Shifting the Treatment Paradigm of Severe Asthma With Novel Biologics - Episode 8

Pathway Efficacy in Asthma Management

June 28, 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 panel of experts discuss the use of dupilumab for moderate to severe asthma and if one pathway has better efficacy in the management of asthma over another.

Reynold Panettieri Jr, MD: Sid, we’re going to ask you to comment on dupilumab [Dupixent]. Dupilumab was interesting because it came to use vis-à-vis atopic dermatitis. This is a drug that got approved for an indication, and the second indication was asthma. Where do you pull the trigger on dupilumab?

Sidney Braman, MD: As you said, atopic dermatitis was the first indication at the time when the drug was released and used, with great success. I’ve had a number of patients who’ve had both asthma and atopic dermatitis, and this is certainly where that drug is targeted. It has excellent effect on exacerbation rates and reducing exacerbation rates. It can be seen improving quality of life, and so forth. The thing about dupilumab is that it’s the only biologic that has been approved for auto-corrective steroid reduction. If needed, it can reduce your oral corticosteroid need. So that’s an area you might think about. 

One of the unusual things about dupilumab that should be mentioned—Geoff had mentioned the eosinophil count—is that most asthmatics are in the hundreds or so. If you see a patient who has an extremely high eosinophil count—over, let’s say 1000 or 1500—that’s probably not typical asthma, or at least you should consider the possibility that you’re dealing with something else. For example, vasculitis—the old Churg-Strauss vasculitis, which we now call EGPA [eosinophilic granulomatosis with polyangiitis]—certainly would be 1 consideration where mepolizumab, the anti–IL-5, would be indicated and not dupilumab.

Dupilumab, in these high levels of use intervals, actually has been shown to increase eosinophils, so it’s certainly part of the armamentarium for the T2 asthmatic. Especially in severe cases, it improves exacerbations and lung function symptoms, and it’s becoming more and more used by that group of patients. By the way, it also has an indication for nasal polyposis, as does omalizumab [Xolair] more recently, so there will be another indication or another group of patients whom you certainly would want to target.

Reynold Panettieri Jr, MD: You hit a very important point: Many of these drugs started in the asthma space, but they’ve quickly spread to other comorbidities. Frankly, when we use the drugs, we notice that people regain the sense of smell and taste, so there was a lot of crossover, which is certainly refreshing, but it also offers opportunity for patients with comorbidity before starting to choose which biologic is really going to hit that mark. It’s very important. Dupilumab—although it was going to be really focused on the IL-4 alpha receptor that integrates both 13 and 4 signals—was found to also work with high use. In fact, it worked a little better with the higher use, so the more the T2 signature, the more likely you’re going to be a responder. Now, the anti–IL-5s also have been approved for oral corticosteroid [OCS] sparing. The 1 that hasn’t been approved but has been shown in the real world is the anti-IgE, or omalizumab, that has affected OCS sparing but is not in its label. 

Nic, coming back to you, how do you determine which pathway is best for a patient? We just heard about 5 very effective drugs, and we know what they all do and how they’re partitioned. Give me your strategy on how you sequentially use these drugs.

Nicola Hanania, MD, MS: So, it’s always a clinical strategy—I wouldn’t say dilemma—that we have to make. As you can see, all the biologics we have are approved for T2-high asthma, whether it’s allergic or nonallergic. Phenotyping is important. I do certain tests in allergic asthma and noneosinophilic. I tend to use anti-IgE. However, in patients with eosinophilia and nonallergic asthma, we have a choice of an anti–IL-5 or an anti–Il-4—a receptor like dupilumab or the anti–IL-5 agents—and here, there are lots of other things that go into the equation. 

We tend to forget the patient, but we shouldn’t. There’s definitely a shared decision-making with the patient. Patients need to know what they’re stepping into. There may be insurance issues or coverage issues, and the frequency of administration plays a role—whether I want to give it at home or in the office—so there are several things other than the drug itself. Of course, the 1 I’m most comfortable with is what I would recommend, but there’s also patient preference, which tends to overlap. If you have a patient with high eosinophil levels and allergic asthma, there’s a potential for any of these agents to work. As we’ve shown, we have dupilumab in allergic patients with allergic rhinitis as well as with allergic asthma. We know that there’s a huge effect on the IgE production by blocking IL-4, but we also have shown that anti-IgE can work in allergic asthma as well. 

There’s a potential choice: 1 is given every 2 weeks at home, and omalizumab depends on the IgE level, maybe to be given every 2 weeks but sometimes every 4. It’s approved for home, but initially we only had the choice of giving it in the clinic. All these considerations have to be weighed in. It’s actually a journey when you start a biologic on your patient. It has to involve the patient, and it cannot be a 1-way street; we need the 2-part. Of course, we make sure his or her insurance covers the drug we want to start on. These are not cheap medications, as you know.

Reynold Panettieri Jr, MD: I love the idea and the highlight there on shared decision-making. We shouldn’t be solely making the decision. We need to engage the patient. The patient needs to be a partner in this, because it’s truly a legacy and a journey that they start. Now, I get impatient because I want to make people better. How long should I stay on a drug before switching, because I have choices? If we go back 12 years ago, we had 1 biologic, and we tried to fit that round peg in the square hole, so we could give them the biologic. We knew that it probably wasn’t effective because the best patients are those who respond, and we should really use biomarkers. Geoff, I’m curious, when are you going to throw in your hand and go to the next biologic? Do you have any guidance?

Geoffrey Chupp, MD: In terms of switching biologics, we have to give it enough time to work. Usually, we follow up the patients within 3 months after they initiate the treatment, and we get a sense of their response. Sometimes it’s very dramatic, and there’s no question the patients respond to the drug: Their flaring has stopped, their symptoms are improved, their lung function is better. I’ve been called by patients within weeks or days after starting biologics, saying, “I haven’t felt this good in years.” But then there are also other patients for whom it takes more time. They may be at the tail end of a flare, their disease is just somehow more resistant, it takes more time to respond, their phenotype is more complex, or they don’t flare as frequently—so 2 or 3 times a year. You need to track them long enough to get a real understanding of whether they’re really responding to the drug. That usually can take up to 6 months for other patients, so that’s generally our approach.

Reynold Panettieri Jr, MD: I agree. Patients want a guide. They want a guidepost. They want to know, “How long am I going to be on this?” Try to outline as best you can. Of course, there’s a lot of variance, but you’ve got to have some idea and some milepost saying, “At 3 months, we’re going to pivot, and we’re going to pivot because we haven’t hit these targets.” That’s an important aspect too. Sometimes the anti–IL-5s are very effective in obliterating the eosinophil count, so maybe we can make decisions swifter with those drugs and then switch over. But a drug like omalizumab is going to take 4 months to really have an impact on the disease process, depending on where you’re at. I like to have an on-deck circle, a batter who ready to go when that first batter either gets to first base or strikes out, and then they’ve got to be ready to go back into the next 1. I don’t typically wait or pause. My own experience is that I switch these in cadence. I don’t think there needs to be a washout when you switch biologics.

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Transcript Edited for Clarity