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Background: Janus kinase (JAK) inhibitors represent a novel class of oral biologic disease-modifying anti-rheumatic drugs for the treatment of rheumatoid arthritis (RA). However, their cardiovascular safety profile is concerning regarding major adverse cardiovascular and venous thromboembolic events. Potential mechanisms implicate vascular alterations, yet the effects of JAK inhibitors on the micro- and macrocirculation remain largely understudied.
Objectives: In this prospective observational study, we investigated whether treatment with JAK inhibitors in RA is associated with significant alterations in the micro- and microvasculature within 3 months’ time.
Methods: Thirteen RA patients initiating JAK inhibitors as per treating physician decision were stuided. Eventually, 11 patients who completed the study were included in data analysis. Clinical parameters, disease activity and biochemical markers were assessed. Participants underwent 24h ambulatory blood pressure monitoring (Mobil-O-Graph device) for the assessment of 24h, day- and nighttime blood pressure (both brachial and aortic) and markers of large artery stiffening [pulse wave velocity (PWV), augmentation index]. Carotid intima media-thickness was measured with ultrasound. Nailfold videocapillaroscopy was applied to assess a number of capillaroscopic parameters. All procedures were performed at baseline and repeated 3 months after treatment.
Results: Treatment with JAK inhibitors was not associated with any differences in brachial and aortic blood pressure, as assessed throughout the whole 24h, daytime and nighttime period. Markers of macrovascular function and morphology (arterial stiffness, carotid atherosclerosis) remained unaltered, with the only exception of nighttime PWV which was significantly elevated at follow-up (Table 1). However, treatment with JAK inhibitors significantly decreased venous capillary limb, apical width and capillary length, and increased the number of ramified capillaries and the total number of abnormalities (Table 2).
Conclusion: Treatment with JAK inhibitors may exert significant effects on microcirculation as assessed with nailfold videocapillaroscopy within three months‘ time, whereas macrovascular structure and function appear largely unaffected. Whether alterations in the microvasculature induced by JAK inhibitors may mediate increased cardiovascular risk warrants further investigation.
REFERENCES: NIL.
Changes in arterial stiffness and carotid atherosclerosis from baseline to three-month treatment with JAK inhibitors.
| JAK inhibitors-treated patients | |||
|---|---|---|---|
| Baseline | Follow-up | P value | |
| Arterial stiffness | |||
| 24h PWV (m/s) | 7.4±0.7 | 7.7±1.0 | 0.086 |
| Daytime PWV (m/s) | 7.5±0.7 | 7.8±1.0 | 0.105 |
| Nighttime PWV (m/s) | 7.2±0.7 | 7.6±1.0 | 0.017 |
| 24h AIx (%) | 24.5±6.6 | 26.9±6.7 | 0.223 |
| Daytime AIx (%) | 25.1±6.3 | 26.6±6.1 | 0.451 |
| Nighttime AIx (%) | 22.5±8.8 | 28.3±10.2 | 0.059 |
| Carotid atherosclerosis | |||
| IMT, right carotid artery (mm) | 0.60±0.11 | 0.61±0.11 | 0.801 |
| IMT, left carotid artery (mm) | 0.64±0.19 | 0.69±0.17 | 0.301 |
| Mean carotid IMT (mm) | 0.62±0.15 | 0.65±0.14 | 0.471 |
JAK: janus kinase; PWV: pulse wave velocity; AIX: augmentation index; IMT: intima-media thickness
Continuous variables are presented as mean±SD.
Changes in capillaroscopic parameters from baseline to three-month treatment with JAK inhibitors.
| Baseline | Follow-up | P value | |
|---|---|---|---|
| Capillary density (n/mm 2 ) | 9.0 (2.0) | 9.5 (1.0) | 0.763 |
| Avascular areas, n (%) | 3 (27.3) | 6 (54.5) | 0.375 |
| Capillary width (μm) | 31.0 (9.5) | 33.3 (5.4) | 0.214 |
| Arterial limb (μm) | 10.6±2.1 | 10.7±1.3 | 0.970 |
| Venous limb (μm) | 12.5±2.1 | 11.4±1.6 | 0.047 |
| Apical width (μm) | 28.5±4.7 | 25.5±2.9 | 0.044 |
| Capillary length (μm) | 164.8±53.8 | 133.4±41.5 | 0.028 |
| Internal diameter | 13.2±2.2 | 13.3±2.0 | 0.849 |
| Microhemorrhages, n (%) | 2 (18.2) | 0 (0) | 0.500 |
| Ramified capillaries (loops/mm 2 ) | 0.5 (1.0) | 1 (1) | 0.020 |
| Bushy capillaries (loops/mm 2 ) | 0 (0) | 0 (0) | 0.564 |
| Tortuous capillaries (loops/mm 2 ) | 1 (1) | 2 (1) | 0.214 |
| Crossed capillaries (n/mm 2 ) | 2 (1) | 2 (2) | 0.157 |
| Subpapillary venous plexus, n (%) | 5 (45.5) | 5 (45.5) | 1.000 |
| Total number of abnormalities, n | 3.6±1.6 | 5.2±1.2 | 0.036 |
JAK: janus kinase
Continuous variables are presented as mean±SD or median (interquartile range).
Acknowledgements: NIL.
Disclosure of Interests: None declared.