A recent study showed that patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) responded well to a combination therapy with ambrisentan and tadalafil, with a lower incidence of clinical failure when compared to therapy with either drug alone.
The response, however, was not as impressive when compared to initial use of the combination therapy in patients with idiopathic PAH/heritable PAH (iPAH/hPAH).
The results were reported in “Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial,” which was published in Annals of the Rheumatic Diseases.
The AMBITION trial (NCT01178073) was a Phase 3, randomized, double-blind, event-driven trial comparing the safety and efficacy of monotherapies against an initial combination therapy for WHO functional class II/III PAH patients. (Ambrisentan is sold under the brand names Letairis in U.S. and Volibris in EU, and tadalafil under the brand names Cialis or Adcirca.)
The study examined a group of 187 patients with CTD-PAH, 118 of whom had systemic sclerosis PAH (SSc-PAH). The group was a subset of the 500 PAH patients analyzed in the AMBITION trial. Initial combination therapy in CTD-PAH patients was compared to results in patients with iPAH/hPAH from the same trial.
The primary event being studied was the time to the first clinical failure event (death, hospitalization for worsening PAH, disease progression, or unsatisfactory long-term clinical response).
“Overall in CTD-PAH, 19% of combination therapy patients experienced a primary endpoint event and 36% of monotherapy patients experienced a primary endpoint event; in SSc-PAH, it was 21% of combination therapy and 40% of monotherapy patients,” the researchers wrote. The most common adverse event was peripheral edema.
One of the secondary endpoints was the six-minute walk distance (6MWD) test, a measure of exercise tolerance. After 24 weeks, the CTD-PAH patients who received initial combination therapy showed a greater increase in the median 6MWD than patients receiving monotherapy (42 meters more vs. 24.3 meters). In the SSc-PAH population, the results showed that patients receiving the combined therapy walked 40.9 meters more, compared to an increase of 12.2 meters in the monotherapy group.
The incidence of a greater-than-15% worsening in 6MWD during initial combination therapy was slightly higher in patients with SSc-PAH (31%) than in those with iPAH/hPAH (24%).
“This post hoc analysis of patients with CTD-PAH in AMBITION suggests that this subpopulation did at least as well on initial combination therapy compared with patients with iPAH/hPAH, both in terms of clinical failure risk reduction and improvement in exercise ability,” the researchers wrote. “In the CTD-PAH population, an aggressive approach to treatment with initial combination therapy may improve outcomes and exercise capacity as opposed to treatment with monotherapy.”