P0853 - Low Incidence of Macular Edema in Patients in the Etrasimod Clinical Program

Marla C. Dubinsky, MD¹, Joseph Wu, PhD², Aoibhinn McDonnell, PhD³, Krisztina Lazin, MD⁴, Martina Goetsch, MD⁴, Diogo Branquinho, MD, MSc⁵, Irene Modesto, MD⁵, Alessandro Armuzzi, MD, PhD^6
1Icahn School of Medicine at Mount Sinai, New York, NY; ²Pfizer Inc., Cambridge, MA; ³Pfizer Ltd., Sandwich, England, United Kingdom; ⁴Pfizer AG, Zürich, Zurich, Switzerland; ⁵Pfizer Inc., New York, NY; ⁶IBD Unit, IRCCS Humanitas Research Hospital, Rozzano, Humanitas University, Pieve Emanuele, Milan, Lombardia, Italy

Introduction: Sphingosine 1-phosphate (S1P) receptor modulators have been associated with an increased risk of macular edema.¹ Etrasimod is an oral, once-daily (QD), selective S1P_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC) and is in development for the treatment of other immune-mediated inflammatory diseases.

Methods: We assessed the proportions and incidence rates (IRs; patients with events per 100 patient-years [PY] of exposure) of Macular edema and Cystoid macular edema in a comprehensive analysis of safety data from the etrasimod clinical program. UC data were analyzed in two cohorts: Placebo-controlled UC (completed phase [ph] 2 OASIS, ph 3 ELEVATE UC 52 and ELEVATE UC 12) and All UC (patients treated with etrasimod in the Placebo-controlled UC plus open-label extension [OLE] studies; completed ph 2 OASIS OLE and ongoing ph 3 ELEVATE UC and ES101002 OLE studies, both datacut at January 31, 2022). Data from completed ph 2 studies in Crohn’s disease (CULTIVATE substudy A) and placebo-controlled studies in eosinophilic esophagitis (VOYAGE), alopecia areata, and atopic dermatitis (ADVISE) were also analyzed.

Results: Across the etrasimod UC clinical program, 942 patients received ≥ 1 dose of etrasimod 2 mg QD, with 757.9 PY of exposure. In the Placebo-controlled UC cohort, Macular edema was reported in two patients (0.3%; IR 0.70) receiving etrasimod 2 mg QD (one patient with long-term corticosteroid use in ELEVATE UC 52 and one patient with prior uveitis in ELEVATE UC 12, which was not considered clinically significant by the investigator) and one patient (0.3%; IR 0.84) receiving placebo (ELEVATE UC 12). In the All UC cohort, one patient (0.1%; IR 0.13) receiving etrasimod 2 mg QD during the ELEVATE UC OLE reported two events of Cystoid macular edema (Table). Four of five Macular edema events began at Days 74–94, all were non-serious and only one event led to treatment discontinuation. No events of Macular edema were reported in studies of etrasimod in other indications (Table).

Discussion: The incidence of Macular edema in patients treated with etrasimod in the clinical program was low and generally comparable with placebo. These results are consistent with other S1P receptor modulators¹ and provide clinically relevant information on events of Macular edema.

Reference:
Bencardino S et al. J Clin Med 2023; 12: 5014.


Disclosures:


Marla C. Dubinsky, MD¹, Joseph Wu, PhD², Aoibhinn McDonnell, PhD³, Krisztina Lazin, MD⁴, Martina Goetsch, MD⁴, Diogo Branquinho, MD, MSc⁵, Irene Modesto, MD⁵, Alessandro Armuzzi, MD, PhD⁶. P0853 - Low Incidence of Macular Edema in Patients in the Etrasimod Clinical Program, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.