S1437 Pregnancy Outcomes in the Etrasimod Clinical Program
Bibliographic record
Abstract
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 fetal harm. This analysis describes pregnancy outcomes in patients with maternal or paternal exposure to etrasimod during its clinical development. 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 October 31, 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 categorized as healthy newborn, medical termination, fetal death, congenital malformation, spontaneous abortion, or lost to follow-up. Results: In total, 2,091 unique patients were exposed to etrasimod in clinical trials; 593 (28.4%) were women of childbearing age (aged 16–44). There was a total of 14 pregnancies with exposure to etrasimod (9 maternal, 5 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 9 maternal exposures, pregnancy outcomes were 2 healthy newborns, 4 medical terminations (2 for unknown reasons, 1 due to an anembryonic gestation, and 1 following “signs of a missed pregnancy”), and 1 each resulting in a congenital malformation (open [patent] foramen ovale) spontaneous abortion and loss to follow-up (Table 1). Of the 5 paternal exposures, there were 2 healthy newborns, 2 spontaneous abortions, and 1 lost to follow-up (Table 1). Conclusion: Few pregnancies have been reported in the etrasimod clinical program, 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. Table 1. - Pregnancy outcomes during the etrasimod clinical development program Fetal 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) cde 1 (11.1)f Paternal exposure, n (%) (N = 5) 0 0 2 (40.0) 2 (40.0) 0 1 (20.0) 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 2 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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".