Though the prostacyclin-targeting therapy selexipag is beneficial for PAH patients, investigators advise treatment to a trio of pathways.
The benefits for selexipag (UPTRAVI) in patients with pulmonary arterial hypertension—in which the therapy targets care through the prostacyclin pathway—are highlighted by a series of pivotal findings from the GRIPHON trial.
Though selexipag drives very positive outcomes in at-need PAH patients, it may best serve as complementary therapy. In an interview with MD Magazine® while at the American Thoracic Society (ATS) 2019 International Meeting in Dallas, TX, Rich Channick, MD, director of the Acute and Thromboembolic Disease Program at the UCLA Medical Center, and Prof. Sean Gaine, Director of the National Pulmonary Hypertension Unit in Ireland, defined the various pathways targeted by PAH therapies, and how multiple therapies in a patients’ regimen attack them all.
MD Mag: What is the optimized care pathway for pulmonary arterial hypertension?
Gaine: Well, what we've learned recently we have 3 pathways we treat in pulmonary hypertension. We have PD5 inhibitors, like sildenafil or tadalafil, endothelin receptor agonists, and prostacyclin drugs. And what we've learned is it's not just about treating 1 pathway at a time and working through it. It's actually about getting the patient early, usually start double up-front oral combination therapy now, like a PD5 inhibitor and an endothelin receptor agonist.
But what this data is showing us is if patients are not doing well, you should consider triple therapy for those patients. So we're getting more aggressive, I suppose, in the way we approach this. We still only have 3 pathways, and we've had 3 pathways for 20 years. But we're getting better at using these pathways, and understanding how to attack these pathways.
Channick: I think that's exactly right. I think that, getting back to what the GRIPHON trial showed in the original study, about 80% of the patients we studied were already on therapy—some other therapy. In fact, about one-third of patients were on 2 drugs. So for those patients, selexipag was their third drug. Even when we analyzed that, whether they had the background therapy or not, they still had the benefit for the primary endpoint.
I think that raises the point: in the case of pulmonary hypertension, we would believe more drugs are better—but in this study with an additional drug, you still see a treatment effect. As Sean outlined, in this specific subgroup that we looked at treating earlier, that seemed to be associated with good effect.