OPTIMAL DOSING OF SUBCUTANEOUS ADMINISTERED INFLIXIMAB DURING SWITCH AND START IN ADULTS AND CHILDREN WITH INFLAMMATORY BOWEL DISEASE: A SIMULATION STUDY

UEG Poster

Standard Poster

Log in to access this content.

Free for all myUEG account holders. Your access level is set automatically based on your occupation. Medical professionals get full access to all content. If you are a non-medical user, you can only access UEG Week content from congresses you attended.

Log In Create a free account

Not sure what you can access? Learn more about account types.

Introduction

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 ulcerative colitis (UC). Early patient (pt)-reported response is often seen as an indicator of continued improvement through Week (Wk) 12.¹

Aims & Methods

This post hoc analysis investigated relationships between pt-reported symptoms by Day 7 and clinical endpoints at Wk 12 in pts receiving etrasimod 2 mg QD or placebo in the ELEVATE UC clinical programme (NCT03945188, NCT03996369) using rectal bleeding (RB) and stool frequency (SF) subscores reported via daily e-diary records. For pts reporting symptomatic, RB and SF response by Day 7 (yes/no), the proportion achieving clinical endpoints (clinical remission [CR], endoscopic improvement [EI] and EI-histologic remission [EIHR]) at Wk 12 was measured. Adjusted risk differences in proportions of responders between treatment groups were estimated and tested using the Mantel-Haenszel weighted method.

Results

Among pts reporting symptomatic response by Day 7 (etrasimod 2 mg, N1 = 151; placebo, N1 = 60), pts treated with etrasimod vs placebo demonstrated significantly greater CR (47.7% vs 15.0%, adjusted difference [Δ] 33.9, p < 0.001), EI (54.3% vs 20.0%, Δ 35.7, p < 0.001) and EIHR (31.1% vs 6.7%, Δ 24.8, p < 0.001) rates at Wk 12 (Table). In pts who did not demonstrate symptomatic response by Day 7 (etrasimod 2 mg, N1 = 376; placebo, N1 = 200), those treated with etrasimod vs placebo achieved significantly greater rates of CR (18.9% vs 10.0%, Δ 8.7, p = 0.002), EI (27.7% vs 17.0%, Δ 10.5, p = 0.002) and EIHR (16.0% vs 7.5%, Δ 8.3, p = 0.002) at Wk 12 (Table). Similarly, Day 7 RB and SF responders and nonresponders treated with etrasimod vs placebo also demonstrated significantly greater rates of CR, EI and EIHR at Wk 12 (all p < 0.001; Table).

