{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:07:39Z","timestamp":1791389259329,"version":"4.3.3"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Janus kinase (JAK)-1 inhibitors have been approved for moderate-to-severe atopic dermatitis (AD). Despite favorable efficacy, their real-world infection risk profile requires further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective disproportionality analysis using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. Reports identifying upadacitinib or abrocitinib as primary suspect drugs for \u201cInfections and Infestations\u201d adverse events (AEs) in AD treatment from Q3 2019 to Q1 2025 were included. Four disproportionality methods were employed to detect infection-related safety signals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 18 infection-related positive safety signals associated with abrocitinib were identified, which include known AEs (herpes zoster, eczema herpeticum, and herpes simplex) and unexpected signals (sepsis, appendicitis, and septic shock). Upadacitinib showed 64 infection-related signals, encompassing known AEs (herpes zoster, pneumonia, and influenza) and unexpected signals (sepsis, appendicitis, and septic shock). Herpes zoster was the most frequent infection-related AE for both drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study confirms established infection risks of JAK-1 inhibitors in AD (particularly herpes zoster) and identifies novel potential safety signals (sepsis, appendicitis, and septic shock). These findings provide real-world insights into the risk of infections associated with JAK inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1694688","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T05:21:40Z","timestamp":1762147300000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Association between oral JAK-1 inhibitors and infection risks in atopic dermatitis: a retrospective analysis of the FAERS database"],"prefix":"10.3389","volume":"12","author":[{"given":"Zenan","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanglei","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/S2213-2600(25)00003-7","article-title":"Global, regional, and national burden of asthma and atopic dermatitis, 1990-2021, and projections to 2050: a systematic analysis of the global burden of disease study 2021","volume":"13","year":"2025","journal-title":"Lancet Respir Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.anai.2018.07.006","article-title":"Patient burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study","volume":"121","author":"Silverberg","year":"2018","journal-title":"Ann Allergy Asthma Immunol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"adv00161","DOI":"10.2340\/00015555-3511","article-title":"Counting the burden: atopic dermatitis and health-related quality of life","volume":"100","author":"Ali","year":"2020","journal-title":"Acta Derm Venereol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1007\/s12016-020-08799-1","article-title":"Treatments for childhood atopic dermatitis: an update on emerging therapies","volume":"61","author":"Chu","year":"2021","journal-title":"Clin Rev Allergy Immunol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1111\/all.16009","article-title":"Treatment of atopic dermatitis: recently approved drugs and advanced clinical development programs","volume":"79","author":"M\u00fcller","year":"2024","journal-title":"Allergy"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1068260","DOI":"10.3389\/fimmu.2022.1068260","article-title":"JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis: an updated review","volume":"13","author":"Huang","year":"2022","journal-title":"Front Immunol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.alit.2021.10.004","article-title":"Innovation in the treatment of atopic dermatitis: emerging topical and oral Janus kinase inhibitors","volume":"71","author":"Nakashima","year":"2022","journal-title":"Allergol Int"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/j.jaci.2021.08.009","article-title":"JAK inhibitors in the treatment of atopic dermatitis","volume":"148","author":"Chovatiya","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"ii24","DOI":"10.1093\/rheumatology\/keaa895","article-title":"The safety of JAK-1 inhibitors","volume":"60","author":"Clarke","year":"2021","journal-title":"Rheumatology (Oxford)"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1016\/j.jaci.2024.07.019","article-title":"Comparative safety of oral Janus kinase inhibitors versus dupilumab in patients with atopic dermatitis: a population-based cohort study","volume":"154","author":"Tsai","year":"2024","journal-title":"J Allergy Clin Immunol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1007\/s00228-022-03400-4","article-title":"The safety of systemic Janus kinase inhibitors in atopic dermatitis: a systematic review and network meta-analysis","volume":"78","author":"Alves","year":"2022","journal-title":"Eur J Clin Pharmacol"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.20674","article-title":"Infection risk in atopic dermatitis patients treated with biologics and JAK inhibitors: BioDay results","author":"van der Gang","year":"2025","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.jaip.2020.09.021","article-title":"Emerging causes of drug-induced anaphylaxis: a review of anaphylaxis-associated reports in the FDA adverse event reporting system (FAERS)","volume":"9","author":"Yu","year":"2021","journal-title":"J Allergy Clin Immunol Pract"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1007\/s11096-024-01713-1","article-title":"Adverse events of nivolumab plus ipilimumab versus nivolumab plus cabozantinib: a real-world pharmacovigilance study","volume":"46","author":"Oka","year":"2024","journal-title":"Int J Clin Pharm"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1016\/j.jaad.2025.05.1417","article-title":"A disproportionality analysis of thromboembolic and cardiovascular adverse event signal strength across various JAK-inhibitors based on the FAERS database","volume":"93","author":"Zheng","year":"2025","journal-title":"J Am Acad