Shifting the Treatment Paradigm of Severe Asthma With Novel Biologics - Episode 5

Current Treatment for Severe Asthma

June 21, 2021
Reynold Panettieri, Jr, MD, Robert Wood Johnson Medical School

Sidney Braman, MD, Icahn School of Medicine

Geoffrey Chupp, MD, Yale School of Medicine

Nicola Hanania, MD, MS, Baylor College of Medicine

A review of the current available treatment options for severe asthma and a look into the GINA/NHLBI guidelines.

Reynold Panettieri Jr, MD: We heard a lot in that first segment, but we’re going to transition to currently available therapy. This is really important because this landscape has changed remarkably. Sid, you’re going to take this first question. What did the GINA [Global Initiative for Asthma] and NHLBI [National Heart, Lung, and Blood Institute] guidelines recommend for the treatment? What are the current therapies?

Sidney Braman, MD: Had you asked me this question 30 years ago, I would probably be giving you the same answer I am today. Clearly the foundation of treatment for asthma is inhaled corticosteroids [ICSs], as it was back then. We’ve had some nuances, which we’ll discuss. But also, we’ve sort of forgotten those guidelines. In addition to the approach of treatment, and while you’re doing it, you need an objective measurement. You need that environmental control as part of the whole treatment package. Certainly, we know about the pharmacological treatments: the inhaled corticosteroid and then adding on. Plus the partnership you get with the patient, hoping they’ll understand their disease, understand why they’re taking the medication, and understand the potential adverse effects. Some of the most brilliant things that occurred in those early guidelines, which persist even today, are the concepts of step-up therapy and minimal persistent inflammation. I’m not going to delay this, but I was amazed when I was a young fellow or a young faculty member and there was a study showing inhaled corticosteroid and bronchial biopsies, and most of those eosinophils melted away in 3 months. But not all of them. There was continued inflammation, and this is something we’re constantly telling our patients, even if they’re feeling better: Use inhaled corticosteroids. So that step up and step down is probably 1 of the most important contributors to the asthma field by these guidelines.

Reynold Panettieri Jr, MD: You hit a really important point, and certainly the step-wise approach is the dynamic approach. Nic, I’d like you to comment on this: Failure to step down, and the step down, can occur when you add a new intervention, like a biologic, that’s effective. Are you stepping down therapy or are you looking at this dynamic approach bidirectionally?

Nicola Hanania, MD, MS: Absolutely. Stepping down is certainly harder to do. Stepping up, you can throw the kitchen sink on the patient and see what happens. We tend to forget that with inhaled steroids—I agree with Sid, they still are the magic for asthma. At the same time, there are dose-dependent adverse effects. So if you have somebody on high-dose inhaled steroid, or even worse, oral steroid, then you definitely need to step down. How often? Every 6 to 8 weeks, you have to assess asthma control. You look at lung function. I don’t like to step down by looking only at symptoms because some patients may have poor perception of airway obstruction. I usually like to look at spirometry as well as asthma control before stepping down. I usually step down the inhaled steroid dose first. Although if you look at the guidelines and FDA, they suggest maybe even stepping down on the LABAs [long-acting beta-agonists] if they’re added to an inhaled steroid.

That would be my next step after stepping down the inhaled steroid. But I’ve rarely ever taken them off inhaled steroids, unless they have very mild asthma that’s seasonal. As an asthma specialist, I don’t see those patients, but they do exist. Some patients may not need inhaled steroids year-round, and this is maybe even more true in younger patients—in pediatrics as well—who they can use inhaled steroids only in the season when asthma flares up. 

We’ve done some changes. The NHLBI also released its latest reiteration of the guidelines recently. I agree with Sid that things haven’t changed too much, but 1 of the things that has changed is pushing the envelope of using as-needed inhaled steroid with a rescue medication, rather than a regular inhaled steroid in the milder population. I don’t think the jury is set on this, but it’s something that’s relatively new, and we’re looking at how to implement these strategies.

Reynold Panettieri Jr, MD: That’s a beautiful segue to the next question. We talked about controllers and relievers and relievers and controllers. Geoff, how about you describe the new world. We get a fuzzy boundary, right? What do you think? How do you define controller reliever?

Geoffrey Chupp, MD: What Nic has raised is creating a lot of complexity in the United States for multiple reasons. No. 1 reason is it’s a bit of a step away from a personalized approach to patients. It may be lumping together individuals who have very mild disease, who just need a reliever medication—classically, albuterol. Used on an as-needed basis, individuals who have more persistent disease don’t flare and have normal lung function. They have risk of flares, which require systemic steroids. Of course, for that group—it’s a very interesting approach—ICS long-acting beta-agonists are a good thing. 

The other thing is that there’s going to be some slow uptake in the United States because of insurance companies. I’m not sure it’s going to be easy for patients to get ICS LABA as a rescue therapy in this country at this point in time. It’s going to take a long time for us to retrain physicians and patients on this approach, so there are some complexities to this. I believe that GINA has allowed for the classic approach. They have both the preferred approach, as well as an alternative approach, which is still what we classically use: albuterol for rescue, inhaled steroid for control, and then step-up-therapy to LABA–LAMA [long-acting muscarinic antagonist] triple therapy, and then biologic therapy and systemic corticosteroids. But probably on the horizon is a better ICS bronchodilator, which is an ICS–SABA [short-acting beta-agonist]. This is probably what we should have in the clinic for patients who require frequent or systemic ICS use or have risk of flares. We have a little more work to do in this category, but that’s my answer to the question.

Reynold Panettieri Jr, MD: This whole concept of as-needed use of an ICS, an ICS LABA or SABA, is really interesting. You know what it’s really embracing? What our patients already do. We believe patients use controllers less as we prescribe them, but let’s be honest, they’re doing this approach already because the moment they get their disease under control, many of my patients say, “I don’t need this medication. I down dose.”

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Transcript Edited for Clarity