Risk Assessment Tool Determines Efficacy of Selexipag in Patients with PAH

Raymond L. Benza, MD, FCCP

A post-hoc analysis of the GRIPHON study utilized the non-invasive risk assessment tool REVEAL Lite 2 (RL2) to assess the prognostic and predictive value in patients with pulmonary arterial hypertension (PAH) who were treated with a selective IP prostacyclin receptor agonist selexipag.

The investigators, led by Raymond L. Benza, MD, FCCP, Temple University School of Medicine, Philadelphia, Pennsylvania, found that selexipag treatment improved risk profile and long-term outcome compared with placebo.

They also considered RL2 risk category and change in risk category to be prognostic for long-term outcomes of patients with PAH.

The data was presented at the CHEST 2021 Annual Meeting during session, “Reveal Lite 2 Risk Assessment in Patients with Pulmonary Arterial Hypertension from the Griphon Study: A Post-Hoc Analysis Demonstrates Association of Risk Status with Long-Term Outcomes”.

The Methods

During the analysis, the RL2 tool was used to calculate risk score, and patients were categorized into low, intermediate, and high-risk strata at baseline and post-baseline timepoints.

Benza and colleagues performed analyses to examine associations between risk category and change in risk category with long-term outcome as well as the treatment effect of selexipag on long-term outcome by risk category.

Additionally, hazard ratios (HR) and concordance index (C-index) were calculate using Cox proportional hazard model.

A proportional odds model was used to compare the change in risk category from baseline between treatment arms featured in the study.

The Findings

Benza and colleagues found that 41% of all patients in the study were low at baseline, while 25% were intermediate and 33% were high risk. They noted that proportions were similar between treatment arms.

Regarding selexipag treatment, hazard ratios were 2.09 for intermediate risk patients compared with low-risk patients and 5.38 for high patients compared to low-risk patients.

For placebo, hazard ratios were 2.41 for intermediate risk compared to low-risk patients and 3.50 for high-risk patients compared to low-risk patients.

C-index values for selexipag at baseline, 4, 6, and 12 months were 0.68, 0.74, 0.76, and 0.73, respectively, while c-index values for placebo were 0.65, 0.67, 0.66, and 0.70.

Investigators noted that change in risk category correlated with change in mortality/morbidity rate, and improvement in risk category correlated with a reduction in mortality/morbidity rate.

Additionally, selexipag was approximately twice as likely to improve patients’ risk profile than placebo and was also responsible for reduced risk of mortality/morbidity across all baseline risk categories.

Overall, Benza and investigators concluded that RL2 risk assessment was prognostic of long-term outcome in patients with PAH and was capable of detecting responses to treatments.

“Simple risk assessment tools may have utility for treatment monitoring and as an endpoint in PAH clinical trials,” the team wrote.