Multi-category Index Can Predict Adempas-treated PAH Patients’ Outcomes, Study Finds

Using a multi-category index to assess pulmonary hypertension patients’ response to Adempas (riociguat) can help doctors predict their survival, a study reports.

REVEAL risk scores can also help doctors predict patients’ progression-free survival — or the length of time it takes for their disease to worsen, researchers said.

The study, which appeared in The Journal of Heart and Lung Transplantation, is titled “REVEAL risk scores applied to riociguat-treated patients in PATENT-2: Impact of changes in risk score on survival.”

Scientists used information in a large registry of pulmonary arterial hypertension patients to develop the index a number of years ago. It is a composite of their scores in nine categories, including lung function test results, echocardiogram readings, exercise test results, and whether or not they have other diseases.

The REVEAL part of the index’s name comes from the acronym for the database, whose full title is the Registry to Evaluate Early and Long-term PAH Disease Management. Doctors can use the registry, which was established in 2006, to help manage a PAH patient’s disease. It’s also an important resource for researchers.

Doctors developed a REVEAL risk score calculator — or RRS calculator, for short — to get an idea at different stages of the disease of the risk of a patient having a poor outcome. They can also use it to evaluate patients’ response to treatment.

A research team decided to study RRS scores’ ability to predict the long-term outcomes of patients treated with Bayer’s Adempas, compared with a placebo. The focus of their analysis was changes in their RRS scores during treatment.

The team’s first step was to review other measures of patients’ response to Adempas in two clinical trials. The next step was to calculate their RSS scores.

The trials were the Phase 3 PATENT-1 study (NCT00810693) and its extension, PATENT-2 (NCT00863681). They investigated Adempas’ effectiveness and safety during the 12 weeks of the PATENT-1 trial in 396 patients, and the same measures in the first 12 weeks of the PATENT-2 trial.

An indication of Adempas’ effectiveness in the PATENT-1 study was that it significantly improved patients’ exercise capacity, compared with a placebo. The measure researchers used was how far patients could walk in six minutes.

Another measure demonstrating Adempas’ effectiveness was improvements in patients’ World Health Organization functional class scores. Still another was better scores on the Borg dyspnea index, which assesses patients’ shortness of breath. And a fourth was increases in the time it took for patients’ disease to worsen.

Adempas also improved patients’ six-minute walk distance scores and WHO functional class scores in the first 12 weeks of the PATENT-2 extension study.

Researchers used the trial data to calculate patients’ RRS scores before and after their treatment. They then grouped patients into five risk categories.

Those at the lowest risk of a poor outcome had RRS scores of 1 to 7. An average risk score was 8, a moderately high risk score 9, a high risk 10 or 11, and a very high risk score 12 or higher.

Adempas significantly improved patients’ RRS scores, compared with a placebo, in the initial trial. And the improvement continued in the first 12 weeks of the extension.

An important conclusion was that ”RRS at baseline [before treatment started] and at PATENT-1 Week 12 were both significant predictors of survival,” the researchers wrote.

Adempas-treated patients’ lower risk of a poor outcome held up in the extension study, they wrote. Patients who received a placebo in the PATENT-1 study also saw their risk scores drop after being switched to Adempas in the extension.

“RRS at baseline and Week 12 and change in RRS were significant predictors of both survival and clinical worsening-free survival,” the team wrote. “These data support the long-term predictive value of the RRS in a controlled study population.”