Opsumit Can Lower Mortality Risk in PAH Patients, Study Contends

When used alone or in combination with other therapies, Opsumit (macitentan) can lower the mortality risk in patients with pulmonary arterial hypertension (PAH), a study found.

The study, “Changes in REVEAL risk score in patients with pulmonary arterial hypertension treated with macitentan in clinical practice: results from the PRACMA study,” was published in the journal BMC Pulmonary Medicine.

Opsumit, marketed by Actelion Pharmaceuticals, is an approved oral therapy to manage PAH symptoms and slow its progression. The medication belongs to a class of vasodilator compounds called endothelin receptor antagonists (ERAs) that lower blood pressure by inducing blood vessel widening and relaxation.

The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) is a risk measure that was developed originally to predict the survival rates of newly-diagnosed PAH patients. It does so by combining information from several tests used to determine how fast PAH is progressing, including blood, heart, and lung function tests, as well as the six-minute walk test (6MWT, a measure of functional capacity).

Higher REVEAL risk scores are linked to lower chances of survival, while lower scores are associated with greater chances of survival.

Investigators in Spain reported the findings of an observational study that aimed to determine how REVEAL scores changed over time in a group of PAH patients who were receiving Opsumit for the first time.

The study, called PRACMA, included data from 81 adult PAH patients who were followed for at least six months after Opsumit treatment began at 28 clinical centers across Spain from September 2016 to September 2017.

The REVEAL risk score and risk category were calculated at the start of treatment (baseline) and after at least six months in all patients for whom information on at least seven of the 12 parameters used to calculate the REVEAL risk score was available.

Patients enrolled in the study were divided into two groups based on the timing of their diagnosis and treatment: incident group, those diagnosed in less than six months prior to the start of treatment; and prevalent group, those diagnosed in six months or more prior to treatment.

Among the 81 eligible patients of the group analyzed, 77.8% were women, and the mean age of the group was 57.2 years. More than half (50.6%) of the patients included in the analyses had either idiopathic or heritable PAH. A higher percentage of patients in the group were considered prevalent — 59.3% versus 40.7% of incident patients.

In most cases (44.4%), participants received a combination of Opsumit with another vasodilator compound belonging to the class of phosphodiesterase type 5 inhibitors (PDE-5). Opsumit monotherapy was given to 42% of the cohort.

At baseline, the mean REVEAL risk score in the overall population was 8.7 points (considered average risk), which dropped to 7.2 points (low risk) at a median follow-up time of 10.5 months.

Significant reductions in risk scores were seen in both prevalent (reduction of 1.2 points) and incident patients (reduction of 1.8 points), as well as in those receiving Opsumit alone (reduction of 1.2 points) or in combination with other therapies (reduction of 1.6 points).

At baseline, 36.8% of the patients were in the highest risk category of REVEAL. This percentage dropped to 14% after patients completed at least six months of treatment.

When the team analyzed changes in individual components of the REVEAL risk score, they found significant improvements in WHO functional class (a disease severity classification system) and 6MWT scores over the course of the study.

Significant reductions in pulmonary vascular resistance (a measure of heart strain), and in the levels of the N‐terminal pro‐brain natriuretic peptide (NT-proBNP, a prognostic marker of PAH) also were reported.

“In conclusion, in this study, treatment with macitentan improved the REVEAL risk strata and REVEAL risk score in incident and prevalent PAH patients, either in patients on monotherapy or on combination in clinical practice after at least six months of macitentan treatment,” researchers wrote.

“Further prospective studies are required to confirm these results and relate to survival prognosis in patients with PAH in clinical practice,” they added.

Of note, three authors of the study have received consulting/educational fees from Actelion, and two others were previous employees of Actelion Pharmaceuticals España.