Moving From Tracleer to Letairis Seen as Safe for PAH Patients

People with stable pulmonary arterial hypertension (PAH) can safely switch from Tracleer (bosentan) to Letairis (ambrisentan) without compromising their heart function or general health status, a study from China reports.

PAH patients in Hunan province may also benefit financially by moving from Tracleer to Letairis, as it alone is covered by the medical insurance program of that province, where this study took place, its researchers reported.

The study, “Transition from Bosentan to Ambrisentan in Pulmonary Arterial Hypertension: A Single-Center Prospective Study,” was published in the International Journal of General Medicine.

High levels of endothelin 1 (ET-1), a protein that constricts blood vessels, are observed in people with PAH. Endothelin receptor antagonists (ERAs), such as Tracleer, manufactured by Janssen, and Letairis, marketed by Gilead in the U.S., block the effects of ET-1 and have been shown to ease symptoms.

Both Tracleer and Letairis are expensive in China. Monthly out-of-pocket expenses (after insurance reimbursement) are about $123 to $152 for Letairis, and $576 for Tracleer, the study noted.

“The main reason for drug transition is the financial burden of patients,” the researchers wrote. “Ambrisentan was covered by medical insurance of local government, and out-of-pocket costs of ambrisentan are only a quarter of bosentan.”

In addition, although a few studies have evaluated the effects of switching ERAs, the specific move from Tracleer to Letairis still needs to be assessed.

Researchers at Second Xiangya Hospital of Central South University in Changsha, the province’s capital city, examined whether patients with PAH could safely transition from Tracleer to Letairis by assessing their health status before and after the switch.

A total of 49 PAH patients were enrolled in the study and their average age was 34.4. Most (58.7%) had PAH associated with congenital heart disease (CHD-PAH), while 10.9% had PAH linked to connective tissue disease (CTD-PAH), and 28.3% had idiopathic PAH (iPAH), or PAH with an unknown cause.

All patients were stable with WHO functional classes II and III. Most were receiving combination therapy — most frequently Tracleer and sildenafil, sold as Revatio or as a generic in the U.S. — and all were on Tracleer for more than six months before the transition.

Patients were given Letairis at 5 mg orally once a day for the first four weeks, then adjusted to 10 mg if liver and kidney tests showed normal function. Follow-up exams occurred after the first month, and then at months three and six.

Treatment effective was primarily determined by change in exercise capacity, as measured using the 6-minute walking test (6MWT) or the distance walked in six minutes.

Other measures included changes in WHO functional classification, indicators of heart health as assessed by echocardiography and levels of the NT-proBNP biomarker, and quality of life (QoL) assessment scores.

After five months, three of these 49 people failed to finish the transition for reasons that included treatment side effects and clinical worsening.

Side effects are common to ERAs, the researchers wrote, nothing that 60.9% of the 46 patients who fully transitioned also experienced side effects on Tracleer before switching to Letairis. The most common for Tracleer were dizziness (42.9%), headaches (35.7%), and temporary reddening of the skin (35.7%).

After switching to Letairis, side effects were reported by 58.7% of these 46 patients, and  included dizziness (44.4%), headaches (37%), and heart palpitations (33.3%). Most side effects were considered mild to moderate, the researchers reported.

No statistically significant changes were observed in the WHO functional classification, exercise capacity or assessments of heart function, after the switch of ERAs.

However, the left ventricular end-diastolic dimension significantly increased from 37.65 mm to 40.26 mm after six months. (This is a measure of function of the heart chamber that pumps oxygenated blood into the aorta.)

This result is in line with a previous study reporting the transition to Letairis from Thelin (sitaxsentan) or Tracleer, the scientists said.

The QOL questionnaire was taken by the 46 participants who completed the study. The survey measured the patients’ perspectives on treatment effectiveness, side effects, ease of use, impact on daily living activities, and overall satisfaction.

Although the total QOL score did not change significantly after the switch, most patients thought Letairis more convenient as a once daily pill. Tracleer is taken twice a day.

The researchers noted a few study limitations, including its small number of participants and the fact that not all patients were adjusted to 10 mg after four weeks. In addition, patients were aware of the transition, which could have biased their views of improvement.

“This study was the first to investigate the safety, efficacy and satisfaction of PAH patients in transition from bosentan [Tracleer] to ambrisentan [Letairis] and was in patients without liver abnormalities,” the researchers wrote.

“Our results showed that the transition from bosentan to ambrisentan was safe and tolerable. It also demonstrated feasibilities for those who have the need to change their specific treatment strategies,” they concluded.