Severe and Uncontrolled Asthma: Tailoring Therapies for Complex Patients (Recording)

This webinar was recorded on March 18, 2026

Despite advances in treatment, many patients with asthma remain uncontrolled, experiencing frequent exacerbations, persistent symptoms, and reduced quality of life. Managing severe and uncontrolled asthma requires a personalized, evidence-based approach that accounts for disease heterogeneity, comorbidities, and patient-specific factors.

Join us for this CME-certified webinar as Dr. Leonard Bacharier reviews current best practices for evaluating and managing patients with severe and uncontrolled asthma. The discussion will cover severe asthma as a difficult-to-treat disease and will review phenotyping and biomarker data to select appropriate advanced therapies, including biologics.

Speaker:
Leonard Bacharier, MD

Dr. Bacharier is the Janie Robinson and John Moore Lee Chair in Pediatrics, Professor in Pediatrics at Vanderbilt University Medical Center, Section Chief of Pediatric Allergy and Immunology, Scientific Director of the Center for Clinical and Translational Research, and Director of the Center for Pediatric Asthma Research.

He is a pediatric allergist and immunologist with extensive experience in asthma research, particularly clinical trials.  He has led and participated in multiple federally funded, multicenter clinical trials in childhood asthma.  He has published over 300 peer-reviewed manuscripts based on these projects.  Dr. Bacharier is the only American pediatrician on the Global Initiative for Asthma Science Committee. He is also the Secretary/Treasurer of the AAAAI and an Associate Editor for The Journal of Allergy and Clinical Immunology. Additionally, he is the Editor of the two leading textbooks in the field of allergy and immunology.

This Advances webinar is in partnership with the American College of Allergy, Asthma & Immunology. ACAAI offers CMEs for physicians for this webinar. If you are a member of ACAAI, you can obtain CME through the member portal for the Advances webinars.

All attendees will be offered a certificate of attendance. No other continuing education credit is provided.

CME is available through ACAAI for this webinar.

Sponsored by the American College of Allergy, Asthma and Immunology

Transcript: While this transcript is believed to be accurate, errors sometimes occur. It remains your responsibility to evaluate the accuracy and completeness of the information in this transcript. This transcript is not intended to substitute for professional medical advice.

Tonya: We will give it one more minute to let everyone get into the webinar. Hello, everyone. Thank you for joining us today. My name is Tonya Nash, CDC Excel product manager at the allergy and asthma network. I’m delighted to welcome you to this afternoon’s CME accredited webinar. We have a special presentation to you today focused on tailoring therapies to meet the needs of severe asthmatic patients. Before we start today’s program, I would like to cover a few housekeeping details. First, everyone will remain muted during the webinar to minimize distractions. We will record them at session and uploaded to our website in about one week. You can watch all of our recorded webinars at allergy asthmanetwork.org. Our webinar is scheduled to last one hour. There will be a Q&A session after the presentation. You can send your questions to us using the Q&A box at the bottom of your screen. A team member will check the chat for any questions or help you need. We will do our best to answer as many questions as possible before we finish. This advances webinar is brought to you in collaboration with the American College of allergy, asthma, and immunology. The college offers continuing medical education credits for physicians and attendance credits for others. You can create a free account to earn CME or attendance credits, or advances webinars being — via the member portal. All attendees will receive a certificate of attendance. Please note that no additional continuing education credits will be provided. A few days after the webinar, you will receive an email containing supplemental resources and a link to download your certificate of attendance. We will share the link to the certificate of attendance in the chat toward the end of the webinar. Next slide. Today’s presentation is titled ” severe and uncontrolled asthma: Tailoring therapies for complex patients.” While many individuals with asthma may achieve good control, some continue to struggle with persistent symptoms and frequent exacerbations despite appropriate treatment. Complex cases require us to look deeper, considering feeding — phenotype, biomarkers, comorbidities and individualized treatment strategies. With that, it’s my pleasure to introduce today speaker, Dr. Leonard Bacharier. Dr. Bacharier holds the Janie Robinson and John Morley chair in pediatrics, and as a professor of pediatrics at Vanderbilt University Medical Center. He serves as the section chief of pediatric allergy and immunology, scientific director of the Center for clinical and translational research, and director of the Center for pediatric asthma research. As a pediatric allergist and immunologist, he has extensive experience in pediatric asthma research, especially in clinical trials. He has led and participated in numerous federally funded, multi-center, clinical trials in childhood asthma, resulting in over 300 peer-reviewed manuscripts from these projects. Dr. Bacharier is the only American pediatrician on the global initiative for asthma science committee. He is also the secretary treasurer of the quad AI and associate editor for the Journal of allergy and clinical immunology, and editor of the two leading textbooks in the field of allergy and immunology. Thank you for being here, Dr. Bacharier. I will turn it over to you.

