IMPACT OF ETRASIMOD ON BLOOD PRESSURE AND HYPERTENSION: DATA FROM THE ETRASIMOD ULCERATIVE COLITIS CLINICAL PROGRAMME

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

Increased blood pressure (BP) and hypertension are known adverse effects of sphingosine 1-phosphate (S1P)_1,4,5 receptor modulators. Etrasimod is an investigational, oral, once-daily, selective S1P_1,4,5 receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC).

Aims & Methods

We assessed the impact of etrasimod on BP and hypertension development among patients (pts) in the etrasimod UC clinical programme. Pivotal (placebo [PBO]-controlled phase [p]3 [NCT03945188; NCT03996369] studies) and All UC (PBO-controlled plus open-label extension [OLE]; p2 [NCT02447302], p3 and OLE [NCT03950232 and NCT04176588, data snapshot Jan 31, 2022; NCT02536404] studies) cohort data were analysed. BP was assessed at each visit and at 2 and 4 weeks (wks) post‑treatment cessation. Proportions and exposure-adjusted incidence rates (EAIRs; pts with AEs divided by the total pt‑years [PY] at risk for AEs, per 1 PY) of treatment‑emergent Hypertension (Medical Dictionary for Regulatory Activities preferred term [PT]) AEs among pts receiving etrasimod (2 mg once daily; both cohorts) or PBO (Pivotal UC cohort) were assessed. Characteristics of pts with Hypertension AEs that met sponsor-designated events of interest (SDEI) criteria (related to hypertension associated with sustained increases in BP [systolic/diastolic: ≥ 160/100 mmHg], or requiring new or increased antihypertensive therapy) were analysed descriptively.

Results

In the Pivotal and All UC cohorts, 11/527 (2.1%; EAIR, 0.04; PBO: 2/260 [0.8%; EAIR, 0.02]) and 20/942 (2.1%; EAIR, 0.03) etrasimod-treated pts had PT Hypertension, respectively; none led to study treatment discontinuation. In the All UC cohort, 19/942 (2.0%; EAIR, 0.02) etrasimod-treated pts had hypertension-related SDEIs. Of these events, 6 were in pts with hypertension history; none were serious or led to treatment discontinuation; 6 resolved (5 with intervention), 8 were resolving/unknown outcome and 5 were unresolved. Etrasimod‑treated pts had minimal changes in BP over time (All UC cohort, mean change in systolic/diastolic BP at Wk52: 2.9/1.2 mmHg, respectively; Table). In the All UC cohort, at Wk104, no etrasimod-treated pts had a systolic/diastolic BP > 160/100 mmHg, respectively.

