Introduction
Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC) and in development for the treatment of other immune-mediated inflammatory diseases. Based on animal studies at clinically relevant doses, etrasimod may cross the placenta and cause foetal harm. This analysis describes pregnancy outcomes in patients with maternal or paternal exposure to etrasimod during its clinical development.
Aims & Methods
Reports of pregnancy or partner pregnancy during etrasimod exposure were identified from all phase 1–3 completed or ongoing open-label studies up to 31 October 2023. These studies included healthy volunteers or patients with UC, Crohn’s disease, atopic dermatitis, eosinophilic esophagitis or alopecia areata. In all studies, pregnancy was an exclusion criterion, women of childbearing age were required to use contraception and study drug was discontinued in any female patient that became pregnant. Pregnancy outcomes were categorised as healthy newborn, medical termination, foetal death, congenital malformation, spontaneous abortion or lost to follow-up.
Results
In total, 2091 unique patients were exposed to etrasimod in clinical trials; 593 (28.4%) were females of childbearing age (aged 16–44). There was a total of 14 pregnancies with exposure to etrasimod (nine maternal, five paternal). All pregnancy exposures were limited to the first trimester. Median (range) age of women with maternal etrasimod exposure was 28.0 (18–36) years. Estimated length of maternal etrasimod exposure (from last menstrual period until last etrasimod dose) ranged from 22 to 79 days. Of the nine maternal exposures, pregnancy outcomes were two healthy newborns, four medical terminations (two for unknown reasons, one due to an anembryonic gestation and one following “signs of a missed pregnancy”) and one each resulting in a congenital malformation (open [patent] foramen ovale), spontaneous abortion and loss to follow-up (Table). Of the five paternal exposures, there were two healthy newborns, two spontaneous abortions and one lost to follow-up (Table).
Table. Pregnancy outcomes during the etrasimod clinical development programme
|
|---|
Data on pregnancy events and outcomes were taken from the Pfizer internal data warehouse on serious adverse events that included pregnancy.
aPremature 34-week delivery due to premature rupture of membranes, open (patent) foramen ovale (heart) with circulatory failure and transient tachypnoea of the newborn, which were all considered non-serious concomitant events.
bBoth patients had full-term birth, caesarean delivery.
cReasons for medical termination were not known in two cases.
dOne patient with an anembryonic gestation where umifenovir (received for a respiratory tract infection) was a co-suspected drug. Umifenovir is contraindicated for use in pregnancy.
eOne patient was reported as having “signs of a missed pregnancy at 5 weeks and 6 days” the day prior to elective medical pregnancy termination.
fPatient was diagnosed as having an ectopic pregnancy prior to being lost to follow-up.
N, total number of patients; n, number of patients with a given outcome. |
| Foetal death | Congenital malformation
| Spontaneous abortion
| Healthy newborn
| Medical termination
| Lost to follow-up
|
Maternal
exposure, n (%)
(N = 9)
| 0 | 1 (11.1)a
| 1 (11.1)
| 2 (22.2)b
| 4 (44.4)c,d,e
| 1 (11.1)f
|
Paternal
exposure, n (%)
(N = 5)
| 0 | 0 | 2 (40.0)
| 2 (40.0)
| 0 | 1 (20.0) |
Conclusion
Few pregnancies have been reported in the etrasimod clinical programme, with no clear trends on the risk of maternal or paternal etrasimod exposure. Ongoing etrasimod studies and larger post-marketing registries will further inform on the safety of etrasimod during pregnancy. Women of child-bearing potential should use birth control while on etrasimod.
Disclosure
KBG has received research support from Celltrion, Galapagos, and Pfizer Inc; speakers’ honoraria and/or consulting fees from AbbVie, Celltrion, Ferring Pharmaceuticals, Immunic Therapeutics, Janssen, Novartis, Pfizer Inc, Samsung Bioepis, Takeda, and Tillotts. MC is a consultant/advisor for Gilead, Janssen, Lilly, Pfizer Inc, Takeda and Tillots; has received grant/research support from Galápagos, Janssen and Pfizer Inc; is an investigator for AbbVie, Boehringer Ingelheim Ltd., Celgene, F Hoffman La Roche, Genentech, Hospira, Janssen Cilag International LV, Janssen Cilag International NV, Millenium Pharmaceuticals, Shield, Shire and Takeda and principal investigator for AbbVie, Ferring Pharmaceuticals, Janssen, MSD and Takeda. MTA is a consultant for Janssen, Prometheus Bioscience, Takeda, Gilead, Eli Lilly, AbbVie Inc, Amgen, Arena Pharmaceuticals, Bristol Myers, Celsius, Microba Life Sciences, Pfizer, UCB Biopharma, Prometheus and Janssen Biotech Inc. YL is an advisory committee/board member for Takeda, Pfizer, Eli Lilly, Janssen, AbbVie, Celltrion, Sandoz and consultant for Takeda, Pfizer, Eli Lilly, Janssen and AbbVie. ES is a consultant for AbbVie and Janssen and has received speaker fees from Biogen, Dr. Falk Pharma, Janssen, AbbVie, Takeda, BMS, Celltrion and CED Service GmbH. AM is an employee of Pfizer Ltd and shareholder of Pfizer Inc. KL is an employee of Pfizer AG and shareholder of Pfizer Inc. JW, CCS and MD are employees and shareholders of Pfizer Inc. KW is an employee and shareholder of Pfizer Canada Inc. UM is an advisory/committee board member for Merck (DSMB) and Rana Therapeutics; consultant for Abbvie, Bristol Myers Squibb, Boeringher Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Pfizer, Protagonist, Roivant and Takeda and has received grant/research support from Leona and Harry Helmsley Trust.