Table. Wk 12 clinical endpoint in Day 7 symptomatic, RB and SF responders and nonresponders (FAS with baseline MMS 4–9)
Data are pooled from ELEVATE UC 52 and ELEVATE UC 12. ^aDefined as SF subscore = 0 (or = 1 with a ≥ 1-point decrease from baseline), RB subscore = 0 and endoscopic subscore ≤ 1 (excluding friability). SF and RB subscores are derived from pt daily e-diary records using the scores from the three most recent consecutive days within the seven days prior to the day of bowel preparation, averaged and rounded to the nearest integer. ^bDefined as endoscopic subscore ≤ 1. ^cDefined as endoscopic subscore ≤ 1 with histologic remission measured by a Geboes Index score < 2.0. ^dDefined as pts achieving ≥ 30% decrease from baseline in partial MMS by Day 7. ^eDifference (%) is based on estimated common risk difference using the Mantel–Haenszel weights and is stratified by actual naïve to biologic/Janus kinase inhibitor therapy at study entry (yes/no), actual baseline corticosteroid use (yes/no) and actual baseline disease activity (MMS: 4–6 or 7–9). ^fThe 2-sided p value is to test the hypothesis of the common risk difference being 0 using Mantel–Haenszel weighted test. ^gDefined as pts achieving RB subscore ≥ 1-point decrease from baseline by Day 7, based on collected daily scores. ^hDefined as pts achieving SF subscore = 0 or ≥ 1-point decrease from baseline by Day 7, based on collected daily scores. Δ, adjusted difference; CI, confidence interval; CR, clinical remission; EI, endoscopic improvement; EIHR, EI-histologic remission; FAS, full analysis set; MMS, modified Mayo score; N, number of pts in treatment group; n, number of pts achieving Day 7 and Wk 12 endpoint; N1, number of pts achieving Day 7 endpoint; pt, patient; QD, once daily; RB, rectal bleeding; SF, stool frequency; UC, ulcerative colitis; Wk, Week.
	Clinical response^a at Wk 12, yes		Endoscopic improvement^b at Wk 12, yes		Endoscopic improvement histologic remission^c at Wk 12, yes
	Placebo QD (N = 260)	Etrasimod 2 mg QD (N = 527)	Placebo QD (N = 260)	Etrasimod 2 mg QD (N = 527)	Placebo QD (N = 260)	Etrasimod 2 mg QD (N = 527)
Day 7 symptomatic responder,^d n/N1 (%) Δ (95% CI)^e p value^f	9/60 (15.0)	72/151 (47.7) 33.9 (22.1, 45.7) < 0.001	12/60 (20.0)	82/151 (54.3) 35.7 (23.2, 48.3) < 0.001	4/60 (6.7)	47/151 (31.1) 24.8 (14.9, 34.7) < 0.001
Day 7 symptomatic nonresponder, n/N1 (%) Δ (95% CI)^e p value^f	20/200 (10.0)	71/376 (18.9) 8.7 (3.1, 14.3) 0.002	34/200 (17.0)	104/376 (27.7) 10.5 (3.8, 17.2) 0.002	15/200 (7.5)	60/376 (16.0) 8.3 (3.2, 13.4) 0.002
Day 7 RB responder,^gn/N1 (%) Δ (95% CI)^e p value^f	8/78 (10.3)	64/168 (38.1) 28.1 (18.0, 38.2) < 0.001	15/78 (19.2)	75/168 (44.6) 27.2 (15.9, 38.4) < 0.001	8/78 (10.3)	44/168 (26.2) 16.5 (6.9, 26.1) < 0.001
Day 7 RB nonresponder,n/N1 (%) Δ (95% CI)^e p value^f	21/182 (11.5)	79/359 (22.0) 10.7 (4.5, 16.9) < 0.001	31/182 (17.0)	111/359 (30.9) 14.1 (7.0, 21.2) < 0.001	11/182 (6.0)	63/359 (17.5) 11.7 (6.5, 17.0) < 0.001
Day 7 SF responder,^h n/N1 (%) Δ (95% CI)^e p value^f	6/46 (13.0)	55/114 (48.2) 34.7 (21.9, 47.6) < 0.001	10/46 (21.7)	65/114 (57.0) 34.2 (19.7, 48.8) < 0.001	3/46 (6.5)	34/114 (29.8) 22.5 (11.5, 33.6) < 0.001
Day 7 SF nonresponder, n/N1 (%) Δ (95% CI)^e p value^f	23/214 (10.7)	88/413 (21.3) 10.5 (4.9, 16.2) < 0.001	36/214 (16.8)	121/413 (29.3) 12.8 (6.3, 19.4) < 0.001	16/214 (7.5)	73/413 (17.7) 10.6 (5.5, 15.6) < 0.001

Conclusion

Pts treated with etrasimod may experience rapid symptomatic improvements. In ELEVATE UC, pts treated with etrasimod who both did and did not demonstrate rapid symptomatic improvements had higher rates of clinical endpoint achievement at Wk 12 vs placebo. Pts treated with etrasimod who demonstrated an early, Day 7 response had the greatest likelihood of meeting clinical endpoints at Wk 12.

References

1. Chaparro M et al. J Crohns Colitis 2023; 17: i107–i110.
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

MCD reports consulting fees from AbbVie, Abivax, Arena Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Galapagos, Genentech, Gilead Sciences, Janssen Pharmaceuticals, Johnson & Johnson, Merck, Pfizer Inc, Prometheus Laboratories, Prometheus Biosciences, Sanofi, Sphyre, Takeda and UCB; is a shareholder/receives royalties from Trellus Health, and has a directorship/ownership interest in Trellus Health.
MC receives speaker/consulting fees and research/education funding from AbbVie, Biogen, Dr. Falk Pharma, Ferring, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer Inc, Shire Pharmaceuticals, Takeda and Tillotts Pharma.
PMI receives grants from Celltrion, Janssen, MSD and Takeda; lecture fees from AbbVie, Bristol Myers Squibb, Celgene, Celltrion, Falk Pharma, Ferring, Galapagos, Gilead, MSD, Janssen, Pfizer Inc, Takeda, Tillotts, Sapphire Medical, Sandoz, Shire and Warner Chilcott; and advisory fees from AbbVie, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Genentech, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer Inc, Pharmacosmos, Prometheus, Roche, Sandoz, Samsung Bioepis, Takeda, Topivert, VH2, Vifor Pharma and Warner Chilcott.
PH is an employee of Pfizer Inc, a shareholder of Clene Nanomedicine, Haleon, Idorsia, Liquidia, Longboard Pharmaceuticals, Pfizer Inc and Proctor & Gamble; holds IP/patents for US 2022/0257594 A1; and receives grant/research support from AbbVie, Bristol Myers Squibb, Buhlmann, Janssen, Lilly, Pfizer Inc and Takeda.
SS, JCW, and WW are employees and shareholders of Pfizer Inc.
MG is an employee of Pfizer AG and shareholder of Pfizer Inc.
JT receives advisory board fees from AbbVie, Lilly, Janssen and Pfizer Inc; research grants from AbbVie and Janssen; and speaker fees from AbbVie, Janssen, Lilly, Takeda and Pfizer Inc.
RP receives consulting fees from Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, 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 Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx and UCB; speaker's fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer Inc, Roche, Sandoz, Shire and Takeda Pharmaceuticals; advisory board fees from AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer Inc, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals and Ventyx; and grant/research support from AbbVie, Janssen, Takeda and Pfizer Inc.

