Wendy Moore, MD, on Biologic Medication Use, Switching Therapies for Severe Asthma
Biologic therapies are an increasingly important treatment option for patients with severe asthma following the addition of newly approved biologics, according to the results of a recent study presented at CHEST 2020.1
The researchers are conducting the CHRONICLE Study, which is an ongoing “real-world” observational study that examines the use of omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab in patients who are followed by subspecialists for their severe asthma. The frequency of use for each of these medications was recorded. The researchers also observed how frequently patients switched from one medication to another and the reasons behind those switches.
Study author Wendy Moore, MD, who is a professor of medicine and director of Clinical Pulmonary Research at Wake Forest School of Medicine in Winston-Salem, North Carolina, answered our questions about the study findings.
Pulmonology Consultant: Your team found that biologics were frequently used by subspecialists to treat severe asthma. Is this a result that surprised you, or did you anticipate this?
Wendy Moore: No, that did not surprise me. The arrival of biologics on the market for severe asthma opened up a huge therapeutic space that previously only contained inhalers and oral steroids. This group of patients was out of options for many years; they had asthma symptoms that limited their lives, some of them could not work due to absenteeism, frequent exacerbations that required oral steroids (and all the adverse effects that prednisone can give you—obesity, diabetes, osteoporosis), trips to the emergency room and hospitalization, not to mention the expense of their current therapy (3 or more inhalers, nebulizers) that was not improving their symptoms. Subspecialists and their patients with severe asthma had been waiting for a new therapy for many years. The bigger issue is that not all severe asthma patients are candidates for these therapies, so they still do not have any options other than standard asthma care.
PULM CON: How do you believe these results about biologic medication use will impact the current treatment landscape for severe asthma?
WM: As stated above, the biologics changed the entire landscape of severe asthma treatment, but only for a subgroup of patients. These patients are “T2 high” patients—they have elevated T2 biomarkers, elevated blood eosinophils and/or allergic sensitivity/increased immunoglobulin E (IgE) and/or high measurements of exhaled nitric oxide. They qualify for the current FDA-approved biologics that target IgE (omalizumab), eosinophils (mepolizumab, reslizumab, benralizumab) or lymphocytes (dupilumab). The “landscape” for the subgroup of patients with no T2 high biomarkers is unchanged unfortunately—no new options. There is a great unmet need for new therapeutics for the T2-low group.
PULM CON: It was noted that approximately 10% of patients switched from one biologic therapy to another. What is the clinical importance of this finding?
WM: Biologic switching is a symptom of the imprecision of the big picture question of which biologic is the best biologic for a given patient. Most clinicians pick a biologic for a patient based on their biomarker profile and clinical features. If it is the perfect match, home run! They have a super response and feel like they no longer have asthma.
What is much more common is a “partial response” when patients are better but not a home run or “no response,” meaning they still require a lot of oral steroids and have exacerbations. This leads to the thought that perhaps a different biologic would work better, so you switch and see what happens. I was surprised it was only 10%. I thought it would be higher because those “home run” patients are not all that frequent. So, patients/clinicians are settling for “better overall” and sticking with the biologic they chose originally. This may be the right answer because it may be that the reason there is only a partial response is that there is coexisting T2-low inflammation that is not treated by any of the approved biologics, so switching will not make a difference at all. Do clinicians not switch between these biologics because they feel it may not make any difference? No one knows the answer to that question.
PULM CON: How else can your study findings be applied to clinical practice?
WM: Two main points: (1) Biologics are being used a lot in severe asthma patients, which is terrific. (2) However, there were a significant number of patients who were severe and were not receiving biologics. We don’t know if they could not afford it, did not qualify for it, or if these biologics are not the right ones for them (the T2 low patients).
PULM CON: What knowledge gaps still exist concerning biologic medication use for the treatment of severe asthma?
WM: Again two big needs: (1) There are no T2-low biologics for the group that needs them. We need a T2-low drug. (2) There is a group of T2-high patients not getting the available biologics for unclear reasons. We need to understand why that is and remedy it.
- Moore W, Panettieri R, Chipps B, Belton L, Trudo F, Ambrose C. Biologic medication use and switching among real-world, specialist-treated adults with severe asthma: results of the chronicle study. Talk presented at: CHEST 2020; October 18-21, 2020; Virtual. https://journal.chestnet.org/article/S0012-3692(20)32257-1/fulltext#%20