2-Year Study of Riociguat as CTEPH Treatment Identifies Predictive Disease Markers

Recently published data from the CHEST-2 clinical trial showed that riociguat (Adempas) is both safe and effective as a longer term treatment of chronic thromboembolic pulmonary hypertension (CTEPH). The study also identified two predictive biomarkers distinguishing CTEPH and pulmonary arterial hypertension (PAH), and their concentrations serve as prognostic guides of disease progression and severity.

CHEST-2 was an open-label extension study in 237 patients with inoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (removal of a blood clot from vessels in the lung). All had taken part in CHEST-1, either in the placebo (control) or experimental arm. In the extension study, the patients were given riociguat at individually tailored doses for at least two years.

Outcomes, measured by researchers at the Bicêtre Hospital at Paris-Sud University, found that the overall survival at two years was 93 percent, and progression-free survival was 82 percent.

While the trial’s main focus was safety and tolerability, it also explored associations between survival and clinical worsening and markers of disease severity, such as the 6-minute walking distance test, plasma concentrations of NT-proBNP (N-terminal pro-type B natriuretic peptide, a prohormone used as a tool to stratify disease severity in PH), and WHO functional class.

Investigators discovered that the 6-minute walking distance test and NT-proBNP levels were predictive markers of overall survival, both at study’s start and at follow-up measurements. They also found that changes in walking distance times between the two time points could be linked to overall survival. This association differs from studies on pulmonary arterial hypertension, which could not link changes in 6-minute walking distance to survival rates.

WHO functional class was not associated with overall survival, but was linked to progression-free survival.

The trial did not reveal any new safety issues, but 54 percent of the patients experienced severe side effects. Of these, only 6 percent stopped the treatment due to adverse effects.

The findings are described in the study, “Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension: data from the CHEST-2 open-label, randomised, long-term extension trial”, and was published in the journal The Lancet Respiratory Medicine.