Dr. Bacharier: Thanks, Tanya. Good afternoon, everybody. Appreciate the allergy and asthma network inviting me to participate in this very well-received webinar series into everyone for taking some time out of the middle of what I’m sure is a very busy early spring day, to talk a little bit about how we are approaching our patients with the most challenging degrees of asthma. Here are my disclosures, relevant to today’s discussion. I’m going to spend a fair amount of time talking about Biologics, and I have had interactions with all of the manufacturers of these products. We have three objectives for today’s discussion. First is to define and differentiate what we mean by severe and uncontrolled pediatric asthma. Then talk a bit about how to evaluate and interpret take two biomarkers in an effort to better phenotype our patients. And then lead to biomarker and phenotype driven care. Finally, to apply the evidence that we now have from pediatric trials that allow us to individualize and personalize the care that we provide these patients. In order to talk about the management of severe asthma, we first have to come to agreement as to what we mean by severe asthma. And that is a much more challenging effort than might be expected. Because we really don’t have a consensus definition as to what severe asthma is. 

Two leading sources in this area, the global initiative for asthma, and the guidelines put forth by the ERS and ATS, have attempted to do this for us. And it is really based on the amount of therapy required for a given patient. This generally means step four or five level therapy, often with secondary controllers, that are either effective in achieving disease control, but disease control lapses when these medications are reduced or withdrawn. Or despite use of this high intensity therapy, asthma remains uncontrolled. Furthermore, the ATS ERS guidelines suggest if you require systemic steroids for at least half of the year, and your asthma in order to maintain or inadequate to maintain control, that your asthma would be severe, I personally think 50% is way higher than what would define severe asthma and the current age and certainly patients who require frequent oral steroid bursts might very melt — very well meet this definition. As we have learned over time, there is no one form of asthma. There are a variety of subforms of asthma. We call these asthma phenotypes, we call these patterns of asthma. This has become important as we have now developed therapies that only work in specific set types of asthma. In order to really add or stand these, it is worth taking half a step back and looking at what we mean by these asthma phenotypes. One good example of this is what was done in the NIAID’s APIC study, which was a study of kids who lived in American inner studies who had asthma but could enter regardless of asthma severity. It was a 12 month perspective trial, or study. Every child receives a standardize guideline-based care for both asthma and rhinitis with medications provided to the patient’s. They were evaluated every two months and treatments were adjusted based on levels of disease control using a standardized approach. They defined asthma in three different ways. Based on the amount of therapy required for the disease. 

Children were considered to be easy can to — easy to control if they require 50 micrograms of flu took a scone, no controller they were considered difficult to control if they required at least 250 micrograms twice a day with or without a LABA. They were indeterminate if they were anywhere between these two. The real contrast was between early easy to control and difficult to control. Then using clustering analysis, we asked the computer to put children of like patterns together. And what we found is in this group of unselected children with asthma, it could actually be categorized into five different patterns of disease, and I really want to focus our attention on a few of these. What you will see here is a heat map, the lighter the blue means the lower the value for a given future. The darker the blue, the higher that value. And what you see is indicators or markers of asthma severity, lung physiology, rhinitis severity, allergen sensitive is Asian and markers of inflammation based on blood use and accounted for no levels. The first thing we see is there are two groups who have an awful lot of what we call take to high inflammation. — call type two high inflammation. What you see is that just because you have a high blood he is info count or a high pheno does not mean you have comparable degrees of asthma severity. The children in group e have the most severe asthma, they had the highest score as it related to use, exacerbation frequency, extent of controller needed. They have the lowest degree of lung function. They had since — they had substantial dilator response. They had high levels of rhinitis. They were sensitized to a large number of allergens. They had a high IAG level. 

