Macitentan tadalafil Fixed Dose Combination (FDC) in treatment-naive and prior monotherapy patients with Pulmonary Arterial Hypertension (PAH): insights from A DUE

Abstract

Abstract Background Combination therapy is recommended for the management of pulmonary arterial hypertension (PAH). The A DUE study showed that M/T FDC, a fixed dose combination (FDC) of the endothelin receptor antagonist (ERA) macitentan 10mg (M) and the phosphodiesterase type 5 inhibitor (PDE5i) tadalafil 40mg (T), led to a clinically relevant improvement in pulmonary vascular resistance (PVR) vs macitentan and tadalafil monotherapies in PAH patients. A clinically meaningful trend for improvement in 6-minute walk distance (6MWD) in favor of M/T FDC vs macitentan and tadalafil was observed. Purpose Here we analysed the effect of M/T FDC in the subgroups of treatment-naïve and prior monotherapy patients. Methods In A DUE 187 adult PAH patients in WHO functional class II / III were randomised 2:1:1 to M/T FDC, macitentan or tadalafil if treatment-naïve, 2:1 to M/T FDC or macitentan if on prior ERA, and 2:1 to M/T FDC or tadalafil if on prior PDE5i. The treatment effect of M/T FDC vs macitentan and M/T FDC vs tadalafil was calculated using ANCOVA models for PVR (geometric mean ratios [95% CL]) and for 6MWD (mean change [95% CL]) in treatment-naïve patients and in patients on prior monotherapy (ERA or PDE5i) at randomisation. Results Treatment effects for M/T FDC versus macitentan and versus tadalafil on the change in PVR and 6MWD are reported in the table for each subgroup, along with those for the overall population. The safety profile of M/T FDC was in line with the safety profiles of macitentan and tadalafil. Conclusions In A DUE, the effect of M/T FDC vs both monotherapies on PVR and 6MWD in treatment-naïve and prior ERA/PDE5i patients was consistent with that observed in the overall population.