Non-serious adverse events in patients with ulcerative colitis receiving etrasimod: an analysis of the phase II OASIS and phase III ELEVATE UC 52 and ELEVATE UC 12 clinical trials

Charlie W Lees; Joana Torres; Yvette Leung; Séverine Vermeire; Marc Fellmann; Irene Modesto; Aoibhinn McDonnell; Krisztina Lazin; Michael Keating; Martina Goetsch; Joseph Wu; Edward V Loftus Jr

doi:10.1177/17562848241293643

Non-serious adverse events in patients with ulcerative colitis receiving etrasimod: an analysis of the phase II OASIS and phase III ELEVATE UC 52 and ELEVATE UC 12 clinical trials

Therap Adv Gastroenterol. 2024 Nov 7:17:17562848241293643. doi: 10.1177/17562848241293643. eCollection 2024.

Authors

Charlie W Lees^{1

2}, Joana Torres^{3

4

5}, Yvette Leung⁶, Séverine Vermeire⁷, Marc Fellmann⁸, Irene Modesto⁹, Aoibhinn McDonnell¹⁰, Krisztina Lazin¹¹, Michael Keating⁹, Martina Goetsch¹¹, Joseph Wu¹², Edward V Loftus Jr¹³

Affiliations

¹ Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
² Edinburgh IBD Unit, Western General Hospital, NHS Lothian, Edinburgh, UK.
³ Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal.
⁴ Division of Gastroenterology, Hospital da Luz, Lisbon, Portugal.
⁵ Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
⁶ Department of Medicine, Department of Gastroenterology, University of British Columbia, Vancouver, BC, Canada.
⁷ Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
⁸ Pfizer Switzerland AG, Schärenmoosstrasse 99, 8052 Zürich, Switzerland.
⁹ Pfizer Inc., New York, NY, USA.
¹⁰ Pfizer Ltd, Sandwich, UK.
¹¹ Pfizer AG, Zürich, Switzerland.
¹² Pfizer Inc., Cambridge, MA, USA.
¹³ Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

Abstract

Background: 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). It is known that non-serious treatment-emergent adverse events (TEAEs) may not lead to UC drug discontinuation but can affect treatment tolerability.

Objectives: This post hoc analysis evaluated the incidence of specific, common, non-serious TEAEs reported in the etrasimod UC clinical programme and the characteristics of affected patients.

Design: Data included patients from the Placebo-controlled UC cohort (phase II OASIS, and phase III ELEVATE UC 52 and ELEVATE UC 12 trials) receiving QD etrasimod (2 or 1 mg) or placebo.

Methods: Proportions and incidence rates (IRs; the number of patients with a TEAE divided by the total exposure in patient-years (PYs), per 100 PY) of Headache, Pyrexia, Nausea and Dizziness TEAEs were reported. Changes in heart rate among patients with Dizziness TEAEs were also evaluated.

Results: Among 943 patients (etrasimod 2 mg, N = 577 (276.7 PY); etrasimod 1 mg, N = 52 (11.4 PY); placebo, N = 314 (115.1 PY)), 48, 34, 27 and 21 patients experienced events of Headache, Pyrexia, Nausea and Dizziness, respectively. All events were non-serious; one patient treated with etrasimod was discontinued due to a Pyrexia TEAE. Numerically, IRs of Headache and Dizziness TEAEs were higher, and Nausea slightly higher, with etrasimod versus placebo (13.45 vs 8.63 per 100 PY, 6.52 vs 1.69 and 7.18 vs 5.13 per 100 PY, respectively); IRs were similar for Pyrexia. The duration of most TEAEs was 1-10 days.

Conclusion: In the etrasimod UC clinical programme, all Headache, Pyrexia, Nausea and Dizziness events were non-serious. Headache and Dizziness were more frequent, and Nausea slightly more frequent, among patients receiving etrasimod versus placebo. The post hoc nature of this analysis is a limitation. These results reiterate the favourable safety profile and tolerability of etrasimod.

Trial registration: ClinicalTrials.gov: NCT02447302; NCT03945188; NCT03996369.

Keywords: adverse event; dizziness; etrasimod; headache; nausea; pyrexia, sphingosine 1-phosphate; ulcerative colitis.

Associated data

ClinicalTrials.gov/NCT03945188
ClinicalTrials.gov/NCT02447302
ClinicalTrials.gov/NCT03996369