Immunosuppressive Therapy for Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases: Insights from Japanese Registry

Introduction: The combination of immunosuppressive therapy (IST) and pulmonary artery vasodilators has demonstrated potential effectiveness in treating pulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTD-PAH) other than systemic sclerosis (SSc). However, large-scale studies of this topic are limited. This study aimed to evaluate the effectiveness of early IST in treating PAH in patients diagnosed with non-SSc CTD-PAH. Methods: Clinical data for patients with non-SSc CTD-PAH were collected from the Japan Pulmonary Hypertension Registry spanning 2008–2021. Early IST was defined as the initiation or intensification of therapy within 3 months of PAH diagnosis. Results: The study included 141 patients (mean age 51 ± 16.7 years; 95% female), with 57 receiving early IST, across 43 centers in Japan. The primary underlying diseases were systemic lupus erythematosus, mixed connective tissue disease, and Sjögren syndrome. At baseline, there were no significant differences in hemodynamics or PAH treatment regimens between the IST and non-IST groups. However, the IST group was notably younger, had higher plasma IgG levels, and maintained better renal function. The IST group showed significantly greater improvements in mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) over 12 months (p = 0.032 and p = 0.028), along with significant reductions in all-cause (p = 0.039) and PAH-related (p = 0.020) mortalities. No significant differences in deaths due to infections or malignancies were observed between groups. Conclusion: Our data suggest that early initiation of IST may be associated with hemodynamic improvement; prospective confirmation in international cohorts is warranted.