Oral, Parenteral, and Inhaled Agents in PH and PAH

Key opinion leaders discuss the respective use of oral, parenteral, and inhaled treatment in PH and PAH.


Hilary M. DuBrock, MD: PIXEL [Prostacyclin International Expert Panel] was developed to provide consensus recommendations regarding the use of oral prostacyclin therapy in patients with idiopathic and connective tissue disease—associated pulmonary arterial hypertension [PAH]. They used a combination of prognostic variables including functional class, hemodynamics, RV [right ventricular] function, NT-proBNP [N-terminal pro-hormone B-type natriuretic peptide] and BNP [B-type natriuretic peptide], hospitalizations within the last 6 months, and 6-minute walk distance to provide a recommendation regarding when to use oral prostacyclin therapy in these patients. They were consistent with current guidelines in that they recommended parenteral prostacyclin therapy for any patients with functional class IV symptoms or patients with a high-risk hemodynamic profile.

Otherwise, oral selexipag was recommended to be used as an add-on therapy to a phosphodiesterase-5 inhibitor or endothelin receptor antagonist in patients who had other high-risk features, such as functional class III symptoms, an intermediate hemodynamic profile, abnormal RV function, an elevated NT-proBNP, or reduced 6-minute walk distance. This was rather consistent among patients with both connective tissue disease—associated pulmonary arterial hypertension and idiopathic PAH. Lastly, they did not recommend the use of oral treprostinil as an add-on therapy in patients with idiopathic or connective tissue disease–associated pulmonary arterial hypertension.

Charles D. Burger, MD: When discussing the possibilities of treatment with patients, immediately we talk about 3 different targets: the endothelin, nitric oxide, and prostaglandin pathways. We also talk about method of delivery. What do I mean by that? There are some oral medications; there are some inhaled medications. There are some medications that require continuous infusion with a pump, connected to a catheter that is indwelling in a large vein, generally in the neck or shoulder; and there are some medications delivered subcutaneously as a needle that lives just under the skin. Immediately, the patients say, “I’ll take a pill.” Of course, that makes a lot of sense from their perspective. They would much rather do that and we’re very empathetic to that, but it may not be the correct choice. You really have to focus on how sick the patient is, how bad their symptoms are, and how limited they are physiologically. Are they able to do activities of daily living?

We use markers to measure heart function and the severity of the pulmonary hypertension [PH] with a 6-minute walk to see what their physiology and exercise capacitance is. Of course, echocardiography and right-heart catheterization can bolster that information. If the patients are mildly or moderately ill, then oral medications might be a great choice as they would be more convenient for the patient and have less impact on burden of therapy that might lower their quality of life.

If patients are more ill, either in a high intermediate-risk or high-risk setting, you have to press on to the more complex therapies, particularly the infusion therapies, because those are the therapies that are the most potent and can turn the disease around quicker. Hopefully, if they have an excellent response, you may be able to circle back to the possibility of replacing those infusion therapies with oral therapies. Of course, patients are anxious to do that if it’s possible. But you really have to make the best recommendation that has the optimal chance for reversing the disease, improving their symptoms and their functional status. Because that has more impact on quality of life than the convenience of how patients take the medication.

Derek van Amerongen, MD, MS, FACOG: Over the last few years, we’ve seen a real profusion of various types of treatments across so many conditions. We have both IV [intravenous] therapies and oral therapies. Now we have subQ [subcutaneous] therapies. When you look at many of the guidelines, especially in complex areas such as PAH or oncology, you’ll see that treatment begins with an IV therapy, then it moves to a subQ therapy, and then you use an IV and an oral therapy. We have to be prepared on the health plan side to understand the entire treatment paradigm and to get away from this idea that was always very artificial in my mind, that there is something different about a medically administered drug, one administered by a healthcare professional, versus a self-administered drug.

When I was in clinical practice for many years, I thought a drug was a drug. Some were IV, some were oral, and some were subQ. If we’re going to understand the holistic treatment paradigm and make sure that we’re meeting the needs of clinicians, and certainly the needs of patients, we need to be somewhat agnostic regarding the route of administration, the frequency of dosing, and things of that nature. Certainly, one of the things that health plans will continue to do is have medical benefits and pharmacy benefits. But that is somewhat of an artificial construct. That just tells you which bucket you pull the dollars out of. From a policy standpoint, we’re trying to understand, how do you treat PAH? How do you treat PH? What is the logical sequence of drugs? That’s where it’s important to have visibility over all of the types of drugs that might be used, regardless of route of administration, frequency of dosing, etcetera.

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