Adempas Is Effective in Infants with Chronic PAH: Study

The therapy has been linked with improved clinical outcomes, heart function in adults

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Infants with pulmonary arterial hypertension (PAH) who were put on Adempas (riociguat) after Revatio (sildenafil) and other therapies failed to control their symptoms showed improvements in lung and right heart function, according to data from a small study.

They also had a reduction in high blood pressure in the blood vessels that supply the lungs.

“With this case series we found a similar safety profile with superior efficacy of riociguat in comparison with sildenafil in a high acuity, high risk population,” the researchers wrote.

The study, “Safety and Feasibility of Riociguat Therapy for the Treatment of Chronic Pulmonary Arterial Hypertension in Infancy,” was published in The Journal of Pediatrics.

Adempas, marketed by Bayer in the U.S., is a soluble guanylate cyclase (sGC) stimulator approved for treating PAH and chronic thromboembolic pulmonary hypertension (CTEPH). It works as a vasodilator, meaning it induces widening and relaxing blood vessels.

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While Adempas has been linked with improved clinical outcomes and heart function in adults with chronic PAH, its effects on infants has been poorly studied and there’s “no established standard of care management approach” for infants with chronic PAH, the researchers wrote.

Testing Adempas’ safety and effectiveness in infants

Now, a team led by researchers at the University of Iowa and the University of Colorado evaluated the safety and effectiveness of Adempas in infants whose disease was not brought under control with Revatio, either alone or combined with other therapies.

The team screened a clinical database and identified 10 infants (ages 1–12 months) with chronic PAH who received oral Adempas, offered as an alternative medicine since January 2020.

All had failed to respond to first-line treatment with inhaled agents – nitric oxide (NO), epoprostenol (sold under several brand names) –  and began Revatio, either alone or in combination, as a second-line therapy. In cases where this also failed to completely control symptoms, they received Adempas.

Eligible participants were diagnosed with chronic PAH by echocardiogram and treated for a minimum of one week with Adempas.

The mail goal of the study was to assess the occurrence of severe hypotension (low blood pressure), defined according to two pre-established criteria: a decrease in the systolic (the pressure when the heart pushes blood out), diastolic (the pressure when the heart rests between beats), or the mean arterial pressure (the average pressure during one cardiac cycle); or the need to start or increase vasoconstriction medications following Adempas.

Adempas was started after a median of 170 days after birth and most patients were on combination therapy. The doses were gradually increased from 0.25 mg every 12 hours initially to 0.5 mg every eight hours. It took a median of 11.5 days to reach that target dose.

Most patients tolerated discontinuing Revatio well, except two who had a rapidly escalating oxygen requirement. These patients were put on a higher dose of inhaled NO together with epoprostenol inhalation and vasopressin (which increases blood pressure) to sustain oxygen levels.

During the study period, there were no episodes of critical hypotension and no patient required a new medication or a dose increase to control blood pressure.

All heart pressure parameters (systolic, diastolic, and mean arterial pressure) were reduced within two hours of starting Adempas, particularly with the first doses. The lessening of arterial pressure lasted from one dose to one week.

The patients’ respiratory function also improved with Adempas, as shown by a reduction in the mean airway pressure, fraction of inspired oxygen, and respiratory severity score. Pulmonary artery pressure (PAP) and the heart’s right ventricle (RV) performance also improved.

Side effects of Adempas

Gastrointestinal side effects were seen in two patients. One began to vomit more compared to the study’s start (baseline) and another had a single vomiting episode after the second dose. One patient with a pre-existing bleeding tendency had surgical site bleeding on Adempas. None of the side effects prompted discontinuing Adempas.

“Similar to adult studies, we demonstrated improvements in respiratory status, PAP and RV performance” following Adempas, the researchers wrote.

Compared with chronic inhaled NO, Adempas “may be beneficial in preserving cardiovascular function for infants awaiting long-term tissue repair via lung growth and/or lung transplantation,” they said.

The switch from Revatio to Adempas is a period of risk for worsening, however. As such, the team recommends that “co-administration of sildenafil and riociguat should be avoided and a washout period of at least one day should be allowed.”

A Conversation With Rare Disease Advocates