Early detection, treatment initiation, and long-term health outcomes in patients with connective tissue disease-associated pulmonary arterial hypertension: A systematic literature review and expert consensus

OBJECTIVE: This study aimed to explore evidence related to long-term health outcomes for patients with connective tissue disease (CTD)-associated pulmonary arterial hypertension (PAH) and any clinical practices associated with screening, early detection, and initiation of treatments. METHODS: We conducted a systematic literature review (SLR) of observational studies and randomised controlled trials of adult patients with confirmed CTD-PAH, including systemic lupus erythematosus (SLE)-PAH, systemic sclerosis (SSc)-PAH, and mixed CTD (MCTD)-PAH. Based on the findings from our SLR, we conducted a Delphi panel to develop recommendations and consensus around early detection and initiation of appropriate treatment for patients with CTD-PAH. RESULTS: Sixty-three publications (54 studies and 9 guidelines) were included in the SLR, with 22 involving Asia-Pacific populations. Combination therapy reduced clinical worsening and mortality versus monotherapy. After three Delphi rounds, consensus was reached on the importance of early PAH screening in CTD, with disease-specific recommendations for SLE, SSc, and MCTD. Consensus was also achieved on appropriate treatments, including endothelin receptor antagonists (ERA), phosphodiesterase-5 (PDE5) inhibitors, and pulmonary vasodilators. However, long-term outcomes remain uncertain due to limited evidence. CONCLUSION: This study highlights the need for early screening and timely treatment initiation in CTD-PAH to potentially reduce adverse long-term outcomes.