Volibris (ambrisentan) given to treat adults in China with pulmonary arterial hypertension (PAH) caused by connective tissue disease led to significant improvements in exercise capacity without signs of clinical worsening over 24 weeks, a study reported.
Improvements were also seen in biomarker levels of heart function, scores measuring breathing ability, and WHO functional classifications.
The study, “Efficacy and safety of ambrisentan in Chinese patients with connective tissue disease-pulmonary arterial hypertension: a post-hoc analysis,” was published in the journal BMC Cardiovascular Disorders.
The treatment’s efficacy, both alone and in combination with other medicines, has been evaluated in previous studies in patients with PAH caused by CTD (CTD-PAH). These studies demonstrated improvements in exercise capacity, but mostly included people of European descent. Information on patients of Asian ethnicity is limited.
An open-label, Phase 3 study (NCT01808313) conducted in Chinese patients with PAH confirmed Volibris’ ability to improved exercise capacity over a 24-week treatment period.
As about 53% of all people enrolled had CTD-PAH, researchers at the Peking Union Medical College & Chinese Academy of Medical Sciences, along with investigators at various local hospitals and GSK (China), used data from this Phase 3 study to evaluate the efficacy of Volibris in this patient subgroup.
Data were available for 64 adult CTD-PAH patients (out of 67 who finished study) — 41 had PAH associated with systemic lupus erythematosus and 23 did not. Their median age was 40 and most were women.
Patients received a 5 mg oral dose of Volibris once daily for 12 weeks, followed by a 12-week dose adjustment period in which doses were increased up to 10 mg depending on the patient’s tolerance. The average time of exposure to the therapy was about 164 days; additional medications to treat CTD included hydroxychloroquine, glucocorticoids, and immunosuppressants.
The primary endpoint was a change in exercise capacity over 12 weeks, as measured by the 6-minute walking test (6MWT) or the distance walked in six minutes.
Other endpoints included changes in 6MWT over 24 weeks, in the heart function biomarker NT-proBNP, as well as in WHO functional classifications (WHO FC) and Borg Dyspnoea Index (BDI; a measure of breathing ability) scores over 12 and 24 weeks.
Use of Volibris led to a significant improvement in the 6MWT of 63.8 meters from baseline or the study’s start (mean 366.4 meters) at 12 weeks, and of 73.2 meters at 24 weeks. The improvement in CTD-PAH patients was greater than that seen in IPAH or HPAH patients, but the difference was not statistically significant.
The NT-proBNP levels in CTD-PAH patients decreased significantly with treatment at both 12 weeks (minus 1156.8 nanograms/L) and 24 weeks (minus 1095.5 nanograms/L) compared to baseline. While a significant decrease was also seen in patients with either IPAH or HPAH, the reduction was more pronounced in the CTD-PAH subgroup.
Decreases in BDI scores from baseline (average of 2.7) were observed at 12 weeks (minus 0.6) and 24 weeks (minus 0.4). The difference was not statistically significant when compared with the IPAH/HPAH subgroup.
The WHO functional classification improved by one class — from class III to class II — in 29 of the CTD-PAH patients by week 12. By week 24, 31 patients had moved from class III to class II, and three others improved from class II to class I. More CTD-PAH patients showed WHO functional classification improvements compared with IPAH/HPAH patients.
Heart rates, measured at one and two minutes after exercise, were also significantly slower (a reduced change in heart rate recovery from baseline to week 24) with treatment.
At least one adverse event was reported by 52 (73.2%) CTD-PAH patients, with most being mild (41%) or moderate (27%). The most common side effect was flushing. These safety finding were “similar to that in the earlier studies” conducted in European and Chinese PAH populations.
Overall, Volibris “ showed significant improvement in exercise capacity and no clinical worsening in the majority of Chinese patients with CTD-PAH in the 24-week treatment period,” the researchers wrote.
According to the team, “results of the current analysis provide substantial evidence regarding the efficacy of ambrisentan in CTD-PAH population and warrant further research in this direction.”
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