Researchers discovered that the novel drug macitentan had an acceptable safety profile when used as part of combination therapy in patients with pulmonary arterial hypertension (PAH), and published their results in Advances in Therapy.

Over the last few decades, a number of targeted therapies for PAH have become available, contributing to improved clinical outcomes. Macitentan is an oral endothelin receptor antagonist; its efficacy and safety as a drug for PAH were evaluated in SERAPHIN, the first long-term outcome clinical trial in the field of PAH. Macitentan apparently works by reducing the risk of disease progression and hospitalization for patients with PAH.

“In SERAPHIN, macitentan 10 mg was administered over a mean duration of 104 weeks and reduced the risk of morbidity and mortality events by 45% (p < 0.001) compared with placebo,” the authors of the study wrote. They analyzed data from the SERAPHIN trial, as well as from the open-label extension study that followed.


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In the SERAPHIN trial, patients (n=742) were randomly assigned to receive macitentan 3 mg once daily, macitentan 10 mg once daily, or the placebo. Endpoints included worsening PAH, the need to initiate intravenous or subcutaneous prostanoids, lung transplantation, atrial septostomy, or death. 

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In the SERAPHIN open-label study, the long-term safety and tolerability of macitentan 10 mg were assessed in patients with symptomatic PAH (n=550).

The researchers discovered that the most common adverse effects were worsening PAH, peripheral edema, and upper respiratory tract infection. This is in line with what was observed in the SERAPHIN trial. In addition, the researchers concluded that macitentan at a dose of 10 mg once daily was well-tolerated and had an acceptable safety profile. 

“As most patients were receiving background therapy at the time of macitentan initiation, these analyses help to further our understanding of the long-term benefit-risk ratio of using macitentan combination therapy and provide survival estimates for the longest follow-up period to date for PAH patients treated with PAH therapy,” the authors concluded.

Reference

Souza R, Delcroix M, Galié N, et al. Long-term safety, tolerability and survival in patients with pulmonary arterial hypertension treated with macitentan: results from the SERAPHIN open-label extensionAdv Ther. Published online July 12, 2022. doi:10.1007/s12325-022-02199-x