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. 2024 Nov 7:17:17562848241293643.
doi: 10.1177/17562848241293643. eCollection 2024.

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  1   2 , Joana Torres  3   4   5 , Yvette Leung  6 , Séverine Vermeire  7 , Marc Fellmann  8 , Irene Modesto  9 , Aoibhinn McDonnell  10 , Krisztina Lazin  11 , Michael Keating  9 , Martina Goetsch  11 , Joseph Wu  12 , Edward V Loftus Jr  13
Affiliations

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 et al. Therap Adv Gastroenterol. .

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.

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Conflict of interest statement

C.W.L. has received speaker fees from AbbVie, Dr Falk, Ferring, Hospira, Janssen, MSD, Pfizer Inc., Shire, Takeda and Warner-Chilcott; has receiving consultant fees from AbbVie, Dr Falk, Gilead, GSK, Hospira, Iterative Scopes, Janssen, MSD, Oshi Health, Pfizer Inc., Pharmacosmos, Takeda, Topivert, Trellus Health and Vifor Pharma and has received research funding from AbbVie and Gilead. J.T. has received advisory board fees from AbbVie, Bristol-Myers Squibb, Janssen and Pfizer Inc.; has received research grants from AbbVie and Janssen and has received speaker fees from AbbVie, Galapagos, Janssen and Pfizer Inc. Y.L. has served on advisory committee/as a board member for AbbVie, Celltrion, Eli Lilly, Janssen, Pfizer Inc., Sandoz, Takeda and has acted as a consultant for AbbVie, Eli Lilly, Janssen, Pfizer Inc. and Takeda. S.V. has received research grants from AbbVie, Galapagos, J&J, Pfizer and Takeda and has received speakers’ and/or consultancy fees from AbbVie, Abivax, AbolerISPharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, Mestag Therapeutics, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer Inc., Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Surrozen, Takeda, Theravance, Tillotts Pharma AG, VectivBio, Ventyx and Zealand Pharma. M.F., I.M., A.M., K.L., M.K. and J.W. are employees and shareholders of Pfizer Inc. M.G. is an employee and shareholder of Pfizer AG. E.V.L. has received consulting fees from AbbVie, Alvotech, Amgen, Arena, Astellas, Avalo Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion Healthcare, Eli Lilly Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iota Biosciences, Iterative Health, Janssen, KSL Diagnostics, Morphic Therapeutic, Ono Pharma, Protagonist, Scipher Medicine, Sun Pharma, Surrozen, Takeda, TR1X and UCB Pharma; has received research support from AbbVie, AstraZeneca, Bristol-Myers Squibb, Celgene/Receptos, Genentech, Gilead, Gossamer Bio, Janssen, Pfizer Inc., Takeda, Theravance and UCB Pharma and is a shareholder of Exact Sciences.

Figures

Figure 1.
Figure 1.
(a) Onset and (b) duration of Headache TEAEs in the Placebo-controlled UC cohort. n1, number of events per timepoint; N1, total number of events by treatment group; TEAE, treatment-emergent adverse event; UC, ulcerative colitis.
Figure 2.
Figure 2.
(a) Onset and (b) duration of Pyrexia TEAEs in the Placebo-controlled UC cohort. a‘Ongoing’ included patients whose TEAE outcomes were unknown. n1, number of events per timepoint; N1, total number of AEs by treatment group; TEAE, treatment-emergent adverse event; UC, ulcerative colitis.
Figure 3.
Figure 3.
(a) Onset and (b) duration of Nausea TEAEs in the Placebo-controlled UC cohort. n1, number of events per timepoint; N1, total number of events by treatment group; TEAE, treatment-emergent adverse event; UC, ulcerative colitis.
Figure 4.
Figure 4.
(a) Onset and (b) duration of Dizziness TEAEs in the Placebo-controlled UC cohort. n1, number of events per timepoint; N1, total number of events by treatment group; TEAE, treatment-emergent adverse event; UC, ulcerative colitis.
Figure 5.
Figure 5.
Change in heart rate from baseline to week 2 in patients receiving etrasimod 2 mg OD with Dizziness TEAEs on days 1–3 (a) without Bradycardia and (b) following discontinuation due to Bradycardia in the Placebo-controlled UC cohort. aFor patient 1, post-dose timing of day 2 measurements was unknown. Day 2 measurements shown are the last measurements available from that day. bpm, beats per minute; TEAE, treatment-emergent adverse event; UC, ulcerative colitis.
See this image and copyright information in PMC

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