Suppressor of Tumorigenicity 2 as a Biomarker in Pulmonary Arterial Hypertension and its Association with REVEAL Risk Score in Riociguat-Treated Patients in the RESPITE Study

Purpose Suppressor of tumorigenicity 2 (ST-2) is a marker of cardiac remodeling and fibrosis that correlates with disease severity in patients with pulmonary arterial hypertension (PAH), and is thought to be a predictor of clinical worsening. We performed a post hoc analysis assessing ST-2 as a potential biomarker of likelihood of response in patients switching from phosphodiesterase type 5 inhibitors (PDE5i) to riociguat, and the association of ST-2 with REVEAL risk score (RRS) in the RESPITE study. Methods RESPITE was a 24-week, open-label, uncontrolled, Phase IIIb study in PAH patients with an insufficient response to PDE5i. Patients underwent a PDE5i washout period before receiving riociguat individually adjusted up to 2.5 mg three times daily. Responder status at Week 24 was defined as freedom from clinical worsening, improvement of ≥30 m in 6-minute walking distance, and World Health Organization functional class I/II. Data were analyzed descriptively as mean±SD. Statistical significance was assessed using t tests. Results At baseline, ST-2 was 21±15 ng/mL in the overall population (n=53), and responders (n=16) had lower ST-2 levels than non-responders (n=35) (17±8 vs 23±17 ng/mL). When patients were grouped according to RRS, ST-2 levels were lowest in low-risk patients (RRS 0-6; n=24) at baseline (15±7 ng/mL) and Week 24 (16±8 ng/mL) and highest in high-risk patients (RRS 9-13; n=17) at baseline (33±20 ng/mL) and Week 24 (25±12 ng/mL). There was a significant positive correlation between ST-2 at baseline and RRS at baseline ( r =0.71; p r =0.61; p Conclusion ST-2 levels at baseline correlated with RRS at both baseline and Week 24 in RESPITE, and were lower in responders at baseline. Therefore, there may be potential for ST-2 as a biomarker to identify patients who may be at higher risk at treatment commencement.