Including Uptravi early in PAH treatment lowers hospitalization risk
Effect strongest when started within 6 months of standard treatment
Adding Uptravi (selexipag) to standard-of-care therapy within six months of starting treatment may reduce the risk of hospitalization and disease progression in people with pulmonary arterial hypertension (PAH), a study found.
The study, “Early Addition of Selexipag to Double Therapy for Pulmonary Arterial Hypertension,” was published in JAMA Network Open. The work was funded by Actelion Pharmaceuticals, a part of Johnson & Johnson, which sells Uptravi.
PAH is marked by increased blood pressure in the vessels of the lungs, which puts strain on the heart. Standard treatment for PAH patients at low or intermediate risk involves a combination of two types of medicines that act to lower blood pressure: an endothelin receptor antagonist (ERA) and a phosphodiesterase type 5 inhibitor (PDE5i).
Uptravi works to mimic the activity of prostacyclin, a signaling molecule that prompts blood vessels to relax and widen, thereby reducing blood pressure. Current guidelines recommend adding Uptravi to standard-of-care dual therapy in patients whose condition worsens with standard care, but this requires regular follow-up assessments that can’t always be done in a timely manner.
“More practical guidance on the timing of the addition of oral [Uptravi] is warranted,” the researchers wrote.
Analyzing data
To provide that guidance, the scientists conducted an analysis of a U.S. claims database. The researchers identified data from nearly 3,000 people with PAH who were receiving standard double therapy, then compared outcomes between those who did or did not add Uptravi to standard treatment. A total of 351 patients ever received Uptravi. The most common, PAH-associated coexisting conditions were systemic (body-wide) hypertension and connective tissue disease.
Results showed that, compared with patients who used only standard treatment, those who started on Uptravi within six months of starting standard treatment were 18% less likely to be hospitalized and also 18% less likely to experience PAH-related disease progression.
“This comparative effectiveness study found that in commercially insured patients with PAH, adding oral [Uptravi] within 6 months of ongoing [double therapy] consisting of ERA and PDE5i in clinical practice was associated with decreased risk for all-cause and PAH-related hospitalization and for disease progression,” the researchers wrote.
The greatest reduction in risk of these outcomes was achieved when Uptravi was added to standard therapy within three months. For patients who started on Uptravi six to 12 months after starting standard treatment, there was no significant difference in these outcomes.
“Our findings suggest that a long delay (12 months) in adding oral [Uptravi] and substantial treatment gaps may contribute to suboptimal outcomes among patients with PAH,” the scientists concluded. “These findings suggest that the value of [adding Uptravi to standard-of-care dual treatment] may not be fully realized given that most patients in the dataset were never escalated to [adding Uptravi to standard-of-care].”
In a commentary published alongside the study, clinicians in Canada and the U.K. said that this work is “consistent with earlier studies that suggest the benefit of [Uptravi] may be time dependent, being most effective if introduced early, ideally within 6 months of initiating therapy with an ERA and a PDE5 inhibitor.”
The commentary highlighted limitations of the study, such as not having data about functional capacity and other clinical features “that are used to evaluate patients who are at risk of worsening and to inform decision-making, such as addition of new therapies or referral for lung transplant.” Also, only 37% of participants with PAH had shortness of breath, “the most common symptom in PAH, highlighting shortcomings of the dataset,” the authors wrote.
The analysis relied on data from a pharmacy claims database, so it didn’t include some clinical data that would normally help doctors decide whether or not it’s appropriate to initiate Uptravi. The scientists urged appropriate caution in interpreting the findings.
The authors also lamented that the study doesn’t help clinicians who are figuring out how best to use Winrevair (sotatercept-csrk), a more recent PAH therapy sold by Merck that was approved in the U.S. and Europe earlier this year.
“As clinicians treating patients with PAH, we are also left with addressing the therapeutic elephant in the room: specifically, how [Winrevair] will be incorporated into practice relative to other add-on therapies,” they wrote.
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