Remodulin Safe, Effective in Treating CTD-PAH for 12 Months, Observational Study Shows

Subcutaneous Remodulin (treprostinil), marketed by United Therapeutics, is to be safe and effective for at least 12 months in patients with congenital heart disease-related pulmonary arterial hypertension (CTD-PAH), an observational study found.

The study, “Subcutaneous treprostinil in congenital heart disease-related pulmonary arterial hypertension,” was published in the journal Heart.

Congenital heart disease (CHD) is a well-known cause of pulmonary arterial hypertension (PAH), and patients with both conditions usually have a poor prognosis, aggravated by a lack of evidence to support effective treatment strategies.

Previous research included a clinical trial, BREATHE-5 (NCT00367770),which  showed that 16 weeks of treatment with PAH-specific therapy Tracleer (bosentan), marketed by Actelion, improves exercise capacity — assessed by the six-minute walk test (6MWT) — of CTD-PAH patients. This result led to an increased use of Tracleer in this PAH patient subgroup.

Intravenous prostacyclin, a common treatment for PAH patients, is effective, but the risk of systemic embolism (the blockage of a blood vessel) and infections is a significant drawback. Remodulin, a subcutaneous prostacyclin equivalent, has been shown to be safe and effective in treating PAH and chronic thromboembolic pulmonary hypertension patients, warranting the study of the therapy for CTD-PAH.

Researchers observed 32 adults with advanced CTD-PAH who received subcutaneous Remodulin due to either failed treatment with Tracleer (12 patients) or lack of Tracleer approval before treatment became necessary (13 patients), or who were assessed as PAH World Health Organization (WHO) functional class IV, characterized by severe symptoms present with any activity (seven patients). The patients were under the care of physicians at three centers throughout Europe.

Results showed that subcutaneous Remodulin significantly improved exercise capacity, assessed by the six-minute walk test at six months (mean increase of 58.7 meters) and 12 months of treatment (114 meters more), a greater improvement than with oral PAH medications, the researchers said.

Remodulin also improved WHO functional class and reduced the levels of B-type brain natriuretic peptide, a hormone produced in the heart used to diagnose heart failure.

Treatment with Remodulin also decreased pulmonary vascular resistance — which is an indication of the effort required for the heart’s right ventricle to pump blood past the pulmonary valve.

The most frequent adverse effects were pain and erythema (redness due to inflammation) at the infusion site. Patients were advised on how to manage pain and better handle the infusion pump system.

One patient had to discontinue treatment after eight months due to intolerable infusion-site pain, but no other major treatment-related complications were reported.

Five patients died during follow-up due to PAH after showing a decrease in exercise capacity, a sign that may identify patients with a poorer prognosis, the researchers noted.

“Whether these patients might eventually benefit from double or triple PAH-specific combination therapy needs to be assessed in future,” the team said.

“Subcutaneous treprostinil [Remodulin] is generally safe and effective for at least the first 12 months and may be considered for the treatment for CHD-related PAH,” they concluded. “Long-term clinical follow-up of this group will provide important further insights.”