Improvements and challenges of long-term survival in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension: A 10-year multi-center cohort study

Background Prior studies indicated improved survival in systemic sclerosis-associated pulmonary arterial hypertension (PAH) patients, but trends in systemic lupus erythematosus-associated PAH (SLE-PAH) survival remained unclear. Methods Analysing SLE-PAH patients from the nationwide CSTAR-PAH cohort, we divided them into two cohorts: A (2011-2016) and B (2016-2021), based on baseline right heart catheterization dates. We compared clinical characteristics, mortality, and treatment outcomes between these cohorts and with idiopathic PAH (IPAH) patients. Results We enrolled 610 and 104 patients with SLE-PAH and IPAH, respectively. Patients with SLE-PAH were younger, had a higher proportion of low-risk patients, and had a significantly higher 10-year survival rate than those with IPAH (66·6% vs. 44·1%, p < 0·001). Cohort B had a longer 6-min walk distance, lower mean pulmonary arterial pressure and pulmonary vascular resistance, a better-preserved cardiac index, and less right ventricular dilation than cohort A. More patients in cohort B received intensive immunosuppressant- and PAH-targeted therapies. The 5-year survival rate was significantly higher in cohort B (88·1% vs. 77·5%, p = 0·006). Reaching low-risk profile of PAH (hazard ratio [HR] 0·34, 95% confidence interval [CI] 0·15-0·79, p = 0·012) and reaching lupus low-disease-activity state (HR 0·33, 95% CI 0·14-0·82, p = 0·016) were independent predictors of survival. The rate of achieving low-risk profile for PAH was considerably higher in patients initially treated with intensive immunosuppressive and dual-PAH-targeted therapies. Conclusions Over the last decade in China, the clinical characteristics of patients with SLE-PAH have evolved and survival has improved. Early PAH detection and dual treatment-to-target strategies for both PAH and SLE have contributed to this improvement in survival. What is new? This is the largest multi-center prospective cohort study of SLE-PAH with the longest follow-up period describing changes in the characteristics, treatment regimen, and long-term survival of patients with SLE-PAH. Our study showed that the 5-year survival rate of patients with SLE-PAH has increased remarkably from 77·5% to 88·1% during the last decade. Our study demonstrated that reaching lupus low-disease-activity state is independently associated with reduced mortality. Significantly more patients reached low-risk profile of PAH during follow-up with initiation of intensive immunosuppressive therapy. What are the clinical implications? Our study emphasised on the importance of achieving dual treatment goals for both SLE and PAH (dual treat-to-target strategy). Earlier detection of PAH in patients with SLE, timely initiation of intensive immunosuppressive therapy, and upfront combination PAH-targeted therapy benefit patients in achieving PAH low-risk profile.