EARLY SYMPTOMATIC IMPROVEMENT ASSOCIATIONS WITH WEEK 12 OUTCOMES: E-DIARY RESULTS FROM THE ETRASIMOD ELEVATE UC CLINICAL PROGRAMME

Marla C. Dubinsky 1, María Chaparro 2, Peter Irving 3, Peter Hur 4, Sarah Sidhu 4, John C. Woolcott 5, Wenjin Wang 5, Martina Goestch 6, Joana Torres 7, Remo Panaccione 8

1 Susan and Leonard Feinstein IBD Center, Icahn School of Medicine at Mount Sinai, New York City, NY, United States

2 Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain

3 IBD Unit, Guy’s and St Thomas’ Hospital, London, United Kingdom

4 Pfizer Inc, New York, NY, United States

5 Pfizer Inc, Collegeville, PA, United States

6 Pfizer AG, Zürich, Switzerland

7 Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal|||Division of Gastroenterology, Hospital da Luz, Lisbon, Portugal

8 Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, AB, Canada

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

Assessing the effectiveness of IBD treatments: From clinical studies to real-world experience (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Poster

Standard Poster

Log in to access this content.

Free for all myUEG account holders. Your access level is set automatically based on your occupation. Medical professionals get full access to all content. If you are a non-medical user, you can only access UEG Week content from congresses you attended.

Log In Create a free account

Not sure what you can access? Learn more about account types.

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)^9,10and 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.

Table 1. Results of the cost-effectiveness analysis in AT-experienced patients with moderate-to-severe active UC.
AT: Advanced Therapy; ICER: Incremental Cost-Effectiveness Ratio; IV: Intravenous; PSA: Probabilistic Sensitivity Analysis; QALY: Quality-Adjusted Life Year; SC: Subcutaneous; WTP: Willingness-To-Pay; UC: Ulcerative Colitis. ^A Etrasimod represents a dominant alternative (yields more QALYs and cost-savings). ^B Etrasimod represents a cost-effective alternative when considering a WTP threshold of €27,000/QALY¹⁸.
	Etrasimod	Adalimumab	Adalimumab (biosimilar)	Ustekinumab	Vedolizumab (IV)	Vedolizumab (SC)
QALYs / Total costs [€]	18.407 / €596,254	18.394 / €613,994	18,394 / €610,273	18.388 / €632,484	18.240 / €593,559	18.236 / €619,896
Δ QALYs / Δ Costs [€] (Etrasimod vs. comparator)	–	+0.013 / -€17,740	+0.013 / -€14,019	+0.018 / -€36,230	+0.166 / +€2,695	+0.171 / -€23,642
ICER [€/QALY] (Etrasimod vs. comparator)	–	Etrasimod dominant ^A	Etrasimod dominant ^A	Etrasimod dominant ^A	€16,212 ^B	Etrasimod dominant ^A
PSA mean Δ QALYs / Δ Costs [€] (Etrasimod vs. comparator)		+0.061 / -€23,675	+0.061 / -€17,493	+0.075 / -€48,952	+0.154 / -€22,292	+0.140 / -€70,902
PSA mean ICER [€/QALY] (Etrasimod vs. comparator)	–	Etrasimod dominant ^A	Etrasimod dominant ^A	Etrasimod dominant ^A	Etrasimod dominant ^A	Etrasimod dominant ^A
Proportion of simulations cost-effective (WTP = €27,000/QALY)¹⁸(Etrasimod vs. comparator)	–	96.7%	88.9%	99.9%	58.5%	88.9%

Conclusion

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

References

¹https://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.

COST-EFFECTIVENESS ANALYSIS OF ETRASIMOD COMPARED WITH BIOLOGIC THERAPIES FOR PATIENTS WITH MODERATE-TO-SEVERE ACTIVE ULCERATIVE COLITIS EXPERIENCED TO PREVIOUS ADVANCED THERAPIES IN SPAIN

Iago Rodríguez-Lago 1, Jose Fernando Muñoz Nuñez 2, Alfredo J. Lucendo 3, Alfonso De Lossada Juste 4, Ana Cabez 4, Alberto de la Cuadra-Grande 5, Itziar Oyagüez 5, Emilio Monte-Boquet 6

1 Hospital Universitario de Galdakao, Bilbao, Spain

2 University Hospital of Salamanca, Salamanca, Spain

3 Hospital General de Tomelloso, Tomelloso, Spain

4 Pfizer SLU, Madrid, Spain

5 Pharmacoeconomics & Outcomes Research Iberia (PORIB), Pozuelo de Alarcón, Spain

6 Hospital Universitari i Politècnic La Fe, Valencia, Spain