Long-term Efficacy and Safety of Monotherapy Versus Combination Therapy in Systemic Sclerosis-associated Pulmonary Arterial Hypertension: A Retrospective Cohort Study from the Nationwide Spanish Scleroderma Registry (RESCLE)

Objective Monotherapy is an option as first line therapy for pulmonary arterial hypertension (PAH). However, combination therapy is a beneficial alternative. Our objective was to evaluate efficacy of monotherapy vs. combination therapy in Systemic Sclerosis (SSc)-associated PAH patients. Methods All patients with SSc-associated PAH from the Spanish Scleroderma Registry (RESCLE) were reviewed. Patients were split up in three groups: monotherapy vs. sequential combination vs. upfront combination. Primary endpoint was death from any cause at 1, 3 and 5 years from PAH diagnosis. Results 76 patients (4.2%) out of 1817 had SSc-related PAH. 34 patients (45%) were receiving monotherapy [ERA (22, 29%) or PDE5 inhibitors (12, 16%)], 25 (33%) sequential combination, and 17 (22%) upfront combination. A lower FVC/DLco in the sequential combination group was reported (2.9±1.1 vs. 1.8±0.4 vs. 2.3±0.8, p=0.085) and also a higher mPAP in combination groups (37.2±8.7 mmHg vs. 40.8±8.8 vs. 46±15.9, p=0.026) at baseline. Treatment regimen (p=0.017) and functional class (p=0.007) were found independent predictors of mortality. Sequential combination was found an independent protective factor [HR=0.11 (95%CI 0.03-0.51), p=0.004], while upfront combination showed a trend [HR=0.68 (95%CI 0.23-1.97), p=0.476]. Survival from PAH diagnosis among monotherapy, sequential and upfront combination groups was: 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. Conclusion Combination sequential therapy improved survival in our cohort.