-specific mortality in Spain¹⁶, the excess mortality associated with colectomy was considered (relative risk: 1.3)¹⁷. A probabilistic sensitivity analysis (PSA) tested the results’ robustness.

Results

Etrasimod yielded more QALYs compared to each biologic and produced cost-savings in all pairwise comparisons except for IV vedolizumab (Table 1). Thus, etrasimod was cost-effective compared to IV vedolizumab (€16,212/QALY), and dominant compared with all remaining biologics. PSA revealed that etrasimod was dominant compared to each biologic (average of Monte Carlo simulations). Under a willingness to pay threshold of €27,000/QALY¹⁸, etrasimod was cost-effective in a minimum of 58.5% simulations (vs. IV vedolizumab) and a maximum of 99.9% (vs. adalimumab), varying between pairwise comparisons of etrasimod vs. biologic.

Conclusion

Etrasimod represents a cost-effective alternative for AT-experienced patients with moderate-to-severe active UC compared with biologics available in Spain.

References

¹ https://clinicaltrials.gov/study/NCT03945188; ² Sandborn WJ. Lancet. 2023;401:1159–71; ³ Gómez-Labrador C. Pharmaceutics. 2024;16:629; ⁴ Jaraith V. J Comp Eff Res. 2025:e240225; ⁵ https://scientificpubs.congressposter.com/p/k0b1nw0im7astcj2; ⁶ https://cima.aemps.es/cima/publico/home.html; ⁷ https://botplusweb.farmaceuticos.com/; ⁸ https://esalud.oblikue.com/; ⁹ Trigo-Vicente C. Expert Rev Pharmacoecon Outcomes Res. 2018;18:321–9; ¹⁰ Guasch M. Dig Liver Dis. 2021;53:54–60; ¹¹ Núñez L. Gastroenterol Hepatol. 2023;46:369–75; ¹² García MJ. J Clin Med. 2021;10:4402; ¹³ Ferrante M. Inflamm Bowel Dis. 2008;14:20–8; ¹⁴ Kosmas C. Value Health. 2015;18:A630; ¹⁵ https://www.nice.org.uk/guidance/ta828; ¹⁶ https://ine.es/dyngs/INEbase/es/operacion.htm?c=Estadistica_C&cid=1254736177004&menu=ultiDatos&idp=1254735573002; ¹⁷ Jess T. Am J Gastroenterol. 2007;102:609–17; ¹⁸ Vallejo-Torres L. PharmacoEconomics. 2025;43:109-22.

Disclosure

This work was sponsored by Pfizer®.
IRL, FMN, AJLV and EMB have received fees for their scientific advice and contribution to the publication.
AC and ALJ are employees of Pfizer SLU.
ACG and IO are employees of Pharmacoeconomics & Outcomes Research Iberia (PORIB), a consultant company specializing in health economics and outcomes research, which has received fees from Pfizer SLU for conducting the present study.
IRL has received financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Alfasigma, Biogen, Chiesi, Faes Farma, Ferring, Fresenius Kabi, Galapagos, Johnson & Johnson, Eli Lilly, Mirum Pharmaceuticals, Merck, Pfizer, Roche, Takeda, and Tillotts Pharma.

Introduction

Lower gastrointestinal bleeding (LGIB) is a frequent clinical challenge, particularly in elderly patients and those on anticoagulants. While anticoagulants are known to increase bleeding risk, their impact on LGIB outcomes remains uncertain.

Aims & Methods

To assess whether anticoagulant use is independently associated with adverse outcomes in patients hospitalized with acute LGIB, using robust propensity score-based methods to adjust for confounding.
Methods: This study was a post-hoc analysis of prospectively collected data from a multicenter, international cohort of 1911 patients hospitalized for LGIB. Propensity score matching (PSM) was performed using a logistic regression model, incorporating key covariates including demographics, comorbidities, comedications (antiplatelets, nonsteroidal anti-inflammatory drugs), prior history of LGIB, bleeding presentation (melena or hematochezia, hemodynamic instability) and care setting (inpatient vs. outpatient). Patients on anticoagulants were matched 1:1 with controls using nearest-neighbor matching (caliper=0.2). Covariate balance after adjustment was assessed using standardised mean differences (SMDs), with all variables achieving an SMD<0.2. Primary outcomes were in-hospital death and rebleeding. Secondary outcomes included red blood cell (RBC) transfusion and surgery. McNemar’s test was used for outcome comparisons between anticoagulant users and matched controls. Subgroups analysis to compare DOACs vs. VKAs was conducted using chi-squared and Mann–Whitney U tests, as appropriate.

