Adjusting Endothelin Receptor Antagonists for Real-World PAH Patients


Now that real-world data registries are being compiled, the constriction-limiting drug class is now going through personalizations including new titration strategies.

It was only a few decades ago when Gary Palmer, MD, MBA, could recall pulmonary arterial hypertension (PAH) serving as an alternative death sentence.

While at the 2018 CHEST Annual Meeting in San Antonio, TX, the Vice President of Medical Affairs for Actelion Pharmaceuticals recalled how patients diagnosed with the rare, chronic condition had little option or hope for resolution. That's since changed, since the endothelin receptor antagonist (ERA) drug class has reached the market in recent years, with capabilities to lessen blood vessel constriction and fibrosis.

But there's still work to be done. Palmer, along with Victor Tapson, MD, Director of the Venous Thromboembolism & Pulmonary Vascular Disease Research Program at the Cedars-Sinai Medical Center, sat down with MD Magazine® at CHEST 2018 to discuss how ERAs are now being personalized and tailored in response to real-world analysis and registry information.

MD Mag: What is the current state of advancing therapies for pulmonary arterial hypertension?

Tapson: We're very excited in the last 4-5 years to have several new drugs on the market for pulmonary arterial hypertension. One is macitentan, approved on a big study called SERAPHIN, and the other is selexipag, approved on a big study called GRIPHON. And these are revolutionary studies that added 2 new medications to our arsenal.

Palmer: As a company, we're expanding our understanding of this disease by doing what we call real-world studies, as well as clinical studies. In clinical studies, we control the conditions very carefully, we have inclusion and exclusion criteria, but what happens is these drugs get used in the real world with patients. The therapy gets individualized for each patient. We continue to collect data in registries, and the data we're presenting at this meeting coming out of real-world studies are the registries where we see what's actually happening in real practice. So, we see for instance on the data from macitentan, we're treating patients in a population with pulmonary hypertension, where many of those patients have been excluded from clinical trials in the past.

We see them being treated with macitentan, and the experience is good. The patients are responding nicely, and it's relatively safe in that population. And similarly with selexipag, in our base trials, we titrated patients once per week. And in real practice, we're seeing that titration sometimes occurs a little sooner than that. It takes 2 weeks, sometimes 3 weeks, before patients tolerate side effects and get titrated up. It's new and important information for physicians to see—things are a little different in real-world practice.

Tapson: You can't emphasize enough how important registries are. We need randomized trials to get drugs through the FDA, really well-controlled trials. Like Gary mentioned, in real world settings, things are done differently. Patients might be a little different, they may not be as rigorously screened in terms of inclusion criteria to be placed on a drug.

People worried about the endothelin receptor antagonists and liver problems for a long time. We had to check liver functions every month. Now, with our newer ERAs like macitentan, we don't need to do that. Furthermore, they're safe and effective, and proven safe and effective in patients with liver disease.

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