Rationale for Step-up Therapy in Asthma

This is part of the MD Magazine^® Peer Exchange, “Precision Medicine in the Treatment of Severe Asthma.”Click here for Segment 12 and learn about biological therapy for the treatment of asthma.

Peter Salgo, MD: Somebody comes in and you want to step up treatment. Who are the folks who need it? How do you go about deciding what to do about it? Who gets treated and gets step-up therapy?

Raffi Tachdjian, MD: Step-up therapy, obviously, as we go back to the guidelines and our inner sense, is appropriate when you’re not achieving control or if someone is having periodic exacerbations and you’re going to focus on that period of the year. We talked about really attacking this hard and then backing off. It’s both helpful for the area under the curve of feeling better, of not having inflammatory asthma or inflammatory airways, as well as reinforcing our effect on the patient to gain some confidence and say, “Wow, I started feeling better the minute I walked out of that clinic.” And then we started stepping down.

David Rosenstreich, MD: If they’re still using their albuterol frequently, if they’re still symptomatic or are having exacerbations, you want to step up. You start with an inhaled steroid, a long-acting beta-agonist, and a muscarinic antagonist—triple therapy for these patients. You work your way up. And once you get to that point, if they’re still symptomatic, then we have new biologics.

Peter Salgo, MD: Which brings us to the targeted approach with the monoclonal antibodies. Here, we’re looking at attacking all these interleukins. What is the advantage of a targeted approach? Is there a targeted approach advantage?

Neal Jain, MD: Echoing what David had just mentioned, we have these step-up therapies. Unfortunately, what ends up happening in our patients is that as you step up, especially with the steroid dose, you have a risk for side effects and adverse effects. And that risk is not just limited to children, unfortunately. We are seeing that the higher the dose you get to, the more apt you are to having some of these adverse effects. As a result of that, in many cases, some of these patients end up being on chronic oral steroids at, sometimes, very high doses. And that obviously can be very deleterious. If we know the inflammatory pathways that are turned on, we’re getting to a point where we’re approaching what we’ve see in rheumatology and oncology. We know that this is the pathway that’s turned on. Let’s target that approach in a finite manner, where we’re not going to have those deleterious effects associated with the medications.

Peter Salgo, MD: It’s the difference between using a laser and a shotgun.

Neal Jain, MD: Absolutely.

Peter Salgo, MD: A lot less collateral damage.

Neal Jain, MD: Absolutely.

Peter Salgo, MD: This is exciting.

Raffi Tachdjian, MD: And that’s where steroid-sparing therapy is coming into the norm—into the community.

David Rosenstreich, MD: For someone who’s been in this field for a long time, this really is a revolutionary period. Probably, since the introduction of inhaled corticosteroids, this is really a chance to make an enormous difference in the lives of asthmatics.

Peter Salgo, MD: I think it’s fair to say, in so many areas of medicine, that there’s a real buzz out there. We’re not just blasting away, hoping to get some effect here, but ignoring or at least choosing to ignore the downsides everywhere else. So this is fun, isn’t it? This is fun.

Neal Jain, MD: Absolutely.

Raffi Tachdjian, MD: And until now, step-up therapy was just more micro-grammage, or grammage, or mili-grammage therapy.

Peter Salgo, MD: More of the same. If you’re getting to grammage, we’re in trouble.

Raffi Tachdjian, MD: Yes, exactly.

Neal Jain, MD: Without even knowing that they had T2 inflammation. We carry all our data. We have this population of asthmatics, some of whom have this T2 inflammation, and the majority of that group carries the average. Everyone has had this mentality that steroids work in everyone. Well, that’s not the case. Now we’re starting to understand, “Hey, this is T2 high. You are going to potentially respond to more steroids, but also we have these therapies that can target that inflammation.”

Transcript edited for clarity.