There is another group of children who had very similar degrees of type two inflammation. Very similar extent of allergic sensitization. Their answer is actually pretty mild. They did not need nearly as much of utero. There exacerbation frequency was less than half of what it was for group e. They had better though not entirely normal function. Even in those who have take two high asthma, they are not all the same. One third of them had the most severe form but two thirds of these type two highs had less severe asthma despite having markers of type two inflammation. Contrast this to group B. This group had the least amount of type two inflammation. They had low levels of pheno, low levels of — they were sensitized to 14. Look at their asthma severity indicators. They look a lot more like group e children then group d children. These children have substantial amounts of asthma without a type two signature. We call these children type two low. Then there were a couple other groups, one group that had very mild disease in all forms. And one that had a modest amount, but still very mild asthma. We look to our national and international guidelines to help guide our thought process on how to manage patients with moderate to severe asthma, who are more difficult to control. This is the approach that is in the 2025 document. I will alert you that on world asthma date in early May, Gino 2026 –GINA 2026 will be released. I encourage you to watch out for that. What we see is the management of asthma is this arrowed circle of SS, adjust, and review. This gets overlooked a lot when we look at a slide like this. 

People jump right away to what medicine should I use? In order to get the medication right, we have to assess the patient correctly. We have to see them regularly and adjust in the review is essential because this is not a static disease, it’s dynamic. What was adequate at one point in time may not be adequate at any further point in time. Our discussion today will focus on children, who despite medium dose ICS LABA or maintenance reliever for therapy, remain uncontrolled. The Gino said — the GINA digestion be that they be referred to assessment, consider a trial of higher dose in steroid therapy. That is generally infected — ineffective in children who are already receiving a medium dose. And consider add-on therapy, only as a last resort. In 2026, they should be an exceptionally where event. When we talk about asthma phenotype and what that really reflects, or what it really requires, it is about assessing phenotype when patients are on high intensity therapy, or their lowest possible dose of oral steroids. The markers that have borne out as indicators of underlying type two inflammation, type two high asthma, include any of the following. Lettie’s ceiling fills, a Fino of 20 parts per billion, if asthma is clinically allergen driven, or for patients who require maintenance. 

These factors may not be detectable because oral steroids are very effective in driving down all of these measures. It is also important to remember that these factors are also dynamic over time. And that a single measure may not capture a patient’s underlying type to information adequately, and we recommend this may be repeated up to three times on the lowest possible oral steroid dose, and as far removed from a course of oral steroids. With studies showing oral steroids can affect counts for weeks to months in some patients. Keeping that in mind is essential in determining whether a patient has underlying type two inflammation. Now let’s turn our attention to the management side of things with our biologic agents. What we have here is the typical confusing Graham of a variety of cell types essential in the inflammatory pathways that characterize many patients with childhood asthma. It’s a Horton to note — it’s important to note that all of the Biologics we are going to talk about today are intended for children who have type two high asthma. There is only one approved for children over 12 that has ever demonstrated efficacy in patients who don’t have evidence of type two inflammation. We will talk about that briefly. 

This collection of agents is focused and targeted to patients who have evidence of type two inflammation. We will talk about each of these as we go. At present come in children six and above, and I’m really focused on the six to 11 age group, the FDA has approved four Biologics for children with type two high asthma. The first, and the one that was approved earliest, was close to monoclonal antibody. It binds free IG circulation, thereby preventing it from binding to its receptor on the surface. It has no biologic activity and thus, this reduces the effects of allergen on driving an inflammatory response. A monoclonal antibody against IL5 , produced by type two cells but is essential for the groped of — growth develop and and survival of eosinophils. By binding IL5, it prevents it from interacting with its receptor. This effectively starves the eosinophil. It removes its essential growth factor, and leads to market reduction in eosinophil numbers. After administration. The third agent is an anti- ILSR, it binds to the receptor on the surfaces of eosinophil. After binding, it attracts other immune components that lead to the death of these eosinophilS. It results in the rapid depletion of whole body eosinophils, and its downstream effects. Finally, there is dupilumab. This Alpha chain is a shared component of receptors for the cytokine’s IL4 and IL13. Intel’s B cells to produce IGE, the antibody is central for allergic inflammation, and as a shared component of the receptor for IL-13 which is important for mucus production and other components of airway inflammation. 

