Janus Kinase Inhibitor Exposure During Pregnancy in Immune-Mediated Inflammatory Diseases: A Case Series of 3 Patients
Notice bibliographique
Résumé
Background Janus kinase inhibitors (JAKi), such as tofacitinib and upadacitinib, are targeted synthetic disease-modifying antirheumatic drugs used for treatment of systemic autoimmune inflammatory diseases. Previously, clinical trials of tofacitinib and upadacitinib excluded pregnant women, as the risks to the mother and developing fetus are unknown. Given molecular weight of approximately 350 daltons, the transplacental transfer of these medications is possible in early stages of embryogenesis. In doses far above the limits for human usage, animal models have shown that tofacitinib is feticidal and teratogenic in mice and rabbits.[1] We describe a series of 3 cases of intrauterine JAKi exposure in women with immune-mediated inflammatory diseases. Case Between Jan 2021-Oct 2024, patients who had been exposed to JAKi and assessed in the pregnancy and rheumatic diseases clinic were identified. We extracted information on maternal characteristics and pregnancy outcomes. We identified 6 patients with JAKi exposure. Three patients were on JAKi at the time of pre-pregnancy consultation but were advised to discontinue treatment in anticipation of pregnancy and switch to alternate therapy. Three patients had unexpected pregnancies while on JAKi for treatment of inflammatory arthritis. Of these, Patient 1 and Patient 2 had 16 and 13 days of post-conception exposure to upadacitinib respectively. Patient 3 had 24 days of post-conception tofacitinib exposure. All patients immediately discontinued their use of JAKi once pregnancy was confirmed. Table 1 summarizes pregnancy outcomes. Patients 1 and 2 experienced normal pregnancies, delivering via elective cesarean section at term without complications. Patient 3 required emergency c-section at 39 weeks due to breech presentation. No birth defects were observed in any of the infants. All had normal birth weights. Infant 3 required a brief admission to neonatal intensive care for observation but was discharged without any complications. Patient 1 was in drug free remission during pregnancy but restarted her JAKi at 3 months postpartum after she stopped breastfeeding. Patient 2 developed a flare in pregnancy after discontinuing therapy and was started on a TNF inhibitor with excellent response. Patient 3 was treated with hydroxychloroquine monotherapy in pregnancy and responded well. Table 1. Clinical Summary of 3 Cases of JAKi In-Utero Exposure in Women with Immune-Mediated Inflammatory Diseases Conclusion Currently, a ≥2-week washout period of JAKi is recommended prior to conception.[2] In this limited case series, inadvertent exposure of TNF inhibitors in the first 2-4 weeks of gestation did not result in any birth defects. Further studies are needed to determine the effects of JAKi on embryogenesis. [1.] Pfizer. Xeljanz: Highlights of prescribing information 2021. [2.] Russel M. Rheumatology 2022;62:e44-8.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,003 | 0,002 |
| Études des sciences et des technologies | 0,002 | 0,002 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,002 |
| Intégrité de la recherche | 0,003 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
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 source (Gemma direct ou Codex distillé), 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 ».