Bosentan May Lower Risk of PH in Certain Scleroderma Patients

Treatment with bosentan may lower the risk of developing pulmonary hypertension (PH) and help stabilize lung function in scleroderma patients with digital ulcers, a study suggests.

Patients who never had taken bosentan had a 3.9 times increased risk for PH compared to those on this therapy, findings show.

The study, “Effect of bosentan in pulmonary hypertension development in systemic sclerosis patients with digital ulcers,” was published in the journal PLOS One.

Digital ulcers — small sores in fingers and toes — are a frequent complication in scleroderma that result from insufficient blood flow. In pulmonary arterial hypertension (PAH), the most frequent cause of PH in scleroderma, the ulcers  occur in about 9% of patients.

Bosentan (sold as Tracleer and generics) blocks the function of endothelin-1 (ET-1), a protein that causes blood vessels in the lungs to narrow, which  increases blood pressure.

The therapy has been shown to improve exercise capacity and slow the progression of PAH, but it remains unknown whether it can prevent PH in people with digital ulcers.

Researchers at the Hospital Universitari de la Santa Creu i Sant Pau and Hospital Universitari de Vall Hebron, both in Barcelona, Spain, addressed this knowledge gap by reviewing clinical data of 222 scleroderma patients with history of digital ulcers. The majority (201 participants, 91%) were women and the group’s mean age was 63.9 years. The first manifestation of scleroderma was seen at the median age of 40. Limited cutaneous scleroderma was diagnosed in 138 patients.

In total, 59 patients (26.6%) were treated with bosentan, while the remaining 163 served as the control group.

An estimated systolic pulmonary arterial pressure above 40 mmHg, as shown in a echocardiogram exam, was considered as high risk for PH and was observed in 21% of the patients.

Participants on bosentan were being treated for at least one month, with a median treatment period of 34 months. The most-used dose — 250 mg given twice a day — was given to 60% of the patients. At least one adverse side effect was reported by 35.6% of patients, most often high levels of liver enzymes, and 27.1% had to stop the treatment. Other used vasodilators — therapies that widen blood vessels — including calcium channel blockers, phosphodiesterase type 5 (PDE-5) inhibitors, and prostanoids.

During follow-up, 13.8% of patients in the bosentan group and 23.7% in the control group developed PH.

The researchers found that people in the control group had a 3.9 times increased risk to develop PH compared to those given bosentan. A similar risk was seen in participants also not given PDE5-inhibitors, while those who had never taken prostanoids showed a 2.65 greater risk of PH.

As for lung function, patients in the bosentan group showed stabilized carbon monoxide diffusion capacity (%DLCO) — a test of the lungs’ capacity to transfer oxygen from the air sacs to the blood — while the control subjects showed lower levels of %DLCO at the end of the follow-up (65.5% vs. 60.5%).

Overall, these findings suggest that “patients who initiated bosentan to prevent DU [digital ulcers] have a lower risk to present PH estimated by echocardiography and stabilizes DLCO,” the scientists wrote.

“A randomized control trial is warranted to demonstrate a protective effect,” the team concluded.