Background: Janus kinase (JAK) inhibitors constitute a novel class of oral biologic disease-modifying antirheumatic drugs for patients with rheumatoid arthritis (RA). However, their use has been associated with increased risk of major cardiovascular events. We investigated whether treatment with JAK inhibitors exerts significant alterations in the micro- and microvasculature in RA patients. Methods: Thirteen patients with RA initiating treatment with JAK inhibitors were prospectively studied. Eventually, data from 11 patients who completed the study were analyzed. Procedures were performed at baseline and 3 months after treatment. Nailfold videocapillaroscopy was applied to detect alterations of the dermal capillary network. Participants underwent 24 h ambulatory blood pressure monitoring (Mobil-O-Graph device) for the assessment of blood pressure (both brachial and aortic) and markers of large artery stiffening [pulse wave velocity (PWV), augmentation index] throughout the whole 24 h and the respective day- and nighttime periods. Carotid intima–media thickness was assessed with ultrasound. Results: Three-month treatment with JAK inhibitors was not associated with any differences in brachial and aortic blood pressure, arterial stiffness, and carotid atherosclerosis, with the only exception of nighttime PWV, which was significantly elevated at follow-up. However, three-month treatment with JAK inhibitors induced significant microvascular alterations and increased the total number of capillaroscopic abnormalities. Conclusions: Three-month treatment with JAK inhibitors may exert significant effects on microcirculation as assessed with nailfold videocapillaroscopy, whereas macrovascular structure and function appears largely unaffected. Further research toward this direction may add substantial information to the available literature regarding cardiovascular aspects of JAK inhibitors in RA.

Precapillary pulmonary hypertension (PH) is a significant complication of systemic sclerosis (SSc). It represents one of the leading causes of morbidity and mortality, correlating with a significantly dismal prognosis and quality of life. Despite advancements in the management of patients with pulmonary arterial hypertension associated with SSc (SSc-PAH), no significant improvement has been reported in survival of patients with precapillary SSc-PH associated with extensive lung parenchyma disease. International expert consensus and guidelines for the management of PH recommend annual screening of SSc patients for early detection of pre-capillary PH. The implementation of screening algorithms capable of identifying patients with a high likelihood of developing PH could help limit unnecessary right-heart catheterization procedures and prevent significant delay in diagnosis. Furthermore, early initiation of up-front combination targeted therapy in patients with PAH has shown increase in survival rates, indicating that timely and aggressive medical therapy is key for stabilizing and even improving functional class, hemodynamic parameters and 6 min walking distance (6MWD) in this population. Further research is warranted into the benefit of PAH-targeted therapies in patients with PH associated with lung disease. Lastly, we discuss the potential role of immunosuppression using biologic agents in the therapeutic management of precapillary PH in SSc patients.