JAK inhibitors for the management of rheumatic diseases when antiphospholipid syndrome co-exists: case-based safety considerations

JAK inhibitors (JAKi) are small molecules that interact with JAK proteins, modulating the JAK-STAT signaling pathway, which plays a significant, though not yet fully understood, role in immune regulation. Due to the breadth of their mechanism of action, JAKi have shown promising results in the treatment of various immune-mediated diseases across different fields such as rheumatology or dermatology, and may represent a valuable therapeutic option for patients with multiple coexisting immune-mediated conditions. However, recent years have seen growing concerns regarding their use due to an observed increase in cardiovascular and thromboembolic events compared to anti-TNF drugs, which may complicate administration in patients with additional associated risk factors.Given the possible increase in thromboembolic events among patients treated with JAKi, various regulatory agencies advise against their use in patients with additional risk factors, such as advanced age or a prior thromboembolic event. This poses challenges in conditions like antiphospholipid syndrome (APS), an acquired hypercoagulability disorder mediated by antibodies, where thromboembolic events are a hallmark feature. To date, no publications have formally evaluated the safety of JAKi in APS patients in real-world clinical practice.Through a case-based approach, we aim to highlight the safety of these drugs for patients with APS and coexisting immune-mediated diseases, while emphasizing the importance of a careful assessment of additional risk factors and shared decision-making with the patient.