<p>Biologic therapies have reshaped care for type 2 inflammation in asthma, in part by reducing dosing frequency and lowering the day-to-day burden that often impacts adherence. This article highlights emerging evidence on the influence that biologics may have on airway remodeling and mucus production, also providing information on practical clinical considerations that can help clinicians choose among the available options.</p>

Biologics have really been a big innovation for people with type 2 inflammation–high asthma, which is characterized by high levels of inflammatory mediators. This innovation is important because biologics are administered less frequently than inhaled asthma treatments, and people are often nonadherent to inhaled asthma treatments. In some cases, you are asking a patient to take a medicine several times per day, every day, whether they are feeling well or not. When a patient stops taking an inhaled therapy, it may take, for example, several weeks to see the inflammation return, and they will often resume the medicine when they become symptomatic, expecting it to work immediately. These treatments are not intended to work that way. They are meant to be proactive, not reactive.

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The biologics that we have right now for asthma vary in their dosing frequencies, with the most frequent being every 2 weeks, and there are also biologics with dosing frequencies of monthly and every 2 months. Further, we now have a medicine (ie, depemokimab) that is dosed twice yearly. This variety of dosing schedules for biologic therapy opens up a whole new world to us with regard to improving adherence and, hopefully, achieving prolonged asthma control.

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Several studies have shown that airway scarring or remodeling may occur in patients with asthma. Asthma-associated inflammation within the lungs can essentially induce scarring and mucus production. There have been 2 related studies that are really interesting: VESTIGE and MESILICO. The VESTIGE trial demonstrated that dupilumab diminishes mucus production. In this study, sensitive computed tomography scans showed that people taking dupilumab were able to breathe better and have air reach more distal parts of their lung. The multicenter MESILICO study from Greece showed that people with long-standing asthma have airway remodeling. When investigators put these patients on the anti-inflammatory biologic mepolizumab for 1 year, indices of airway tissue remodeling were reversed, which is really remarkable.

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I think that, in many cases, clinicians may feel overwhelmed by the process of selecting the most appropriate biologic for a patient’s asthma. The data are really fragmented. However, there are some indicators or surrogates of likely efficacy. In the case of mepolizumab, it is the eosinophil count being elevated, which is similar for benralizumab. In the case of omalizumab, an indicator of response is a perennial allergen with elevated IgE. For tezepelumab and dupilumab, an elevated fractional exhaled nitric oxide level may be an indicator of response, but the data are not as well worked out as we would like.

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The study by Kavanagh and colleagues is one of the most interesting ones to demonstrate this. Investigators looked at people who were on mepolizumab and tried to identify the super responders vs the nonresponders. They found that requiring a lower oral steroid dose, having concomitant nasal polyposis, and having a lower body mass index at baseline were associated with better outcomes. Additionally, super responders had an elevated eosinophil count; the higher the eosinophil count, the more likely they may be to respond. So, who is likely not to respond? These are patients who require high doses of oral steroids or have concomitant illnesses such as gastroesophageal reflux disease.

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Asthma has become a biologic world, and we are going to have to begin to hone our skills through the continued evaluation of the data that are available and through further studies to better define responders and identify those patients who are most likely to respond to a given therapy.