Evaluation of patients with severe pulmonary hypertension and a range of comorbidities prescribed inhaled treprostinil

Patients with pulmonary arterial hypertension (PAH) and additional cardiac or pulmonary comorbidities have a poor prognosis and are frequently excluded from clinical trials. The purpose of this study was to evaluate outcomes of patients with pulmonary hypertension (PH) secondary to a range of World Symposium on PH (WSPH) groups treated with inhaled treprostinil (iTRE) in a real-world setting. Patients with PH who were started on treatment with iTRE at Duke University were classified by WSPH Group and included patients with Groups 1, 2, 3, combined Groups 2 and 3 (PH in the setting of left heart failure and chronic lung disease), Group 4, and Group 5 PH. Time to disease worsening, a composite of death, lung transplantation, or transition to intravenous prostacyclin was compared by WSPH Group, and iTRE treatment status using a multivariable Cox proportional hazards model adjusted for age, sex, and Registry to Evaluate Early and Long-Term PAH Disease Management Lite 2 risk score. Treatment with iTRE was defined as a time-varying covariate. The cohort included 270 patients with PH: 30.6% Group 1; 10% Group 2; 32.2% Group 3; 11.1% combined Groups 2 and 3; and 15.9% with either Group 4 or 5 PH. At 3 and 6 months of follow-up, 24.8% and 38.9% of patients, respectively, were no longer treated with iTRE. Patients who discontinued treatment with iTRE had a significantly higher risk of disease worsening (adjusted hazard ratio: 5.02, 95% confidence interval: 3.44-7.31). There was no significant difference in disease worsening among WSPH Groups. In a real-world setting, many patients with PH secondary to a range of WSPH Groups tolerated treatment with iTRE. Future studies should phenotype patients with PH based on both comorbidities and therapeutic responsiveness.