In this monoclonal antibody blocks those downstream effects. We talk about the clinical outcomes related to these therapies as we go. So, we are now very fortunate that we have a robust data set of use of these agents in clinical trials in children, that really do help guide our understanding as to who do they work for, how well do they work, and what should our patients expect. I’m going to spend a bit of time talking about two of the larger trials that we have had the opportunity to be part of. Because I think they are really informative in teaching us where these agents fit in and what to expect from them. We will start with OMALIZUMAB. This has been around the longest I highlight data from the inner-city asthma Consortium that showed the addition of the standard asthma care use the risk of exacerbation from 50% in the placebo group to 30% in the omalizumab treated group. And that it nearly in them and aided the seasonal peaks of exacerbation that we all are well aware of in the fall and spring. Omalizumab is effective in reducing the risk of exacerbation in children with severe allergic asthma. If there is no evidence of allergic sensitive visitation, omalizumab is not to be effective in that subgroup. The anti-IL-5 antibody was originally approved in patients 12 and above and subsequently extended to children age six to 11 in an open label study that supported comparable pharmacokinetics. But we still didn’t have a real good sense as to how effective this therapy was going to be in children with eosinophil asthma. We conducted the Muppets two study. This is a double-blind randomized placebo-controlled trial of children six to 17 years of age living in urban centers in the U.S. who have difficult to control asthma, have had at least two exacerbations in the past year, and who have evidence of eosinophil asthma. Children were maintained for four weeks on their standard of care, and randomized to have either mepolizumab was a bow a month injected so butane is Lee on top of guideline-based action and — asthma management for one year with the primary outcome being the number of asthma exacerbations between the two to. Give you a sense of what this study population looked like, we randomized 290 children. What you can see is one third of them had a BMI in excess of 95th percentile. 

There was evidence of type two inflammation, and that there FeNo’s were about 400 per million per their total was around 400, and they were sensitized to multiple allergens, seven or eight allergens per child. 97 to 93% had a positive test — skin test with one inhalant to allergen. Not unexpectedly, despite them having very severe asthma with type two markers, their lung function was well preserved. 92% to 94% predicted for baseline FEV1. Significant airway reversibility. Two thirds of them were receiving high-dose ICS therapy and they averaged almost three oral steroid bursts per year. These children clearly have severe eosinophil type two asthma. Although they do have quite well preserved and Vivi one — FEV1’s . After administration of mepolizumab, we saw a rapid reduction, from a baseline of about 400 to around 100 this was maintained over the duration of the study in the placebo group. It did not change over the duration of the study. We looked at nasal washes and also Sinovac it resulted in a significant reduction in upper airways, in a manner greater than what was seen in placebo. Eosinophil clearly rues — clearly reduced the burden in these children. Here is the primary outcome, the rate of asthma exacerbations requiring oral steroid or hospitalization. 

Placebo group in red. What you see is the rate of exacerbation was higher in the placebo group and lower in the mepolizumab group. This resulted in a 27% reduction in the rate of exacerbation, a statistically significant and clinically meaningful effect. We were surprised because in the studies of mepolizumab in adults, the rate of exacerbation reduction was closer to 50%. We saw a reduction of about half of what we were expecting and we really needed to better understand why it was that these children did not respond as well as we had expected. Maybe it was chance, maybe it was there inner-city environment, maybe it’s something else. But this was a less robust effect than we had anticipated. We looked at secondary measures to see if it gave us other insight as to what effect mepolizumab may have had. We looked at the composite asthma severity Index, a score that integrates symptoms, overall use, control or Medicaid step, and we saw it went down, got better, in both groups ended so very similarly with no difference between mepolizumab treatment children and placebo. We looked at FEV1 per addictions and son no difference at all over the duration of the study between mepolizumab treated children and placebo for FEV1. 

