Janus Kinase Inhibitor Exposure During Pregnancy in Immune-Mediated Inflammatory Diseases: A Case Series of 3 Patients
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".