Treatment Selection for Severe Asthma

Raffi Tachdjian, MD, MPH, FAAAAI, FACAAI: It’s great that our field finally has this many choices as we try to get toward precision medicine and individualized therapies, so that it’s not just corticosteroids for all comers. Before we dive into the granular level, Dr Chase, take us through your decision process for treatment selection for eosinophilic or allergic asthmatics who are in that severe asthma category.

Nicole Chase, MD, FAAP, FAAAAI, FACAAI: I try to guide a lot of my treatment decisions based on shared decision-making with the patient. Specifically, what are their limitations? One thing I focus on is what’s going to get this patient to want to take their medication. It’s not just that I want them to take their medication. What’s important to them? For example, for a patient who otherwise has exertional dyspnea or exertional-induced coughing or wheezing, the stepwise approach following the guidelines is easy to start with in terms of when we get into those higher-level categories. I think less about these as separate allergic and eosinophilic and more about the patient’s endotype, and I look to the biomarkers to guide treatment.

In terms of treatment plans, I ask patients about their specific symptoms. If it seems there’s another variable playing a role in their asthma, we try to address that. If they have gastroesophageal reflux, we may try to address that to minimize other reasons for their asthma to flare. We do the same thing with allergic rhinitis. If their asthma seems to be more seasonal, we’d think about initiating allergen immunotherapy if they’re stable enough to do that. Once we’re at the end of the line, we’re thinking more about biologics. That’s when we use the endotype to stratify. If someone is truly allergic only, they have IgE, their eosinophil count is repeatedly low, given that we know that can change on a regular basis and they don’t have elevated levels of exhaled nitric oxide, then something like omalizumab might be a reasonable option. If they wouldn’t otherwise tolerate allergen immunotherapy, then it makes a lot of sense.

A subset of patients is predominantly eosinophilic asthma. These tend to be the adult patients, late-onset. We haven’t seen them and followed them for a long time as children. They may have some component of sinus disease as well. For those patients, you can target the eosinophils or think about targeting both disease processes in the upper and lower airways. We’ve all seen patients who have sinus disease and nasal polyposis, where it’s the unified airway—the inflammation in the upper sector triggers the inflammation in the lower sector of the airway. We have to lean on those biomarkers and decide what makes the most sense.

Finally, we talk with patients about their preferences. We’re at the point where all our biologic therapies are injectables. There’s a conversation to be had: “What do you think about this? This is a totally different way of treating asthma from how we’ve ever treated you before.” Then we decide with the patient—talking through risks, benefits, adverse events—based on what they feel would be reasonable. It’s a stepwise approach, and it’s a lot of asking and data gathering from the patient, then taking that information, processing, and presenting the next set of questions to guide the therapies. It’s an art form for sure, as I’m sure you’re all well aware.

Raffi Tachdjian, MD, MPH, FAAAAI, FACAAI: It’s tedious and time consuming, nonetheless. Thank you for that. Dr Siri, are there any other immune-mediated conditions that go through your mind that you want to take into consideration as you’re coming down the treatment highway?

Dareen D. Siri, MD, FAAAAI, FACAAI: Yes. In designing the treatment plan, it’s important to consider immune-mediated diseases. For example, Dr Chase was talking about chronic rhinosinusitis [CRS] with nasal polyps. A lot of patients have these other immune-mediated diseases, such as allergic rhinitis, asthma, eosinophilic esophagitis, or food allergy. They may also have atopic dermatitis. And a lot of these are underscored by inflammation, particularly type 2 inflammation. If we think about treating things in terms of that overlying aspect, then perhaps we can target those additional therapies. If we control those other diseases, that can be helpful in controlling their asthma or vice versa. This may require us to collaborate with other specialists—gastroenterologists, dermatologists.

We also have to think about other immune-mediated diseases, like immunodeficiency. With genetics and things like that, some patients have variable penetrance. If a patient has immunodeficiency, that doesn’t mean they can’t also have moderate to severe type 2 inflammatory asthma. We see this overlying thing, with a lot of patients who have multiple immune-dysregulated diseases. That’s an important immune-mediated disease to think about in terms of the treatment plan. Collaboration is super important. Controlling things like CRS with nasal polyps is a huge factor in terms of unified airway disease. If we’re controlling that, perhaps we’re controlling this too.

Transcript edited for clarity