These findings from clinical practice were consistent with those reported in previous clinical trials, supporting the therapy’s favorable safety profile.
Data from EXPERT was reported in an article, “Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry,” published in the journal Respiratory Medicine.
Designed to widen lung blood vessels and reduce blood pressure, Adempas is approved for the treatment of adults with PAH and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH).
These approvals were based on data from two Bayer-sponsored Phase 3 clinical trials — PATENT-1 (NCT00810693) in PAH and CHEST-1 (NCT00855465) in CTEPH — and their long-term extension studies — PATENT-2 (NCT00863681) and CHEST-2 (NCT00910429).
Notably, Adempas was shown to be generally safe and to lower pulmonary vascular resistance — a parameter that reflects the effort required for blood to flow through lung arteries — lessen disease severity, and improve exercise capacity in PAH and CTEPH patients.
Bayer launched the four-year EXPERT registry (NCT02092818) to monitor Adempas’ long-term safety within routine clinical practice in 28 countries around the world. It recruited 1,330 people, including 326 with PAH, 956 with CTEPH, and 48 with other types of pulmonary hypertension (for which Adempas was used off-label).
“Registries provide important information about the safety of [therapies] in clinical practice, and thus supplement information gained from selected populations under the closely controlled conditions of clinical trials,” the researchers wrote.
In the current study, researchers focused only on data from PAH patients (234 women and 92 men, with an average age of 54 years), of whom 226 (69.3%) had idiopathic disease, or that of unknown cause. Patients included in the analyses had a median disease duration of 3.4 years, and nearly all of them (90%) had at least one simultaneous health condition.
Most people (77.9%) had been living with the disease for at least six months (prevalent disease) and more than half (55.8%) had been receiving Adempas for three months or longer before study entry (pre-treated group). Most of them were also receiving other PAH therapies, mainly endothelin receptor antagonists.
Participants were followed for one to four years from enrollment, or until 30 days after discontinuing treatment with Adempas. A total of 286 (87.7%) completed the study.
Results showed that 229 (70.2%) PAH patients experienced adverse events, with the most common being dizziness (11.7%), right-sided heart failure or heart failure (10.7%), swelling (10.7%), diarrhea (8.6%), shortness of breath (8.0%), and cough (7.7%).
Nearly half (46.6%) also had serious adverse events, with right-sided heart failure or heart failure (10.1%), pneumonia (6.1%), shortness of breath (4.0%), and fainting (3.4%) being the most frequently reported.
Notably, the most common adverse events “were consistent with symptoms of the underlying disease or with vasodilatation by [Adempas],” the researchers wrote, and those considered related to Adempas were reported in 15% of participants (with those classified as serious in 7.1%).
Less than 8% of patients discontinued treatment due to adverse events (7.4%) or serious adverse events (6.4%), with the most common being right-sided heart failure/heart failure and shortness of breath (1.2% each).
In addition, more participants receiving Adempas for less than three months before study entry (newly treated group) experienced adverse events (74.3% vs. 67%) and serious adverse events (54.2% vs. 40.7%), and discontinued treatment due to these events than those in the pre-treated group (11.8%–13.9% vs. 2.2%).
“These observations may be partly explained by a worse disease state … but also partly by more frequent measurements (e.g., of blood pressure) in the newly treated group,” the team wrote.
When given in combination with other PAH therapies, Adempas was associated with a slightly higher rate of adverse events than when it was administered as a stand-alone therapy (66.7%–74.3% vs. 61.4%).
Moreover, statistical analyses indicated that 94.2% of PAH patients were alive after one year of follow-up, 82.2% after two years, and 71% after three years. A total of 44 (13.5%) people died or experienced a fatal serious adverse event, with right-sided heart failure being the most common (2.7%).
One death was considered related to Adempas, with therapy-associated hemoptysis (coughing up blood) being complicated by the simultaneous presence of hereditary hemorrhagic telangiectasia (a blood vessel disease) and atypical pneumonia.
The team noted that simultaneous treatment with blood thinners or anticoagulant medications may have contributed to bleeding episodes in some cases, which occurred in 12.6% of the participants.
Further analysis estimated there were 6.2 events of low blood pressure and 5.5 hemoptysis/lung bleeding events per 100 patient-years — rates lower than those reported in the long-term extension PATENT-2 study, the team wrote. Of note, patient-years sum up the follow-up years of all patients included in the study.
“Final data from the EXPERT registry showed that in patients with PAH, the long-term safety of [Adempas] in routine practice was consistent with clinical trials, with no new safety concerns identified,” the researchers concluded.
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