# Analysis of the Dynamics of Clinical Parameters and Serum Angiogenic Factors in Systemic Sclerosis Patients Undergoing Tocilizumab Treatment

## TL;DR

Tocilizumab treatment improves microvascular health and lung function in systemic sclerosis patients, likely through changes in key angiogenic factors.

## Contribution

Demonstrates TCZ's impact on vascular recovery and its link to pulmonary improvement via angiogenic factor modulation in SSc.

## Key findings

- Capillary density significantly increased after 6 months of TCZ treatment.
- Serum HGF levels correlated strongly with capillary density and skin score improvements.
- Decreased VEGF-A levels were associated with better pulmonary function test results.

## Abstract

Systemic sclerosis (SSc) is a systemic autoimmune disease characterised by vasculopathy and fibrosis of the skin and internal organs. In SSc, normal angiogenic processes are impaired due to abnormalities in vascular endothelial cells and pericytes. Nailfold videocapillaroscopy (NVC) is useful for evaluating microvascular injury in SSc. Tocilizumab (TCZ), an anti‐IL‐6 receptor antibody, has demonstrated efficacy in SSc‐associated interstitial lung disease (SSc‐ILD); however, its effects on vascular abnormalities in SSc remain poorly understood. We evaluated longitudinal changes in NVC findings in 13 SSc patients treated with monthly intravenous TCZ. Capillary density significantly increased at 6 months compared with baseline. This increase was positively and strongly correlated with improvements in pulmonary function test results. To further explore the correlation between NVC findings and angiogenic mediators, we quantified serum levels of seven pivotal angiogenic factors before and 6 months after TCZ initiation using a multiplex immunoassay. Among the angiogenic factors, serum levels of vascular endothelial growth factor (VEGF)‐A, platelet endothelial cell adhesion molecule (PECAM)‐1 and hepatocyte growth factor (HGF) were significantly intercorrelated and significantly decreased after 6 months of treatment. Notably, serum HGF levels showed the strongest correlation with capillary density and were also significantly correlated with modified Rodnan skin score. Furthermore, the decrease in serum VEGF‐A levels was robustly associated with improvements in pulmonary function test results. Our results collectively suggest that TCZ treatment is associated with changes in systemic vascular abnormalities and angiogenic factor profiles in SSc, which are critically involved in the pathophysiology of SSc‐associated interstitial lung disease.

This study demonstrates that tocilizumab (TCZ) treatment promotes microvascular recovery in systemic sclerosis (SSc), as evidenced by increased capillary density and that this improvement in vasculopathy is closely associated with enhanced pulmonary function. Our findings suggest that modulation of pathogenic angiogenic factor networks involving HGF, PECAM‐1 and VEGF‐A may play a key role in mediating these therapeutic effects.