Table. Change from baseline in BP over time among pts in the etrasimod UC clinical programme (Pivotal and All UC cohorts)
Time point	Pivotal UC cohort				All UC cohort
	Systolic BP, mmHg		Diastolic BP, mmHg		Time point	Systolic BP, mmHg	Diastolic BP, mmHg
	Etrasimod 2 mg QD (N=527)	PBO (N=260)	Etrasimod 2 mg QD (N=527)	PBO (N=260)	Time point	Etrasimod 2 mg QD (N=942)
Baseline^a, mean (SD) [etrasimod, n=527; PBO, n=260]	120.7 (12.50)	121.3 (13.08)	75.8 (8.53)	77.2 (9.56)	Baseline^a, mean (SD) [n=942]	119.6 (12.89)	75.6 (8.57)
Change at Wk12, mean (SD) [etrasimod, n=474; PBO, n=231]	2.0 (11.17)	-1.4 (10.68)	1.6 (8.08)	-0.4 (8.07)	Change at Wk12, mean (SD) [n=821]	2.1 (10.78)	1.7 (8.01)
Change at Wk52, mean (SD) [etrasimod, n=162; PBO, n=44]	2.2 (11.08)	1.3 (9.16)	0.4 (8.47)	-0.8 (8.52)	Change at Wk52, mean (SD) [n=246]	2.9 (10.39)	1.2 (8.36)
Change at Wk78/ Wk104^b, mean (SD) [N/A]	-	-	-	-	Change at Wk78/ Wk104, mean (SD) [Wk78, n=147; Wk104, n=29]	1.9 (10.65)/ -0.7 (13.54)	1.1 (8.05)/ 0.8 (7.40)
Change at 2-/4-wk follow-up visit^c, mean (SD) [2‑wk: etrasimod, n=39; PBO, n=6; 4‑wk: etrasimod, n=36; PBO, n=10]	0.2 (10.66)/ -0.4 (11.47)	6.7 (10.61)/ 8.1 (8.18)	1.6 (7.99)/ 0.2 (10.40)	3.2 (3.71)/ 3.0 (7.12)	Change at 2-/4-wk follow-up visit^c, mean (SD) [2‑wk; n=203; 4‑wk, n=105]	2.6 (13.73)/ 1.9 (12.43)	1.3 (8.74)/ 1.4 (9.18)
Pivotal UC cohort comprised patients from the placebo-controlled p3 ELEVATE UC 52 (NCT03945188) and p3 ELEVATE UC 12 (NCT03996369) studies. All UC cohort comprised patients from the p2 OASIS (NCT02447302), p2 OASIS OLE (NCT02536404 [completed Nov 01, 2018]), p3 ELEVATE UC 52 (NCT03945188), p3 ELEVATE UC 12 (NCT03996369) and p3 ELEVATE UC OLE (NCT03950232 [data snapshot Jan 31, 2022]) studies, and the open-label phase of the p3 study NCT04176588 (data snapshot Jan 31, 2022) ^aBaseline is defined, by study treatment group received, as the last non-missing measurement taken on or prior to the study treatment group start date ^bWk78 and 104 data are not provided for the Pivotal UC cohort as only data up to Wk52 of ELEVATE UC 52 are included for pts in this cohort ^cPts who did not participate in the OLE study had 2-wk and 4-wk follow-up visits after their last treatment administration BP, blood pressure; N, total number of patients; n, number of patients with evaluable data at a visit; N/A, not applicable; OLE, open-label extension; p, phase; pts, patients; PBO, placebo; QD, once daily; SD, standard deviation; UC, ulcerative colitis; wk, week

Conclusion

Hypertension events were infrequent among etrasimod-treated pts. No clinically meaningful changes in BP with etrasimod 2 mg over time or following treatment discontinuation were observed up to 2 years. Data interpretations are limited by small pt numbers.

