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Janus Kinase Inhibitors During Pregnancy and Adverse Drug Reactions: A Pharmacovigilance Disproportionality Analysis in VigiBase.

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Title: Janus Kinase Inhibitors During Pregnancy and Adverse Drug Reactions: A Pharmacovigilance Disproportionality Analysis in VigiBase.
Authors: Abolhassani N; Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland., Noseda R; Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland., Dao K; Swiss Teratogen Information Service (STIS) and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland., Girardin FR; Swiss Teratogen Information Service (STIS) and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland., Bedussi F; Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland., Ceschi A; Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland.; Clinical Trial Unit, Ente Ospedaliero Cantonale, Lugano, Switzerland.; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland., Panchaud A; Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.; Service of Pharmacy, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland., Winterfeld U; Swiss Teratogen Information Service (STIS) and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland.
Source: Clinical and translational science [Clin Transl Sci] 2025 Dec; Vol. 18 (12), pp. e70429.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: WileyBlackwell Pub Country of Publication: United States NLM ID: 101474067 Publication Model: Print Cited Medium: Internet ISSN: 1752-8062 (Electronic) Linking ISSN: 17528054 NLM ISO Abbreviation: Clin Transl Sci Subsets: MEDLINE
Imprint Name(s): Original Publication: Malden, MA : WileyBlackwell Pub., 2008-
MeSH Terms: Janus Kinase Inhibitors*/adverse effects , Pregnancy Complications*/drug therapy , Pregnancy Complications*/epidemiology , Pregnancy Complications*/chemically induced , Drug-Related Side Effects and Adverse Reactions*/epidemiology , Drug-Related Side Effects and Adverse Reactions*/etiology, Humans ; Female ; Pregnancy ; Pharmacovigilance ; Adverse Drug Reaction Reporting Systems/statistics & numerical data ; Adult ; Databases, Factual/statistics & numerical data ; Young Adult
Abstract: Janus kinase inhibitors (JAKIs) are immunomodulatory drugs used for autoimmune and inflammatory conditions. Their potential impact on pregnancy and fetal development remains a concern due to placental transfer and potential disruption of cytokine and growth factor signaling, with limited human data. This study analyzed VigiBase, the World Health Organization global pharmacovigilance database of individual case safety reports (ICSRs), to assess signals of disproportionate reporting (SDRs) for pregnancy-related adverse drug reactions (ADRs) reported with systemic JAKIs, including abrocitinib, baricitinib, deucravacitinib, fedratinib, filgotinib, itacitinib, momelotinib, pacritinib, peficitinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib. As of May 26, 2024, 163 ICSRs met inclusion criteria, mainly from North America (41.7%) and Europe (39.3%). The most frequently reported JAKIs were tofacitinib (44.8%) and upadacitinib (34.4%), primarily indicated for rheumatoid arthritis (29.4%). Among 213 pregnancy-related ADRs, spontaneous abortion was the most frequently reported event (47.9%) without representing an SDR compared with other drugs in the database (reporting odds ratio [ROR] 0.37, 95% confidence interval [CI] 0.30-0.46). Congenital anomalies were reported in 16.0% of ICSRs (43 events), but no specific organ-related patterns were identified. Prematurity occurred in 9.2% of ICSRs, without SDR compared to the full database (ROR 0.07, 95% CI 0.04-0.11). Current pharmacovigilance data from VigiBase do not indicate SDRs for spontaneous abortion or prematurity following JAKI exposure during pregnancy. Findings should be interpreted cautiously given the limitations of spontaneous reporting systems and the exploratory nature of the analysis. Further studies are needed to better characterize the JAKI safety in pregnancy.
(© 2025 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
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Contributed Indexing: Keywords: JAK inhibitors; VigiBase; disproportionality; pharmacovigilance; pregnancy
Substance Nomenclature: 0 (Janus Kinase Inhibitors)
Entry Date(s): Date Created: 20251127 Date Completed: 20251127 Latest Revision: 20251130
Update Code: 20251130
PubMed Central ID: PMC12657641
DOI: 10.1111/cts.70429
PMID: 41305879
Database: MEDLINE
Description
Abstract:Janus kinase inhibitors (JAKIs) are immunomodulatory drugs used for autoimmune and inflammatory conditions. Their potential impact on pregnancy and fetal development remains a concern due to placental transfer and potential disruption of cytokine and growth factor signaling, with limited human data. This study analyzed VigiBase, the World Health Organization global pharmacovigilance database of individual case safety reports (ICSRs), to assess signals of disproportionate reporting (SDRs) for pregnancy-related adverse drug reactions (ADRs) reported with systemic JAKIs, including abrocitinib, baricitinib, deucravacitinib, fedratinib, filgotinib, itacitinib, momelotinib, pacritinib, peficitinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib. As of May 26, 2024, 163 ICSRs met inclusion criteria, mainly from North America (41.7%) and Europe (39.3%). The most frequently reported JAKIs were tofacitinib (44.8%) and upadacitinib (34.4%), primarily indicated for rheumatoid arthritis (29.4%). Among 213 pregnancy-related ADRs, spontaneous abortion was the most frequently reported event (47.9%) without representing an SDR compared with other drugs in the database (reporting odds ratio [ROR] 0.37, 95% confidence interval [CI] 0.30-0.46). Congenital anomalies were reported in 16.0% of ICSRs (43 events), but no specific organ-related patterns were identified. Prematurity occurred in 9.2% of ICSRs, without SDR compared to the full database (ROR 0.07, 95% CI 0.04-0.11). Current pharmacovigilance data from VigiBase do not indicate SDRs for spontaneous abortion or prematurity following JAKI exposure during pregnancy. Findings should be interpreted cautiously given the limitations of spontaneous reporting systems and the exploratory nature of the analysis. Further studies are needed to better characterize the JAKI safety in pregnancy.<br /> (© 2025 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
ISSN:1752-8062
DOI:10.1111/cts.70429