Treprostinil shows lasting benefits for children with lung-related PH
Study: Measures of disease severity, heart function showed improvement
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Treatment with treprostinil, a medicine that relaxes blood vessels, led to significant and sustained improvements in children with pulmonary hypertension (PH) caused by different lung conditions, according to a retrospective analysis.
Findings from the analysis were detailed in the study, “Treprostinil Is Associated With Early and Sustained Improvement in Group 3 Pulmonary Hypertension and Right Ventricular Function in Children,” published in Pulmonary Circulation.
Treprostinil mimics key molecule
PH comprises a group of disorders marked by high blood pressure in the pulmonary arteries, the blood vessels that transport blood from the heart to the lungs. High pulmonary blood pressure compromises oxygen delivery to the body and strains the right side of the heart, increasing the risk of heart failure.
There are several possible causes of PH, including left-sided heart disease, lung diseases, chronic exposure to low oxygen levels, blood clots, certain medications, or genetic factors.
Treprostinil is a medication used to treat various forms of PH by mimicking prostacyclin, a molecule in the body that relaxes blood vessels. It’s approved in various formulations for adults with pulmonary arterial hypertension. Inhaled forms are also approved for adults with pulmonary hypertension associated with interstitial lung disease.
However, the effects of treprostinil in children with PH caused by other underlying lung diseases are not well understood.
Proportion of patients with severe PH dropped from 48% to 12%
To address this gap, researchers at Stanford University in California examined the medical records of 41 children (56% male), ages six days to 15 years, with PH caused by various lung diseases. All began treatment with treprostinil, administered by subcutaneous (under-the-skin) infusion, between 2006 and 2022.
In most children (63%), PH was driven by bronchopulmonary dysplasia, a chronic lung disease caused by long-term ventilation and oxygen use at birth. In 10% of cases, it was caused by lung hypoplasia (lung underdevelopment), and in another 10% by congenital diaphragmatic hernia, a hole in the muscle that separates the chest and abdomen.
At the time treprostinil was started, most patients were already receiving supplemental oxygen, Revatio (sildenafil), and inhaled nitric oxide.
Over a median follow-up period of 13 months, 18 patients (44%) died, mostly due to lung failure, and one underwent a double lung transplant. The median NT-proBNP levels, a blood marker of disease severity, were nearly 50 times higher in non-survivors than in survivors (5,400 vs. 111 picograms per milliliter).
Echocardiogram measures of PH severity all improved over the study period, with the most notable changes occurring immediately after treprostinil treatment began. The proportion of patients with severe PH decreased from 48% to 12% immediately after treprostinil initiation, and this improvement was sustained for up to six months.
Similar results were observed for other measures of disease severity, including right ventricle hypertrophy (enlargement of the heart’s right ventricle, or lower right chamber) and NT-proBNP values.
Despite the [variability] of associated lung diagnoses, initiation of [treprostinil] was associated with an early and sustained [short-term] improvement in PH severity and [right ventricular] function by echocardiography.
Measures of right ventricular systolic function, or how well the right ventricle pumps with each beat, also improved over the study period. The proportion of patients with moderately or severely depressed right ventricular function decreased from 23% to 6% immediately after treprostinil was started, and to 3% after three to six months of treatment.
Treprostinil was not associated with worsening oxygenation over the first 48 hours of therapy in most patients. Low blood pressure or the need to increase doses of blood pressure and heart-support medications were uncommon during that period.
Within the first month of therapy, five patients (12%) developed new thrombocytopenia, or low levels of platelets, the small cell fragments that help blood clot. Even so, none of them experienced clinically significant bleeding.
One patient developed abdominal pain and vomiting in the first 48 hours of therapy, requiring a dose reduction followed by a dose reescalation, which was well tolerated. Another patient experienced flushing in the first 48 hours. No patients discontinued treprostinil during the study.
“Despite the [variability] of associated lung diagnoses, initiation of [treprostinil] was associated with an early and sustained [short-term] improvement in PH severity and [right ventricular] function by echocardiography,” the researchers wrote, adding that more studies will be needed to evaluate the responses of these patients to treprostinil.
