{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:37:59Z","timestamp":1782970679492,"version":"3.54.5"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Janus kinase (JAK) inhibitors are approved for several immune-mediated inflammatory disorders (IMIDs), but regulatory agencies, including the European Medicines Agency and the US Food and Drug Administration, have issued class-wide safety warnings regarding major adverse cardiovascular events, venous thromboembolism, and malignancy. Early myocardial effects after selective JAK1 inhibition have not been prospectively evaluated. We assessed cardiovascular safety and myocardial deformation after upadacitinib initiation in a real-world IMID cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective, single-centre, exploratory observational study, 36 consecutive adults with atopic dermatitis, prurigo nodularis, rheumatoid arthritis, or psoriatic arthritis initiating upadacitinib were enrolled. Transthoracic echocardiography with speckle-tracking global longitudinal strain (GLS) was performed at baseline, 1, 3, and 6 months. Echocardiographic operators were blinded to the study hypothesis. Longitudinal changes were analysed using rank-based repeated-measures models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty-six patients were included (median age 51 years; 55.6% female). Baseline left ventricular ejection fraction (LVEF) was preserved (median 56.0%, IQR 55.0\u201361.0), whereas GLS suggested subclinical myocardial dysfunction (\u221218.4%, IQR \u221219.8 to \u221216.2). No significant longitudinal changes were observed in LVEF (p=0.789), left ventricular mass index, relative wall thickness, or epicardial fat thickness, indicating no early structural or systolic harm. GLS showed a significant overall time effect (p=0.003), with a favourable trajectory at 1 month (p=0.003), sustained at 3 months (p=0.007) and 6 months (p=0.007). E\/e\u2032 increased modestly at 6 months (p=0.008) without structural remodelling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Upadacitinib initiation was not associated with early myocardial harm and showed a reassuring cardiovascular profile. A favourable GLS trajectory without LVEF change is hypothesis-generating and requires confirmation in adequately powered controlled studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1867314","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:25:20Z","timestamp":1782966320000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiovascular safety and early myocardial deformation signal after upadacitinib initiation in immune-mediated inflammatory disorders"],"prefix":"10.3389","volume":"17","author":[{"given":"Salvatore","family":"Corrao","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Internal Medicine Unit with Rheumatology, Dermatology, Diabetology and Tertiary Diabetic Foot Health-Care, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli","place":["Palermo, Italy"]},{"name":"Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE)","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Scibetta","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Internal Medicine Unit with Rheumatology, Dermatology, Diabetology and Tertiary Diabetic Foot Health-Care, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli","place":["Palermo, Italy"]},{"name":"Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR)","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Falcone","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Internal Medicine Unit with Rheumatology, Dermatology, Diabetology and Tertiary Diabetic Foot Health-Care, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignazio","family":"Cangemi","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Internal Medicine Unit with Rheumatology, Dermatology, Diabetology and Tertiary Diabetic Foot Health-Care, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Corrao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Azienda Ospedaliera Universitaria \u201cPoliclinico G. Martino\u201d, University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Calvo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Internal Medicine Unit with Rheumatology, Dermatology, Diabetology and Tertiary Diabetic Foot Health-Care, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"B1","volume-title":"EMA recommends measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders","year":"2022"},{"key":"B2","volume-title":"FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for Janus kinase inhibitors","year":"2021"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-221733","article-title":"EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome","volume":"81","author":"Drosos","year":"2022","journal-title":"Ann Rheum Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k1036","article-title":"Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications","volume":"361","author":"England","year":"2018","journal-title":"BMJ"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.31138\/mjr.300125.pac","article-title":"Analysis of cardiovascular risk factors in patients with psoriasis: a cross-sectional study","volume":"36","author":"Kahlow","year":"2025","journal-title":"Mediterr J Rheumatol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1136\/annrheumdis-2016-209775","article-title":"EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015\/2016 update","volume":"76","author":"Agca","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.12.083","article-title":"Targeting the immune system in atherosclerosis: JACC State-of-the-Art Review","volume":"73","author":"Zhao","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key276","article-title":"JAK-inhibitors: new players in the field of immune-mediated diseases, beyond rheumatoid arthritis","volume":"58","author":"Fragoulis","year":"2019","journal-title":"Rheumatol (Oxford)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s11883-020-00883-3","article-title":"Targeting inflammation to reduce residual cardiovascular risk","volume":"22","author":"Ajala","year":"2020","journal-title":"Curr Atheroscler Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa099","article-title":"Targeting cardiovascular inflammation: next steps in clinical translation","volume":"42","author":"Lawler","year":"2021","journal-title":"Eur Heart J"},{"key":"B11","doi-asserted-by":"publisher","first-page":"i4","DOI":"10.1093\/rheumatology\/key432","article-title":"Janus kinases to jakinibs: from basic insights to clinical practice","volume":"58","author":"Gadina","year":"2019","journal-title":"Rheumatol (Oxford)"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S330413","article-title":"Management of axial spondyloarthritis: insights into upadacitinib","volume":"16","author":"Braun","year":"2022","journal-title":"Drug Des Devel Ther"},{"key":"B13","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1111\/1756-185X.14447","article-title":"Are Janus kinase inhibitors safe and effective in treating the key clinical domains of psoriatic arthritis? 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