Norton we see differences for the FEV1 or F EV C ratio. No lung function impact of this therapy. We saw a reduction in exacerbations, but no meaningful impact on secondary outcomes. But indeed, effective in reducing exacerbations in children. The monoclonal antibody against the IL-4 receptor, was FDA approved based on data in results in this study in children. Showing comparable blood levels of the monoclonal antibody in children as were seen in adults. There was no placebo group here. So we really to date don’t have a sense as to the magnitude of clinical effect that will be seen with this in children. In practice, there is an ongoing clinical trial that will attempt to answer that question. At the moment, we cannot provide an estimate for exacerbation reduction with benralizumab in children. The monoclonal antibody against the IL-4 receptor chain, we study this in two sequential studies, voyage and double-blind, placebo-controlled randomized trial of dupliumab in a weight of pendant fashion every two weeks for one year. At the end of that trial, children were offered the opportunity to enroll in the excursion study, which was an open label extension for an additional year. The vast purity did so. We will talk about both of these results. 

For voyage, we enrolled children six to 11 years old with moderate to severe asthma. They had to be unmediated — medium dose. They had to have an FEV1 no higher than 95% predicted, with a reversibility of 10%. They needed at least one severe exacerbation in the prior year and they had to have uncontrolled asthma. The primary study population of interest were children who had a type two inflame your — inflammatory phenotype, children who had a count of 150 or a Fino of at least 20 parts per billion. We rolled children irrespective of these but the primary analysis was done in children who had a type two phenotype. We also look at those who had a count on the higher side of 300 cells per microliter. These children are very similar to the ones we saw in the Muppets two study with a couple exceptions. The national study enrolled nearly all white children. There were very few children other than Caucasians in the study. Unlike what we saw in the Muppets two trial, the lung function amongst this population was more compromised, with an FEV1 in the high 70% range. Comparable levels of bronchodilator reversibility, poor asthma control as assessed by the asthma control questionnaire, significant degrees of type two inflammation. 

Their IGE’s were Ford to 500, Fino’s were about 40 parts per billion in more than half had a Fino of 20 parts per billion. Another group of children with type two high uncontrolled asthma. Here, we saw there was a significant reduction in the rate of asthma exacerbations, similar type of outcome of what we saw in the trial. The magnitude effect was significantly greater in the children who had the type two phenotype . We saw 59% reduction in that rate of exacerbation. In those who had a count of 300, we saw 65% reduction in the rate of exacerbation. Even using a count of 150 showed a 61% reduction, and in the population as a whole, irrespective of baseline biomarkers, with a 54% reduction in the risk of exacerbation. Significant reductions in exacerbation rates favoring dupo lumab. No effect over placebo in this trial, there was. For both the type two phenotype and those with 150. These children improved five FEV1 percentage points over placebo in both of those groups. Children who have the highest pheno levels, 20 parts per billion, irrespective of their account, actually had an improvement of 6.74 percentage points over placebo. If we look at lung function over time, focusing on the left, these are children with a type two phenotype. In gray is the FEV1. In the placebo group, it does improve after two weeks and it is maintained over the duration of the 52 trial whereas the children who received dupilumab have a greater improvement by two weeks after the first dose, that continues to improve to week 12 at the five percentage point advantage. This is maintained through the duration of the study. 

Very similar pattern in children who had a count of at least 300. We look at asthma control based on the asthma control questionnaire scores, we also see differences in favor of dupilumab treated children with improved AC Q scores in the type two phenotype and in those with accounts of excess of 300. As I mentioned, after the double-blind study, all children were offered the opportunity to participate in excursion. Those who were on dupilumab for continued on dupilumab, and those who were on placebo during voyage were started on open label. Dupilumab, this was given in a weight-based fashion. They were followed for an additional year. What we saw is that the rate of exacerbation continued to go down in children, regardless of whether they received dupilumab during voyage. In blue or whether they received placebo during voyage and were switched to dupilumab. Excursion was done during the early part of the COVID pandemic, so there was a bit of a COVID affect in the reduction of exacerbations. When we look at children who were in excursion pre-COVID rather than during COVID, we realized the COVID affect was pretty minimal on the reduction of exacerbations. The lower panel, we see the effect of dupilumab therapy on lung function. Here is the dupilumab treated children for the first year in voyage and continuing on dupilumab. We see a continued advantage in terms of FEV1 percent predict. I want to point out that in the placebo group, as soon as they started dupilumab, there lung function goes up it is very encouraging. It never quite gets as high as the children who started on dupilumab a year earlier. 

