Conceptual framework for the definition of disease modification in systemic sclerosis and potential implications for drug development and clinical study design

Definition of disease modification in SSc requires a nuanced approach considering molecular, mechanistic and clinical aspects.

Disease-modifying treatments in SSc should target core pathways or cells rather than regulatory mechanisms.

Disease-modifying treatments should show sustained effects on disease activity and prevent progression of damage across organs, manifestations, disease stages and disease endotypes.

The complex, variable nature of SSc needs to be reflected in preclinical drug development and clinical trial designs to demonstrate disease-modifying effects of drug candidates.