THU0418 Long -term efficacy and safety of monotherapy versus combination therapy in systemic sclerosis-associated pulmonary arterial hypertension (PAH): a retrospective cohort study from the nationwide spanish scleroderma registry (RESCLE)
Authors: M. Pestaña-Fernández, M. Rubio-Rivas, N. Villalba-Jiménez, B. Marí-Alfonso, A. Guillén-Del-Castillo, M. Freire, J.A. Vargas-Hitos, J.A. Todolí-Parra, M. Rodríguez-Carballeira, G. Espinosa-Garriga, X. Corbella Virós, V. Fonollosa-Pla, C.P. Simeón-Aznar
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Monotherapy with endotelin antagonist receptors (ERA) an phosphodiesterase 5 (PDE5) inhibitors is a first choice treatment for PAH in functional class (FC) II-III, with the same grade of evidence and recommendation than combination therapy. Recently, studies have proven superiority of combination therapy against monotherapy in combined morbi-mortaliy endpoints. <h3>Objectives</h3> To demonstrate superiority of combination therapy against monotherapy in a single mortality endpoint in SSc-associated PAH. <h3>Methods</h3> Retrospective cohort study including patients from the Spanish Scleroderma Registry (RESCLE) diagnosed with SSc-associated-PAH by right heart catheterization (RHC). Patients were divided in 3 groups: monotherapy vs. sequential combination therapy (&gt;12 weeks between first and second treatment) vs. upfront combination therapy (&lt;12 weeks between treatments). Primary endpoint was mortality from any cause. <h3>Results</h3> Seventy-six patients with PAH out of 1817 participants were included. Thirty-four (45%)were receiving monotherapy [with ERA (22 patients, 29%) or PDE5 inhibitors (12 patients, 16%)], 25 patients (33%) sequential combination therapy and 17 patients (22%) upfront combination therapy. Baseline demographic, clinical and complementary tests were similar among groups. ILD (mainly moderate) was more freqüent in both combination groups in 58% vs. 80% vs. 76.4%, without statistical significance. A worse FVC/DLco in the sequential combination group was reported (2.9±1.1 vs. 1.8±0.4 vs.2.3±0.8, global p=0.085 but p=0.043 comparing monotherapy with sequential combination) and also a worse mPAP in both sequential and upfront combination groups(37.2±8.7 mmHg vs. 40.8±8.8 vs. 46±15.9, p=0.026). The treatment regimen prescribed (p=0.017) and FC at baseline (p=0.007) were found predictors of mortality. Sequential combination therapy was found a protective factor [HR=0.11 (95%CI 0.03–0.51), p=0.004] and the upfront combination therapy showed a tendency of protection [HR=0.68 (95%CI 0.23–1.97), p=0.476]. Survival rates from diagnosis of PAH among groups were: 78% vs. 95.8% vs. 94.1% at 1 year, 40.7% vs. 81.5% vs. 51.8% at 3 years and 31.6% vs. 56.5% vs. 34.5% at 5 years (p=0.007). Side effects were not significantly different among groups. <h3>Conclusions</h3> Combined sequential therapy improves survival in SSc-PAH patients, even wtih moderate ILD. Upfront combination therapy may improve survival, but did not reach statistical significants due to study limitations. Treatment regimen and FC were found as prognostic factors for survival: sequential combination therapy was a protective factor and FC was a risk factor. <h3>Disclosure of Interest</h3> None declared