This makes us wonder if this additional year of under type two inflammation and ongoing exacerbation, leads to airway damage, that was then no longer recoverable with the addition of dupilumab. An anti-TSL Mina global antibody. It is only approved for 12 and above. We don’t have a lot of data on its efficacy in children above the age of 12 years. But what has been seen is that there is a reduction in exacerbations on an improvement in lung function in patients receiving tezepelumab over placebo. One of the real challenges in trials of Biologics is a very pronounced effect of diversity. As I mentioned earlier, the voyage trial was done largely in Caucasian individuals whereas the Muppets two trial was done in children in inner-city America, where the vast majority were black or of African-American race. And it really speaks to the importance of trials to target these populations. These have been done in other spaces and really do require close attention and an intentional effort to enroll the most diverse population is as possible, so the results are most generalized. To summarize the efficacy of Biologics in children with severe asthma, we see that of our four major Biologics, here are their effects on lung function. They range from 27% to 59%. These are not head-to-head comparisons, is not to say that had they been compared head-to-head, this is what we would have seen. But there is a variation and variability in the extent of exacerbation reduction and the trials we have. When we look at lung function effects, we see the anti-IGE did not demonstrate meaningful effects in that. The dupilumab did demonstrate a five percentage point increase. We need more trials in children. Fortunately, we have some, I have reviewed the longest ones with you today. Muppets two in the voyage study. 

But there is inadequate amounts of data, particularly in adolescence for almost all of these Biologics. Real effort needs to be paid to better study and better include these children in future efforts. How do we know which children are going to respond? We use biomarkers. What we have seen is these biomarkers are quite good at identifying children who are going to have benefit from these Biologics. Here is some data from the trial showing even though this drug targets IGE, your eosinophil and FeNO are predictors of exacerbation benefit. At least 2% or eight FeNO of 20 parts per billion is associated with twice the likelihood of an exit obey — exacerbation benefit. In a similar pattern that was seen in patients, adult patients, in terms of eosinophil s counts as a predictor of response to anti-IGE. It is not just the target of the response. It is the underlying extent of type two inflammation that really does seem to matter. When we look at mepolizumab in adults, there is a clear relationship that as you’re letting eosinophil goes up, your magnitude of reduction of exacerbations goes up as well. Unfortunately, in children in the MUPPITS2 trial, we did not demonstrate that effect. There did not seem to be a clear relationship between bloodied eosinophil count and extent of reduction. If you were 150, you are not all that different than if you were 200 or 350. For dupilumab we saw both, FeNO and blood eosinophil were able to predict the amounts of dupilumab therapy with higher levels of each of these being associated with greater response. But in the converse, it was not true. If children had no evidence of type two inflammation, i.e. blood eosinophil under 150, and FeNO less than 20, there was a very low likelihood of an improvement. And here we see no effect on either exacerbations or lung function in children who had low levels of both biomarkers. In contrast, as the biomarkers go up over 150, the magnitude of effect on reduction of exacerbations or improvements in lung function exist such that it is children with higher blood eosinophil count or higher FeNO to get greater benefit than those who have lower levels. Here is a flowchart, there are many of these available, that talk about how to choose between Biologics for a given patient. 

They start with identifying your patient is difficult to control, trying all of the other non-Biologics step ups after you have confirmed the diagnosis, inhaler technique, and comorbidities. Once you have severe uncontrolled asthma, you then phenotype your patient based on their blood eosinophil count, they allergic status and lung function. Then we subdivide them based on those factors. Blood eosinophil under 150, led eosinophil 152 1500 and blood eosinophil in excess of 1500. We sub categorized them based on whether there FeNOs are below or above 20 parts per billion. Then we sub categorized based on whether the asthma is considered allergic or nonallergic. Then we think about which of the agents based on these categories are shown to be effective in those spaces. You can see shows. I also want to remind you these are agents that have other effects and other type two disorders. Such that there are patients who will have coexisting conditions. Some of these Biologics work and multiple conditions such that if you have a patient who has say, a topic — atopic dermatitis, asthma, you might choose a biologic like dupilumab which is effective for both of those. Or you have a patient with food allergy and allergic asthma, you might think about omalizumab as a preferred treatment option because you are able to target two diseases with a single intervention. Here is another table that really says same thing, but just divides the patient’s based on whether it is allergic or nonallergic. And you see the options here are all presented in alphabetical order, because we don’t have head-to-head comparisons to say one is definitively better than the other. Here is a general table that summarizes these agents, who they are approved for, what they are effective in. They are all given sub butane is, all approved for home administration. 

