Newly Diagnosed Patients With PAH Benefit From Earlier Initiation of Therapy

Patients with pulmonary arterial hypertension (PAH) who are treated with selexipag within 6 months of their diagnosis had a reduced risk of morbidity/mortality compared with patients who were treated longer than 6 months after diagnosis, according to a study published in Chest.

Selexipag is an oral selective prostacyclin receptor agonist that targets the prostacyclin pathway. Because selexipag is an oral therapy, it does not need to be titrated to an individual dose nor does it have a complex administration, both of which are challenges with other agents targeting the prostacyclin therapy.

“The benefits of prostacyclin pathway agents are well-documented, yet administration is often delayed and a significant proportion of patients never receive a drug targeting this pathway,” the authors explained.

In a post hoc analysis of GRIPHON, a large, randomized controlled trial in PAH, 1156 patients with PAH were assigned randomly to receive selexipag or placebo. They were split into 2 groups at time of randomization: 6 months or less from time of diagnosis and more than 6 months from time of diagnosis.

In the overall study, GRIPHON demonstrated a 40% reduction in the risk of a primary composite outcome of morbidity/mortality with selexipag compared with placebo. After the study, all patients were categorized based on time from diagnosis. The time from diagnosis was used to define newly diagnosed patients who were treated earlier (≤ 6 months) and patients who were treated later (> 6 months).

The majority of patients (n = 752; 65.1%) were treated later. In general, patients treated when they were newly diagnosed were younger. The post hoc analysis found that among patients taking placebo, those newly diagnosed were more likely to experience morbidity/mortality even than patients diagnosed longer (50.3% vs 37.1%). However, among patients taking selexipag, the percentage of those who experienced a morbidity/mortality event was similar among the 2 groups (27.5% for newly diagnosed patients vs 26.7% for patients diagnosed longer).

Compared with placebo, selexipag reduced the risk of morbidity/mortality by 55% for newly diagnosed patients (HR, 0.45; 95% CI, 0.33-0.63) and by 26% for patients diagnosed longer (HR, 0.74; 95% CI, 0.57-0.96). The mean exposure time to selexipag was similar in both groups (76.7 weeks in newly diagnosed patients vs 76.3 weeks in patients diagnosed longer), while patients with a longer time from diagnosis had a longer exposure time in the placebo group (74.7 weeks vs 64.4 weeks).

A slightly higher percentage of patients with a longer time from diagnosis discontinued treatment with selexipag compared with newly diagnosed patients (26.9% vs 23.7%). Until the end of the study, 38 newly diagnosed patients on selexipag and 62 patients diagnosed longer on selexipag had died compared with 44 and 61, respectively, on placebo.

The authors noted that the results of the post hoc analyses confirm that newly diagnosed patients with PAH have a worse prognosis than those who had a longer time from diagnosis, but that the reduced risk of a morbidity/mortality event on selexipag was more pronounced in newly diagnosed patients.

“From a clinical perspective, these data indicate that, despite their poorer prognosis, newly diagnosed PAH patients can respond to and benefit from early targeting of the prostacyclin pathway with selexipag, adding to the body of evidence showing that newly diagnosed patients benefit from early initiation of therapy,” the authors concluded.

Reference

Gaine S, Sitbon O, Channick RN, et al. Relationship between time from diagnosis and morbidity/mortality in pulmonary arterial hypertension: results from the phase III GRIPHON study. Chest. Published online February 2, 2021. doi:10.1016/j.chest.2021.01.066