Results from the ongoing Phase 3 study known as CHEST-2 support the long-term use of riociguat in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The findings are detailed 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,” published in the journal The Lancet Respiratory Medicine.
Researchers investigated the effects of riociguat and how it impacted the association between markers of disease severity and long-term outcomes in patients with inoperable CTEPH, or with persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA, an operation to remove blood clots from pulmonary arteries in the lungs).
The team evaluated patients previously enrolled in the CHEST-1 clinical trial, now entering the CHEST-2 open-label extension trial (NCT00910429), where all are receiving an individual adjusted dose of riociguat (maximum dose allowed was 2.5 mg, three times a day). Researchers assessed not only safety and tolerability (CHEST-2 primary endpoints), but also markers of disease severity, including 6-minute walking distance (6MWD), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration, and WHO functional class. These were measured at baseline and at follow-up, accounting for overall survival and progression-free survival.
In total, 237 patients are enrolled in CHEST-2. Researchers registered 93% and 82% overall survival and progression-free survival, respectively, at two years follow-up. Additionally, they detected a significant association between 6MWD and NT-proBNP concentration and overall survival at both baseline and follow-up. WHO functional class at baseline and follow-up showed no significant association with overall survival, but was associated with progression-free survival.
Long-term riociguat use did not result in significant changes in adverse events compared to those previously described in safety profiles. In total, 129 patients (54%) experienced adverse events, and 14 patients (6%) discontinued therapy due these events.
Researchers concluded that the results support a safe and long-term use of riociguat in patients with CTEPH, and that both 6MWD and NT-proBNP concentration can act as good prognostic markers. The CHEST-2 study is expected to conclude in April 2019.
“A notable result of this study was that change in [6-minute walking distance] over 12 to 16 weeks of riociguat treatment was significantly associated with long-term overall survival and clinical worsening-free survival. This finding is in contrast to those from some studies of pulmonary arterial hypertension, where change in [6-minute walking distance] was not significantly associated with survival,” the study’s first author, Gérald Simonneau, MD, from the Assistance Publique–Hôpitaux de Paris and Service de Pneumologie in Hôpital Bicêtre, in France, wrote, according to a press release.
“These findings emphasize that pulmonary arterial hypertension and [chronic thromboembolic pulmonary hypertension] are distinct disease entities that might require different clinical assessments and treatment targets,” Dr. Simonneau concluded.