Letairis may prevent PAH linked to scleroderma: Study

Early treatment could benefit at-risk patients, researchers say by Margarida Maia, PhD | August 20, 2024

Long-term treatment with Volibris (ambrisentan), marketed as Letairis in the U.S., may help prevent mild pulmonary vascular disease from developing into pulmonary arterial hypertension (PAH) in people with scleroderma, a study suggested.

“Early treatment and close follow-up could be beneficial in this high-risk group,” wrote the researchers from Germany and the U.K., who collaborated on the EDITA Phase 2 study (NCT02290613) and its long-term follow-up, EDITA-ON.

The study, “Effect of ambrisentan in patients with systemic sclerosis and mild pulmonary arterial hypertension: long-term follow-up data from EDITA study,” was published in Arthritis Research & Therapy.
​
Scleroderma, or systemic sclerosis, occurs when the immune system attacks the body’s own healthy tissues, and potentially affects the lungs. This can cause complications such as pulmonary vascular disease, a term for any disease that affects the blood vessels leading to or branching from the lungs.
Patients with pulmonary vascular disease are at risk of developing PAH, which causes high blood pressure in the blood vessels taking blood from the heart to the lungs, making physical activity more difficult.

Effects evident after six months
In the EDITA study, people with scleroderma who received Letairis over six months showed a significant reduction in pulmonary vascular resistance (PVR), a measure of how hard the heart has to pump blood through to the lungs, compared with those on a placebo.

The therapy blocks the receptors for endothelin, a hormone that causes blood vessels to become narrower. By blocking the effects of endothelin, Letairis allows the blood vessels to expand, lowering blood pressure and easing symptoms.

Patients who took part in the EDITA study and continued regular screening and follow-up visits were included in the EDITA-ON study to test the long-term effects of Letairis. The goal was to see if ongoing treatment could prevent the progression from mild pulmonary vascular disease to PAH.

Of the 38 patients who took part in the EDITA study, 34 were included in its long-term follow-up. Most (86.7%) were women. Of the 34 patients, 19 received the treatment, including 11 who had been first assigned to the placebo. Fifteen didn’t receive any treatment for PAH, including nine who decided not to continue on Letairis.

Over a mean follow-up period of about 2.6 years, patients receiving Letairis experienced a significant, 1.53 mmHg reduction in mean pulmonary arterial pressure, or mPAP, a measure of the pressure in the blood vessels that supply the lungs. In patients who didn’t receive treatment, mPAP increased by 1.91 mmHg.

In line with an earlier analysis that suggested Letairis as a way to help prevent PAH from developing, PAH was less common in patients receiving the therapy. One (6%) out of 17 developed PAH, compared with six (50%) out of 12 untreated patients.
​
In addition to helping prevent mild pulmonary vascular disease from developing into PAH, Letairis was well tolerated, with no severe side effects or treatment discontinuations in treated participants. However, given the number of patients in the study, “future trials in this field are needed to confirm these results,” the researchers wrote.