Disclosure

SV: lecture/speaker fees: AbbVie, Dr. Falk Pharma, Ferring Pharmaceuticals, Hospira, MSD, Takeda, Tillotts; consultancy/advisory fees: AbbVie, AbolerIS, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Dr. Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, Gilead Sciences, 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, Zealand Pharma; grant/research support: AbbVie, MSD, Pfizer Inc, Galapagos, Takeda.
DTR: grant support: Takeda, Helmsley Charitable Trust and GastroIntestinal Research Foundation; consultancy fees/advisory boards: AbbVie, AltruBio, ASLAN Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chronicles, Syneos, ClostraBio, Connect Biopharma, EcoR1, Genentech/Roche, Gilead Sciences, Iterative Health, Janssen Pharmaceuticals, Kaleido Biosciences, Eli Lilly, Pfizer, Prometheus, Reistone, Seres Therapeutics, Takeda, Target RWE, Trellus Health; Board of Trustees: Crohn’s & Colitis Foundation and Cornerstones Health, Inc; stock options: Alike Health, AltruBio, Datos Health, Iterative Health.
LP-B: grant/research support: Takeda, Fresenius Kabi, Celltrion; lecture/speaker fees: Galapagos, AbbVie, Janssen, Genentech, Ferring Pharmaceuticals, Tillotts, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena Pharmaceuticals, Lilly, Gilead Sciences, Viatris, Medac, Sanofi; consultancy fees: AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Biogen, Bristol-Myers Squibb, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, Gossamer Bio, GSK, 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, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, TiGenix, Tillotts, Viatris, Vifor, Ysopia, Abivax; stockholder: CTMA.
MCD: consultancy fees: AbbVie, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Genentech, Gilead Sciences, Janssen Pharmaceuticals, Pfizer Inc, Prometheus Laboratories, Takeda, Trellus Health, UCB; grant/research support: Janssen; shares/royalties: Trellus Health; directorship/ownership interests: Trellus Health.
MR: Unrestricted Educational Grants: Abbvie, BMS, Janssen, UCB, Pfizer, Takeda, Celgene, Genentech, Gilead; advisory boards/Consultant: Abbvie, Janssen, UCB, Takeda, Pfizer, Miraca Labs, Amgen, Celgene, Seres, Allergan, Genentech, Gilead, Salix, Prometheus, Lilly, TARGET Pharma Solutions, ALFASIGMA, S.p.A., Bristol-Myers Squibb (BMS), CME Companies: CME Outfitters, Imedex, GI Health Foundation (GiHF), Cornerstones, Remedy, MJH life sciences; royalties: Wolters Kluwer Health: Author/Editor of UpToDate.
PMI: grant support: Celltrion, Janssen, MSD, Takeda; lecture fees: AbbVie, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, MSD, Janssen, Pfizer, Takeda, Tillotts, Sapphire Medical, Sandoz, Shire, Warner Chilcott; advisory fees: AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Genentech, Gilead Sciences, Hospira, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Prometheus, Roche, Sandoz, Samsung Bioepis, Takeda, Topivert, VH2, Vifor, Warner Chilcott.
MG and KL: employees & shareholders of Pfizer AG.
JW, IM, JCW, CR: employees & shareholders of Pfizer Inc.
AM: employee of Pfizer Ltd and shareholder of Pfizer Inc.
AY: consultancy fees: Pfizer, Arena Pharmaceuticals, Takeda, Bristol-Myers Squibb; lecture/speaker fees: Bristol-Myers Squibb.

IMPACT OF ETRASIMOD ON BLOOD PRESSURE AND HYPERTENSION: DATA FROM THE ETRASIMOD ULCERATIVE COLITIS CLINICAL PROGRAMME

Severine Vermeire 1, David T. Rubin 2, Laurent Peyrin-Biroulet 3, Marla C. Dubinsky 4, Miguel Regueiro 5, Peter Irving 6, Martina Goetsch 7, Krisztina Lazin 7, Joseph Wu 8, Irene Modesto 9, John C. Woolcott 10, Aoibhinn McDonnell 11, Chris Rabbat 12, Andres Yarur 13

1 University Hospital Leuven, Leuven, Belgium

2 University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, United States

3 University of Lorraine, CHRU-Nancy, Nancy, France|||University of Lorraine, Inserm, NGERE, Nancy, France

4 Icahn School of Medicine at Mount Sinai, New York, United States

5 Cleveland Clinic, Cleveland, United States

6 Guy´s and St Thomas´ Hospital, London, United Kingdom

7 Pfizer AG, Zürich, Switzerland

8 Pfizer Inc, Groton, United States

9 Pfizer Inc, Madrid, Spain

10 Pfizer Inc, Collegeville, United States

11 Pfizer Ltd, Sandwich, Kent, United Kingdom

12 Pfizer Inc, New York, United States

13 Cedars-Sinai Medical Center, Los Angeles, United States

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

PP 05 IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

UEG's educational platform for gastroenterology education bringing recordings, courses, guidelines, and more together in one place.

Most popular content

Rate for better recommendations!

Introduction

Aims & Methods

Results

Conclusion

Disclosure

IMPACT OF ETRASIMOD ON BLOOD PRESSURE AND HYPERTENSION: DATA FROM THE ETRASIMOD ULCERATIVE COLITIS CLINICAL PROGRAMME

Conference

Submission format

Citation

Published

Optimising success in IBD treatment: Timing surgery and medical treatment

Event

Citation

Published

Optimising surgical therapies in fistulising Crohn's disease

Event

Citation

Published

The pregnant IBD patient (Complete Session)

Event

Citation

Published

Will there be pathologists in 2030 or only AI?

Event

Citation

Published

Fistulising Crohn's disease: Underlying mechanism

Event

Citation

Published

Managing IBD in a patient with new or recent cancer

Event

Citation

Published