why choose us

300×250 Ad Slot

Research Article: Cardiovascular safety and early myocardial deformation signal after upadacitinib initiation in immune-mediated inflammatory disorders

Date Published: 2026-07-02

Abstract:
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. 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. Thirty-six patients were included (median age 51 years; 55.6% female). Baseline left ventricular ejection fraction (LVEF) was preserved (median 56.0%, IQR 55.0–61.0), whereas GLS suggested subclinical myocardial dysfunction (?18.4%, IQR ?19.8 to ?16.2). 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? increased modestly at 6 months (p=0.008) without structural remodelling. 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.

Introduction:
The cardiovascular safety of Janus kinase (JAK) inhibitors has emerged as a pivotal concern in clinical pharmacology and rheumatology. Following the results of the ORAL Surveillance trial, which demonstrated an increased risk of major adverse cardiovascular events (MACE) and malignancy with tofacitinib relative to tumour necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis at elevated cardiovascular risk, the EMA and FDA issued class-wide safety restrictions for all approved JAK inhibitors ( 1 ,…

Read more

300×250 Ad Slot