The aim of our study was to investigate the association of four pharmacogenetic variants, namely TPMT rs1800460, TPMT rs1142345, MTHFR rs1801133 and SLCO1B1 rs4149056 correlated with AZA and MTX respectively, with the risk of severe disease outcome in patients with SSc, defined as pulmonary fibrosis (PF), kidney insufficiency, right ventricle systolic pressure (RVSP), hypocomplementemic urticarial vasculitis (HUV) and ratio between forced vital capacity (FVC) and diffusing capacity of carbon monoxide (DLCO). Here, TPMT is linked to systemic sclerosis.