Tracleer Seen to Ease Skin Symptoms in Small Scleroderma Study

One year of treatment with Tracleer (bosentan) significantly reduces the severity of patient-reported skin symptoms in people with scleroderma, a new study suggests.

Yet, these benefits are diminished among those with more severe complications before treatment.

The study, “A patient-centered approach to the burden of symptoms in patients with scleroderma treated with Bosentan: A prospective single-center observational study,” was published in the journal Experimental and Therapeutic Medicine.

People with scleroderma commonly experience symptoms that can include digital ulcers (DUs, sores on the fingers and toes), as well as Raynaud’s phenomenon, where skin changes color and becomes numb or tingly in response to cold temperatures. These symptoms are largely caused by poorer blood flow, particularly in the extremities, as a result of damage to blood vessels.

Tracleer is approved in Europe to treat scleroderma-associated DUs. It works by blocking the activity of a signaling molecule called endothelin to widen blood vessels, increasing blood flow. The therapy, made by Actelion Pharmaceuticals, is approved in the U.S. to treat pulmonary pulmonary arterial hypertension(PAH).

Researchers in Romania evaluated the benefits of using Tracleer for a first year of treatment in 41 adults (mean age, 58.2), 28 of whom had diffuse and 13 with limited disease. All were treated at team’s rheumatology department between January 2016 and January 2017.

Two women dropped out after a month owing to elevated liver enzyme levels, which returned to normal after discontinuing treatment.

Among the remaining 39 patients, Tracleer was given at 62.5 mg twice daily for the first four weeks, then at 125 mg twice a day, with regular blood work to monitor for liver enzyme abnormalities or other treatment-related side effects.

Patient opinions of symptom severity were collected routinely by means of visual analogue scales (VAS), ranging from 0 millimeters (best/no symptoms) to 100 mm (worst/most intense symptoms). Separate scales were used to measure the severity of Raynaud’s phenomenon (VAS-R) and digital ulcers (VAS-DU).

Disease-related functional impairment was measured with the Health Assessment Questionnaire Disability Index (HAQ-DI), which measures difficulties in doing everyday tasks like dressing and washing yourself, walking or climbing stairs, and eating.

Results of all three measurements at one year of treatment showed significant improvements from baseline: 38.71 points in VAS-R, 51.41 in VAS-DU, and 0.72 points in HAQ-DI. Notably, these improvements were seen regardless of disease type (diffuse or limited). They were also independent of gender and concurrent treatments.

Higher disability scores at the study’s start (a baseline measure, indicating greater impairment) predicted a weaker response to Tracleer at 12 months, particularly in VAS-R and VAS-DU.

Twenty-three participants (56.1%) reported dyspnea, or shortness of breath. At all measured time points (every three months during the year), having dyspnea correlated with greater impairment assessed using HAQ-DI.

“Our results highlight the role of dyspnea in the persistent functional hindrance amongst the study group,” the researchers wrote. “The patient-centered approach to disability in scleroderma leads to the conclusion that SSc [scleroderma]-related dyspnea often constitutes one of the main factors involved in the decrement of life quality as well as disability.”

Age was also associated with lower HAQ-DI improvement; participants older than 60 were 64% more likely to experience less-than-average benefits. Post-treatment improvement in VAS-DU scores was associated with a better outcome in HAQ-DI.

The study’s relatively small size and the lack of a control group were limitations, the scientists said.

“Bosentan therapy may indirectly influence functionality and quality of life in patients with scleroderma by reducing the burden of Raynaud’s and DU-related symptoms. Nonetheless, patients with SSc with a decreased symptom burden at baseline exhibited improved outcomes,” they added.