Dosing frequency varies based on the age, the weight, and the total IGE level. You can see that they vary based on their eosinophil thresholds. Biologic therapy in children really is a great place to use shared decision-making approaches, where you are able to better identify patients believes — beliefs, goals, and preferences. Patient’s goals may not totally aligned with our goals. Every family has a different viewpoint. I think it is a central we present all options favorably and fairly. We’d be candid about injections and offer strategies to reduce anxiety and discomfort. I will tell you there are a lot of families that are slow to start, but I have not yet had a family that stopped because of the injections. So I don’t think this is as big of a barrier as we might think it would be, because these are children whose asthma is difficult to manage, and these are very frustrated families who are willing to do more to help their children lead healthier lives. A few practical aspects around Biologics. This is very much unlike immunotherapy, these are all fixed doses, no adjustment needed for missed or late doses. There is home administration approved for all of them, but some of them have differences. Some, as auto injectors, come as standard syringes, some commas either. Autoinjector based on the black box remains required for patients receiving omalizumab therapy. 

It is essential to follow administrative guidelines to minimize injection site reactions, in particular, dupilumab, which is not allowed to come to room temperature, really does stain. We encourage them to let this come to room temperature before administering it. Even though we use biomarkers to start, initiate, interest therapy, they really aren’t helpful in monitoring therapy. Unless there is a suspicion of side effects or other issues, we generally don’t recommend routine monitoring of blood eosinophil . How do we assess if it’s working? We see our patients back regularly. A lot of patients stopped coming back because these medicines work so well, they don’t think they need us anymore, but they do. I recommend we see them every two to three months, and we assess response at four to six months. These drugs take a little bit of time to work so I would not make any decisions about responsiveness early on. What we saw is that the best of these agents reduce exacerbation rate by 50% to 60%. That means there will be patients who continue to exacerbate on these agents, and therefore, an exacerbation does not reflect an inadequate response. Multiple exacerbations probably do. But a single exacerbation is absolutely not inconsistent with a response. What are we looking for? Dear with him for exacerbation reduction, symptom improvement, reduction in rescue med use. We want to reduce, ideally eliminate oral steroids, we want quality of life to be better. And we want lung function to be better. Not everybody gets all of these but many to most patients get a reasonable number of these. If they are doing well, continue. If they are doing so so, continue for up to 12 months. If there is clearly no efficacy, and occasionally we see that, we recommend switching to an alternative agent of a different mechanism of action. In the vast majority of patients, you will find a biologic like it’s the job done for them, but it may not always be the first one you choose, even if you use those algorithms religiously. 

Occasionally the patient’s disease behaves differently than you would have expected. When we have seen today as there are many phenotypes of asthma, and their biologic pathway that drives the, we understand some but don’t understand all. We have a handful of Biologics approved for asthma in children and adolescents. They really all target type two inflammation. They all lead to reduction in exacerbations. Their effects on lung function and biomarkers are a little less consistent. We continue to have no head-to-head comparisons of these agents. I don’t think we are going to have very many of these at any point in the future. There are indirect treatment comparisons and network analyses that have been done. The results are generally inconsistent as well and are really focused on data in adults. They really don’t help guide our thinking in children. We really do need more research in the space. We need studies that further help us understand how to choose between the agents, because many of these patients have what we call overlapping phenotypes. If you have a count of 300, there are at least three agents we can choose for any of those patients. How do we know which one is the right one for that given patient? We really don’t. We are learning that we still have a long ways to go. I want to remind you that the global initiative for asthma has a lot of really wonderful resources, including the strategy report, summary guide, severe asthma guide, here is a QR code to help get you there. There are slide sets, podcasts. Like a said, in May, we will have an updated version in 2026, taking into account all of the developments that have occurred in the last year. With that, I want to thank asthma and analogy network to allow me to talk with you today and glad to open it up for some questions. Thank you.

Tonya: Thank you, Dr. Bacharier for the excellent presentation. The information you shared with us today provides great resources for severe asthma management. We have several questions and we will try to get to as many as we can before the end of the webinar. Let’s start with this first question we received early on in the presentation. At what stage of asthma should we use Biologics, and how optimistic should we be about the results?

