Payel Gupta, MD, allergist and immunologist at Ease Allergy Clinic and Mount Sinai.

Payel Gupta, MD

Biologic Selection in Severe Asthma: Biomarkers, Comorbidities, When to Switch

Selecting the right biologic for a patient with 

 is rarely straightforward. The growing number of available agents has expanded treatment possibilities, but it has also introduced new complexity into clinical decision-making. Clinicians must weigh biomarker profiles, overlapping comorbidities, and the practical constraints of insurance coverage—all before a patient ever takes their first dose.

Biomarkers have become central to that process. Total IgE, fractional exhaled nitric oxide (FeNO), and blood eosinophil counts each offer guidance on which mechanism of action is most likely to benefit a given patient. But the field is still far from a clean 1-to-1 mapping of biomarker to biologic, and the hope is that precision medicine will continue to close that gap as the evidence base matures.

Comorbidity burden adds another layer. Many patients with severe asthma also carry type 2 inflammatory conditions—atopic dermatitis, eosinophilic esophagitis, chronic rhinosinusitis with nasal polyps, and chronic spontaneous urticaria—and biologics approved across multiple indications can offer a meaningful clinical advantage in those cases.

Payel Gupta, MD, allergist and immunologist at Ease Allergy Clinic and Mount Sinai, spoke with 

 about how she navigates these decisions, from first-line biologic selection through reassessment when patients do not respond as expected.

 When you're selecting a biologic for severe asthma patients, what clinical or biomarker findings most reliably guide your first choice, and how has your approach to that decision changed over the past few years as the pipeline has expanded?

The choice of biologics really has changed over time. We know that certain indicators help us determine which biologics may work better for some patients rather than others, and we're really hoping to go towards precision medicine in this area. It's really exciting with all the research that's being done and what we're finding out.

Some of the biomarkers that we check are IGE level…FeNO…and blood eosinophil count, which can be a helpful biomarker. These are some of the biomarkers that we have right now, and hopefully, there will be others that will be available in the future.

 For patients who have an incomplete response to their first biologic, how do you decide between switching agents versus adding or adjusting therapy? Is there a timeline or threshold you use?

It really depends on the biologic that was initiated… the dosing frequency and…how the patient is doing. The data show that 10% of patients may not respond to the first biologic chosen. That’s because, even though we have some biomarkers to help us decide which biologic to use, oftentimes we're hindered in that choice also by what's covered by insurance. We may think that one biologic is going to work better for the patient than the other, but unfortunately that biologic that we would ideally like to use is not covered by the insurance company, and so we have to go with our less preferred biologic.

Essentially, we monitor the patient, and within a month to 2 months, if the patient is not doing better, we're usually looking to change the biologic and see if they may respond better to something that has a different mechanism of action.

 Are there specific patient phenotypes or comorbidity profiles where you've shifted how you think about biologic selection?

 [With a] higher total IGE level, somebody might respond better to omalizumab. Or if their FeNO is higher, we tend to think that they have more of that type 2-mediated asthma, and so that would [point toward] things like dupilumab.

As far as comorbidities go, there’s a lot of type 2 conditions that patients may have where certain biologics are also approved [for] that condition, and so understanding the full picture [is important].

Really paying attention to other factors, like if the patient also has eczema [or other comorbidities] can help us determine if we may want to pick 1 biologic over the other, because if they're approved for more than 1 of the patient's conditions, then we may be able to get a 2-for-1 with their medication and hopefully help them with both of their conditions, as opposed to just 1.

 How do you define treatment success once a patient is established on our biologic?

We look at several factors. We usually monitor things like the ACT and ARQ, which are objective questionnaires that we can use to see how a patient is doing between visits. We also look at their lung function testing. Has their FEV1 improved? In some patients [with] severe asthma, we may not see much of an improvement, but at least we should not see worsening of their lung function parameters. Obviously, ER visits [and] oral corticosteroid use are other factors that we monitor [to] make sure that the patient is doing better in those respects.

 What time frame do you give a drug efficacy evaluation?

Overall, you know, history is really important. We’re really making sure that we understand how the patient [has] been doing between visits, making sure that they haven't had those emergency room visits.

As far as how we're tracking how they're doing and how quickly they're improving, it really depends on the agent that we're using and how quickly we expect them to improve.

Editor’s note: Disclosures for Gupta include GlaxoSmithKline, Genzyme Corporation, Novartis Pharmaceuticals, Genentech USA, AstraZeneca Pharmaceuticals, Dermavant Sciences, and more.

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Payel Gupta, MD, discusses how IgE, FeNO, and type 2 comorbidities inform biologic choice and when a lack of response warrants switching agents.

Payel Gupta, MD

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