Evaluation of non-invasive low-risk criteria in patients with connective tissue disease-associated pulmonary arterial hypertension: A 12-months analysis from the INSPECTIO study

BACKGROUND: Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) is a progressive, high-risk subtype of PAH characterized by immune-mediated vascular remodeling, poor treatment response, and reduced survival. Real-world data on therapeutic response and risk evolution in this population remain limited. METHODS: This post hoc analysis of the multicenter, prospective INSPECTIO study evaluated the CTD-PAH subpopulation treated with macitentan and/or selexipag. The primary endpoint was the change in the number of non-invasive low-risk criteria (World Health Organization functional class I-II, 6-min walk distance >440 m, BNP <50 ng/L or NT-proBNP <300 ng/L) from baseline to 12 months. Secondary endpoints included changes in risk stratification, 6MWD, BNP/NT-proBNP levels, echocardiographic and hemodynamic parameters, a comparison with the non-CTD PAH population of the study was also conducted. RESULTS: Among a total of 176 patients enrolled in the INSPECTIO study, 64 (36.4 %) had CTD-PAH. The CTD group, with a larger prevalence of systemic sclerosis (SSc) patients, was predominantly female (93.8 %) and older than the non-CTD group (66.4 vs. 59.6 years, p = 0.0005). The mean number of non-invasive low-risk criteria increased significantly from baseline to Month 12 (+0.20; p = 0.0389), with 10.9 % of CTD patients achieving three low-risk criteria at Month 12. Secondary endpoints (Investigator's risk assessment, 6MWD, BNP, NT-proBNP, echocardiographic and hemodynamic parameters, baseline therapeutic strategy, vital signs) remained collectively stable. CONCLUSIONS: CTD-PAH patients showed improvement in non-invasive risk criteria and stabilization of functional, echocardiographic, and hemodynamic parameters under macitentan and/or selexipag therapy. Despite the observational nature and small sample size, this real-world analysis supports the use of risk-based treatment strategies and close monitoring in this patient population.