Combination of an endothelin receptor antagonist (ERA) and a phosphodiesterase type 5 inhibitor (PDE5i) is recommended to treat PAH. In A DUE, a fixed dose combination of macitentan 10mg and tadalafil 40mg (M/T FDC) significantly improved pulmonary vascular resistance (PVR) in patients with PAH vs macitentan (treatment effect: 29%) and tadalafil (treatment effect: 28%).

Here we examine the effect of M/T FDC according to prespecified subgroups of age, gender, region and WHO functional class (FC).

In A DUE (NCT03904693) adult, WHO FC II/III PAH patients 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 primary endpoint was change in PVR at week 16, expressed as percent of baseline. Geometric mean ratios and 95% CL were calculated using ANCOVA models for M/T FDC vs macitentan and vs tadalafil by subgroups of age, gender, region and WHO FC. Heterogeneity was assessed by interaction p-values.

Results for the primary endpoint of PVR across all subgroups are shown in the Figure.

In the A DUE study, M/T FDC consistently led to a greater improvement in PVR vs both macitentan and tadalafil monotherapies within prespecified subgroups. The treatment effect across subgroups was comparable to that in the overall population.

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