Nintedanib attenuates macrophage activation and mitigates both vascular and fibrotic presentations in the Fra2 transgenic mouse model of SSc.[50] The antifibrotic activity of the drug was correlated with an impairment in M2 monocyte polarization and a decrement in M2 macrophage populations.[51] Given the observed upregulation of M2 macrophages in peripheral blood of SSc patients and the central role these cells play in myocardial remodeling and HF pathogenesis, nintedanib emerges as a compelling candidate for managing inflammation-induced fibrosis in SSc-associated cardiac pathology. This evidence concerns the gene FOSL2 and systemic sclerosis.