Results

Among the original cohort of 1911 patients (mean age 77 years, IQR 66-84; 54.2% male), 610 (31.9%) were on anticoagulants (310 direct oral anticoagulant [DOACs], 188 vitamin K antagonists [VKAs], 89 low-molecular-weight or unfractionated heparin, and 23 unspecified). Overall, in-hospital death occurred in 72 (3.8%), rebleeding in 166 (8.7%), surgery in 104 (5.4%), and RBC transfusion in 836 (43.7%) patients. The matched cohort included 980 patients (490 per group). Anticoagulant use was not significantly associated with higher in-hospital mortality (OR 1.16, 95% CI 0.63-2.14), rebleeding (OR 1.42, 95% CI 0.90-2.25), or surgery (OR 0.75, 95% CI 0.43-1.32). However, it was related with higher RBC transfusion rates (OR 1.66, 95% CI 1.28-2.14). In the subgroup analysis, outcomes were comparable between DOACs and VKAs.

Conclusion

In patients hospitalized with LGIB, anticoagulant use is not associated with increased mortality, rebleeding, or surgical intervention but is linked to a higher need for RBC transfusion.

References

Oakland K., et al., Re-bleeding and Mortality After Lower Gastrointestinal Bleeding in Patients Taking Anti-platelets or Anti-coagulants, Clin Gastroenterol Hepatol, 2019
Radaelli F., et al., Clinical management and patient outcomes of acute lower gastrointestinal bleeding. A multicenter, prospective, cohort study, Dig Liver Dis, 2021
Dajti E., et al., In-hospital Mortality in Patients with Lower Gastrointestinal Bleeding: Development and Validation of a Prediction Score, Endoscopy, 2025

Disclosure

Emanuele Rondonotti and Franco Radaelli have received speaker honoraria from Fujifilm Co. The other authors have no disclosures.

Introduction

Previous studies reported a positive correlation between serum and tissue drug levels in IBD receiving intravenous (IV) infliximab (IFX) therapy, except in those with severely inflamed tissue (1). Tissue drug levels in patients with IBD receiving SC IFX have not yet been investigated. We aimed to compare both the serum and tissue drug levels between SC and IV IFX maintenance therapy in IBD patients.

Aims & Methods

Any IBD patients under maintenance therapy with SC or IV stable doses IFX who underwent a colonoscopy for routine follow-up were eligible. Patient and disease characteristics, as well as clinical and endoscopic activity were recorded. Clinical activity was defined by high activity score (CDAI or pMAYO score) with at least one elevated biomarker (fecal calprotectin >250 mg/g, serum CRP >5 mg/L). Endoscopic disease activity was categorized as absent (normal), low (mild inflammation), moderate (friability, aphthoid lesions), or severe (ulcerations), as reported by the endoscopist blinded to the results of serum and tissue drug levels. Two biopsies were taken from the same location (either the most active area or randomly if no endoscopic lesion), and tissue and serum IFX levels were measured simultaneously in a centralized manner blinded to clinical and endoscopic disease activity. Frozen biopsy specimens were treated with the Bio-Plex® Cell Lysis Kit after tissue cutting and homogenates were sonicated at 4°C (Omni Ruptor 205). Tissue extracts were then frozen at -80°C prior drug measurements (iTrack10; Theradiag).

Results

Thirty-five patients were enrolled (CD in 65%, Sex ratio 1.4, 14 % with clinically and 57 % with endoscopically active disease, and 23 under SC IFX therapy). The characteristics of both IV and SC IFX groups were comparable, except for drug dose intensification in 90% of those treated with IV IFX group and 5% in the SC IFX cohort (p < 0.001). In patient in endoscopic remission, tissue levels were undetectable or very low for both IV and SC IFX therapy. Serum and tissue drug levels were significantly higher in the SC IFX cohort compared with the IV IFX group (22 mg/mL vs 9 mg/mL for serum; p < 0.001 and 25 mg/g vs 10 mg/g for tissue; p = 0.002, respectively). A moderate correlation was found between serum and tissue drug levels for both IV and SC IFX therapy (Spearman r = 0.42; p = 0.014 and r = 0.43; p = 0.001, respectively). Tissue drug levels increased gradually in patients with minimal or moderate endoscopic activity and were lower in those with severe endoscopic activity for both IV and SC IFX groups (p < 0.001). Tissue drug levels remained significantly higher in minimal or moderate endoscopically active disease in SC compared with IV route of IFX administration. The two independent factors associated with drug tissue levels > 14 mg/g (median levels) were the SC IFX route (OR: 2.25, 95% CI = [1.19–2.23]; p = 0.001) and the serum IFX levels (OR: 1.63, 95% CI = [1.19–2.23]; p = 0.002). A serum IFX level greater than 16.1 mg/mL was highly predictive of a tissue drug level > 14 mg/g tissue (Se: 0.94, Spe: 0.94, PPV: 0.94, NPV: 0.94, and Accuracy = 94.3%).

Conclusion

Serum and tissue drug levels are positively correlated in IBD patients under IV and SC maintenance IFX therapy. Interestingly, drug levels were higher both in serum and tissue in patients under SC IFX compared with IV IFX and tissue drug levels gradually increased in minimally to moderately inflamed intestine but were lower or undetectable in more severe inflamed areas.

References

1. Yarur AJ, et al. The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: the ATLAS study. Gut 2016; 65: 249-255.