Background: Pulmonary arterial hypertension (PAH) remains a serious disease characterized by elevated pulmonary artery pressure (PAP) and increased pulmonary vascular resistance (PVR). Among its subtypes, PAH associated with connective tissue disease (CPAH) has the worse prognosis, because of resistance to conventional vasodilator therapy. We hypothesized that intensive immunosuppressive therapy (IIT) could improve the pulmonary hemodynamics in CPAH.
Methods and results: In our pulmonary hypertension (PH) cohort of 182 patients, we evaluated 13 consecutive patients with CPAH who received IIT combined with cyclophosphamide and glucocorticosteroids (IIT group, mean age 45 ± 8 years, 12 females and 1 male). We compared them with 8 historical controls (control group: mean age 52 ± 18 years, 8 females) for pulmonary hemodynamics and prognosis. Both groups were treated with conventional vasodilator therapy. Although the mean PAP (mPAP) remained unchanged in the control group, IIT significantly decreased mPAP (40 ± 9 to 29 ± 11 mmHg, P < 0.01) and tended to decrease PVR (700 ± 434 to 481 ± 418 dyne·s·cm⁻⁵, P=0.07). Importantly, in 6 of the 13 patients in the IIT group, mPAP was almost normalized (< 25 mmHg) and remained stabilized for more than 1 year. Furthermore, the IIT group showed significantly better prognosis compared with the control group (P<0.01).
Conclusions: These results suggest that IIT as well as conventional vasodilator therapy improves the pulmonary hemodynamics and long-term prognosis of patients with CPAH.