A recent study showed that patients with pulmonary arterial hypertension associated with connective tissue disease (CTD-PAH) responded well to combination therapy with tadalafil (cialis) and ambrisentan, with a lower incidence of clinical failure compared to therapy with either Of the drugs.
The response, however, was not as impressive compared to the initial use of combination therapy in patients with idiopathic PAH / heritable HAP (iPAH / hPAH).
Results were reported in “Combination of Initial Combination with Ambrisentan and Tadalafil in Connective Tissue Disease Associated with Pulmonary Arterial Hypertension (CTD-PAH): Subgroup Analysis of the AMBITION Trial,” which was published in Annals of the Rheumatic Diseases .
The AMBITION trial (NCT01178073) was a randomized, double-blind, event-controlled Phase 3 trial comparing the safety and efficacy of monotherapies with initial combination therapy for patients with WHO class II / III PAH . (Ambrisentan is sold under the brands Letairis in the United States and Volibris in the EU, and tadalafil under the brands 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 patients with CTD-PAH was compared to the results in patients with iPAH / hPAH from the same trial.
The first event that was studied was the time until the first event of clinical failure (death, hospitalization for PAH worsening, disease progression, or unsatisfactory long-term clinical response).
“Overall, in CTD-PAH, 19% of patients on combination therapy experienced a primary endpoint event, and 36% of patients in monotherapy experienced a primary endpoint event. In SSc-PAH, it was 21 % of combination therapy and 40% of patients with monotherapy, “the researchers wrote. The most common adverse event was peripheral edema.
One of the secondary endpoints was the 6-minute distance test (6MWD), a measure of exercise tolerance. After 24 weeks, patients with CTD-PAH who received initial combined treatment showed a median increase of 6MWD compared to patients receiving monotherapy (42 meters vs 24.3 meters). In the SSc-PAH population, the results showed that patients who received combination therapy walked 40.9 meters more, compared with an increase of 12.2 meters in the monotherapy group.
The incidence of a greater than 15% worsening in 6M DTC during initial combined therapy was slightly higher in patients with PAH-SSc (31%) than in patients with HAPA / iPAH (24%).
“This post hoc analysis of patients with CTD-PAH in AMBITION suggests that this subpopulation did at least as well in initial combination therapy compared to patients with iPAH / hPAH, both in terms of reducing the risk of clinical failure and The improvement in exercise capacity “wrote the researchers. “In the CTD-PAH population, an aggressive approach to treatment with initial combination therapy may improve outcomes and exercise capacity as opposed to monotherapy treatment.”