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Introduction Systemic sclerosis (SSc) is associated with significant morbidity and mortality. Pulmonary arterial hypertension (PAH) represents a negative prognostic factor, with a 3-year survival of 50%. Selexipag, a selective prostacyclin receptor agonist, was approved in 2017 for the tratment of SSc-PAH, but few data on its use in a real-life setting are available. This study evaluated the long-term safety and effectiveness of Selexipag in a multicentric Italian cohort of SSc-PAH patients.Material and Methods Patients meeting the 2013 ACR/EULAR classification criteria for SSc, with PAH diagnosed at right heart catheterism (RHC), and treated with Selexipag, were retrospectively included. Data were analyzed with GraphPad Prism (v.9).Results Forty-four ssc-pah patients (93% female) from 12 italian referral centers were treated with selexipag for a median (interquartile range - iqr) of 19 (10-45) months ( table 1). The most common SSc skin subset was limited (79.5%), followed by sine-scleroderma (11.4%) and diffuse (9.1%). All patients had anti-nuclear antibodies (ANA), and 72.1% had anti-CENP antibodies. SSc-PAH survivors were significantly younger (p=0.02). Other clinical and laboratory characteristics were similar between groups. At the baseline 6-minutes walking distance test, SSc-PAH survivors performed significantly better than deceased patients (p=0.01). The estimated pulmonary artery pressure (PAP) (p=0.05) and tricuspid regurgitant velocity (p=0.03) at baseline echocardiography were significantly higher in deceased SSc-PAH patients. Similarly, the systolic PAP at RHC was significantly higher in deceased patients (p=0.03). The optimized median (IQR) Selexipag dose was 1600 (800-2400) microg/day and similar between groups. The median (IQR) timespan from PAH diagnosis to Selexipag start was 46 (16-175) months, with less than 30% of patients starting Selexipag within 2 years from PAH diagnosis. Reasons for Selexipag discontinuation included 5 (11.4%) adverse drug reactions (ADR), mainly diarrhea and headache, in the absence of life-threatening events, and one (2.3%) primary inefficacy. Selexipag persistency was 65.9% at 12 months and 40.9% at 24 months (figure 1). No significant differences were present in other treatments between groups. After a median (IQR) timespan of 9 (6-15) years, the survival rate was 52.3%. All patients received appropriate therapeutic adjustments, as 93.2% and 70.4% of them were on double and triple therapy for PAH at last follow-up, respectively.Conclusions Selexipag represents a valuable therapeutic option for SSc-PAH patients, with a reassuring long-term safety profile and encouraging survival data in real-life. Nonetheless, the time required to start the PAH triple combination therapy is still long. Shortening this timespan may further improve the prognosis of SSc-PAH patients.Abstract P.128 Table 1Comparison of baseline characteristics in alive and dead SSc-PAH patientsAbstract P.128 Figure 1Kaplan Meier curve of selexipag treatment persistency