Dermatol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1016\/j.jaad.2020.11.042","article-title":"Retrospective analysis of adverse events with dupilumab reported to the United States Food and Drug Administration","volume":"84","author":"Wang","year":"2021","journal-title":"J Am Acad Dermatol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"224","DOI":"10.3238\/arztebl.m2023.0011","article-title":"Atopic dermatitis in children and adults\u2014diagnosis and treatment","volume":"120","author":"Wollenberg","year":"2023","journal-title":"Dtsch Arztebl Int"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"Itc19","DOI":"10.7326\/AITC201808070","article-title":"Herpes Zoster","volume":"169","author":"Schmader","year":"2018","journal-title":"Ann Intern Med"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e13423","DOI":"10.1111\/papr.13423","article-title":"8. Herpes zoster and post herpetic neuralgia","volume":"25","author":"Adriaansen","year":"2024","journal-title":"Pain Pract"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1111\/j.1533-2500.2010.00432.x","article-title":"Herpes zoster pain, postherpetic neuralgia, and quality of life in the elderly","volume":"11","author":"Pickering","year":"2011","journal-title":"Pain Pract"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1007\/s40257-024-00869-w","article-title":"Integrated safety update of Abrocitinib in 3802 patients with moderate-to-severe atopic dermatitis: data from more than 5200 patient-years with up to 4 years of exposure","volume":"25","author":"Simpson","year":"2024","journal-title":"Am J Clin Dermatol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"72","DOI":"10.5114\/ada.2023.135764","article-title":"Systematic review and network meta-analysis of the risk of herpes zoster with biological therapies and selective Janus kinase-1 inhibitors in atopic dermatitis","volume":"41","author":"Manzar","year":"2024","journal-title":"Postepy Dermatol Alergol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1759720x20936059","DOI":"10.1177\/1759720X20936059","article-title":"JAK inhibitors and infections risk: focus on herpes zoster","volume":"12","author":"Sunzini","year":"2020","journal-title":"Ther Adv Musculoskelet Dis"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1111\/1346-8138.16828","article-title":"Risk of herpes zoster according to past history in the general population: the Japanese Shozu herpes zoster study","volume":"50","author":"Kawahira","year":"2023","journal-title":"J Dermatol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s40121-021-00567-8","article-title":"Meta-regression of herpes zoster incidence worldwide","volume":"11","author":"Curran","year":"2022","journal-title":"Infect Dis Ther"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1007\/s40520-019-01374-5","article-title":"Vaccination for quality of life: herpes-zoster vaccines","volume":"33","author":"Lang","year":"2021","journal-title":"Aging Clin Exp Res"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.molmed.2020.06.007","article-title":"JAK-STAT targeting offers novel therapeutic opportunities in Sepsis","volume":"26","author":"Clere-Jehl","year":"2020","journal-title":"Trends Mol Med"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0140-6736(18)30696-2","article-title":"Sepsis and septic shock","volume":"392","author":"Cecconi","year":"2018","journal-title":"Lancet"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1016\/S0140-6736(15)00275-5","article-title":"Acute appendicitis: modern understanding of pathogenesis, diagnosis, and management","volume":"386","author":"Bhangu","year":"2015","journal-title":"Lancet"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1436183","DOI":"10.3389\/fphar.2025.1436183","article-title":"Disproportionality analysis of upadacitinib-related adverse events in inflammatory bowel disease using the FDA adverse event reporting system","volume":"16","author":"Wang","year":"2025","journal-title":"Front Pharmacol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"154333","DOI":"10.1016\/j.prp.2023.154333","article-title":"Manifestation of acute appendicitis as known but paradox visceral side effect of ulcerative colitis anti-inflammatory therapy with januskinase-inhibitor Tofacitinib (Xeljanz\u2122)","volume":"248","author":"Weber","year":"2023","journal-title":"Pathol Res Pract"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s41927-018-0031-x","article-title":"In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494)","volume":"2","author":"Parmentier","year":"2018","journal-title":"BMC Rheumatol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1007\/s40257-020-00548-6","article-title":"Selective JAK1 inhibitors for the treatment of atopic dermatitis: focus on Upadacitinib and Abrocitinib","volume":"21","author":"Ferreira","year":"2020","journal-title":"Am J Clin Dermatol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2247","DOI":"10.1007\/s13555-023-01000-3","article-title":"Comparative efficacy of targeted systemic therapies for moderate-to-severe atopic dermatitis without topical corticosteroids: an updated network Meta-analysis","volume":"13","author":"Silverberg","year":"2023","journal-title":"Dermatol Ther (Heidelb)"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1684\/ejd.2023.4581","article-title":"Successful treatment of atopic dermatitis by switching from upadacitinib to abrocitinib: a case report","volume":"33","author":"Tsai","year":"2023","journal-title":"Eur J Dermatol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.anai.2023.12.020","article-title":"Navigating the atopic dermatitis toolbox: challenging scenarios and shared decision-making","volume":"132","author":"Samynathan","year":"2024","journal-title":"Ann Allergy Asthma Immunol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1694688\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T05:21:41Z","timestamp":1762147301000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1694688\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":36,"alternative-id":["10.3389\/fmed.2025.1694688"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1694688","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]},"article-number":"1694688"}}