S1437 Pregnancy Outcomes in the Etrasimod Clinical Program
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».