Time from PAH diagnosis impacts prognosis, response to selexipag

In a post hoc analysis of the GRIPHON study, patients with newly diagnosed pulmonary arterial hypertension had a worse prognosis compared with those with a longer time from diagnosis.

In addition, the benefit of selexipag (Uptravi, Janssen) was more pronounced in patients who were treated earlier compared with those treated later, according to data published in Chest.

“The benefits of prostacyclin pathway agents are well documented, yet administration often is delayed, and a significant proportion of patients never receive a drug targeting this pathway,” Sean P. Gaine, MD, director of the National Pulmonary Hypertension Unit and consultant respiratory physician at Mater Misericordiae University Hospital in Dublin, and colleagues wrote. “Selexipag, a selective prostacyclin receptor agonist, provides an opportunity for early targeting of the prostacyclin pathway with an orally available medication.”

GRIPHON was a global, double-blind, randomized, placebo-controlled, event-driven, phase 3 study that evaluated the safety and efficacy of selexipag in 1,156 patients with PAH. Patients were randomly assigned to selexipag or placebo twice daily. For the post hoc analysis, patients were categorized by time of diagnosis: 6 months or less (n = 404; 207 assigned selexipag and 197 assigned placebo) or more than 6 months (n = 752; 367 assigned selexipag and 385 assigned placebo).

The primary outcome was first morbidity or mortality event by time from diagnosis. Morbidity events were defined as disease progression or PAH worsening resulting in hospitalization, initiation of parenteral prostanoid therapy or long-term oxygen therapy, or need for lung transplantation or balloon atrial septostomy.

Newly diagnosed patients had poorer long-term outcomes than patients who were diagnosed for longer.

the percentage of patients with a morbidity or mortality event in the newly diagnosed group was 50.3% with placebo and 27.5% with selexipag and in the group with a longer time from diagnosis was 37.1% and 26.7%, respectively. Disease progression and hospitalization for PAH worsening were the most common events.

Selexipag reduced the risk for morbidity and mortality events compared with placebo, regardless of time from diagnosis. Selexipag reduced the risk for morbidity or mortality events by 55% (HR = 0.45; 95% CI, 0.33-0.63) in patients with newly diagnosed PAH and by 26% (HR = 0.74; 95% CI, 0.57-0.96) in those with a longer time from diagnosis (P = .021).

In the newly diagnosed group, 23.7% of patients assigned selexipag and 16.3% assigned placebo discontinued treatment compared with 26.9% and 17.1%, respectively, in the group with a longer time from diagnosis.

“These results highlight the potential benefits of early addition of an oral prostacyclin pathway agent to a patient’s treatment regimen,” the researchers wrote.

These data were previously presented at the American Thoracic Society International Conference in 2019. Read Healio’s previous coverage here.