Patients with pulmonary arterial hypertension (PAH) caused by connective tissue disease benefit from treatment with Adcirca (tadalafil), but their outcomes aren’t as good as patients with idiopathic PAH, an analysis of data from two clinical trials indicates.
Safety was a particular problem with connective tissue disease patients, the evaluation showed. They experienced more serious adverse effects, including death.
The studies also showed that those who received higher doses early in their therapy benefitted more. This suggested that physicians should consider early treatment in this patient group.
The key measuring stick was patients’ ability to withstand to exercise.
The study, “Tadalafil in idiopathic or heritable pulmonary arterial hypertension (PAH) compared to PAH associated with connective tissue disease,” was published in the International Journal of Cardiology. It was led by researchers at the University of Bologna.
The two Phase 3 trials — PHIRST (NCT00125918) and PHIRST-2 (NCT00549302) — examined Adcirca in various types of PAH patients. Both trials were sponsored by Eli Lilly, the treatment’s developer. Adcirca is marketed in the U.S. by Lung Biotechnology.
In the first trial, several doses of Adcirca were compared with a placebo for 16 weeks. The second trial was a continuation that involved two doses of the drug.
Altogether, the treatments lasted 52 weeks. Patients were re-randomized to receive either 20 mg or 40 mg of Adcirca. This meant that patients who received a placebo in the first trial received the drug in the second.
All treatment groups were able to withstand exercise better, compared with the placebo takers, the analysis showed. A lower dose was less effective than the higher one. But each of the two dose levels produced similar improvement in the two patient groups.
More patients with connective tissue disease had their conditions worsen in both trials, researchers said.
Among the patients treated with 40 mg of Adcirca in both trials, 2.7 percent with idiopathic PAH and 15 percent with connective tissue PAH ended up in a worse category in the World Health Organization lung functioning scale.
The analysis also showed that the condition of those with connective tissue disease worsened sooner than idiopathic PAH patients.
In the first study, connective tissue disease PAH patients tended to have higher rates of adverse effects. In the second, adverse effects were similar. Nevertheless, severe adverse events were more common in those with connective tissue disease — 40% versus 22% in idiopathic PAH patients.
Patients with connective tissue disease tended to be older and female, the analysis showed.
Despite poorer outcomes in patients with connective tissue disease, the researchers underscored that they benefitted from early treatment.