Efficacy and safety of inhaled iloprost in Japanese patients with pulmonary arterial hypertension - Insights from the IBUKI and AIR Studies

Background: Inhaled iloprost is approved for pulmonary arterial hypertension (PAH) in many countries. IBUKI was a phase III, non-randomized, open-label study of the efficacy and safety of inhaled iloprost in Japanese patients with PAH. Methods and Results: Adults with PAH who were treatment-naive or administered endothelin receptor antagonists (ERAs) and/or phosphodiesterase type 5 inhibitors (PDE5-Is) and in NYHA/WHO functional class (FC) III/IV had inhaled iloprost (2.5 µug, increased to 5.0 µug if tolerated) 6-9 times daily for 12 weeks. Eligible patients entered a 40-week extension phase. Endpoints included change from baseline to week 12 in pulmonary vascular resistance (PVR; primary endpoint), other efficacy parameters, and safety. Data were compared with new subgroup analyses of treatment-naïve Western PAH patients from the global phase III AIR study. 27 patients received iloprost: 89% were treated with an ERA and/or PDE5-I; 70% with both. At week 12, PVR improved from baseline by -124 dyn sec cm-⁵ (95% CI, -177 to -72) and 6-min walking distance increased by 36.0 m (95% CI, 14.9 to 57.1). NYHA/WHO FC improved in 62%; none worsened. Common drug-related adverse events were headache (37%) and cough (15%); 1 patient experienced hypotension; none reported syncope or hemoptysis. There were no deaths and no unexpected long-term safety findings. AIR PAH subgroup analyses showed similar results. Conclusions: Inhaled iloprost appeared effective and safe in Japanese PAH patients, including ERA- and PDE5-I-treated patients, consistent with findings of the AIR PAH subpopulation and previous iloprost studies.