Dr. Bacharier: So, that is a really important question. All of our studies to date have been in patients who have pretty substantial and advanced asthma. It’s actually remarkable to me how well these agents work in those patients. I suspect they work very well in patients with less severe disease. But, given the cost considerations in the administration considerations, they are generally reserved for patients with more severe disease. We don’t understand yet if these agents alter the disease at all. In other words, if the patient were to start on these therapies earlier, with their asthma be less severe for a lifetime? With a B able to come off of these agents? Would there asthma lesson in severity? Don’t know the answer to any of these questions. Clinical experience tells us any patients do very well, and we have been able to stop Biologics in many patients, because of their excellent disease — lack of disease progression. We don’t know if that is because of the biological changed their disease, or their biologic kept their disease quiet while it was getting better on its own. Because a lot of children with asthma do just that. I think we have an awful lot to learn about when, where, and for how long we should be using these agents. I think the findings from the voyage and excursion study remind us that delaying these therapies can have consequences, in that those children who started on dupilumab a year later because of the clinical trial did not gain back as much lung function as the children who started it a year earlier. We don’t know if that is — if that applies to all of them, if it was a unique population, but it does beg the question, does timing within the disease matter? And I think the answer is it probably does.

Tonya: All right. Actually, you kind of responded to some of the questions that are next person had asked, which is, do you see a time when Biologics would be first in line therapy for children with moderate to severe asthma? It seems that lung preservation is likely key here, even with treatment with ICS. Do you have any information on the winning Biologics?

Dr. Bacharier: I think we touched on most of that. I think time will tell. The cost of administration issues are going to keep these agents at the higher levels of severity for the foreseeable future. That may not be the best biologically driven answer, but I think that is the reality of it. Weaning has been unstudied in children. It has been studied pretty well and it doesn’t work. When you remove these agents and adults with type two asthma, they get worse. In children, many of us are hopeful that keeping the disease quiet for a time might be followed by a time where you might be able to do this. I think this is completely off label, but it requires — this is the art of medicine. Patients doing super well, no exacerbations for years, normal lung function, can’t recall the last time they needed a bronchodilator, certainly has not needed a course of oral steroids. You can think about strategies in reducing their background on biologic medicines, but then potentially spacing out the frequency with which you administer the biologic versus stopping it. We don’t have a clinical trial driven approach for that. This is sort of a good discussion to have with your patients and come up with a strategy, and see if it works. If it doesn’t work, you just go back to where you were. Which was working. These are medicines. They have an on effect and off effect.

Tonya: Question, to what extent do you find asthma diaries useful, when managed by parents or older children versus being used primarily by primary care providers to inform that a specialty referral might be appropriate? If you considered it valuable, what key data points with allow the most insight into the optimal treatment plan?

Dr. Bacharier: I think they have value in the right hands. I will tell you, that most families have limited motivation to diary their children’s asthma sentimentality. I like them, where folks can’t really estimate how often they are symptomatically. How often they are using something. Or what they are telling me seems inconsistent with what I’m seeing. I think albuterol use, nighttime awakenings are probably the two most important diary elements, if you are going to use them. There are electronic versions now, but I think the key is having some tool to get added. The other way to get at these things now is to use one of these questionnaires, the asthma control test, the childhood asthma control test. These are validated against diaries. We know there are scores of people who report on them and are consistent with what people would say in a perspective diary. Using them to gain quantitative assessment of asthma control is often pretty helpful. I think that really does help get around the burden of asking people to keep a diary, which in my experience, has been pretty unhelpful for the most part.

Tonya: OK. Well, thank you Dr. Bacharier, for such an insightful and engaging presentation. Thank you to all of you for joining us. We hope this session has provided valuable tools and strategies to support your practice in the management and treatment of complex asthmatic patients. In a few days, Zoom will emailing you a link to this recording, supplemental resources, and a post webinar evaluation. Your feedback is very important to us and it helped shape future programs. Going as next month for another advances webinar on April 16, 2026, at 4:00 p.m. Eastern standard Time, as Dr. Clint Dunn presents chronic Arctic carrion, and — antihistamines, Biologics, and be Kiké inhibitors. On behalf of the allergy and asthma network, thank you again for your presentation. We look forward to seeing you at our upcoming webinars. Have a wonderful rest of your day.