Age and age-of-onset of asthma influence mepolizumab eligibility
Published online: June 12, 2019
Severe asthma (SA), while comprising only 5 to 10% of all asthma, is responsible for the majority of asthma-related deaths, Emergency Department/Urgent Care visits, and healthcare costs despite maximal medical therapy - including high dose inhaled, and often chronically administered oral corticosteroids (OCS) in addition to other controller agents. SA can be grouped into 2 major categories or phenotypes, based on the type of underlying airway inflammation. Type-2 high asthma is characterized by an influx of T helper type 2 cells (TH2) and eosinophils into the airway, and can be associated with allergy (elevated total and specific IgE levels), while Type-2 low asthma is associated with T helper type-1 and type-17 (TH1 and TH17) cells and/or neutrophils. Over the past decade, biological therapies such as mepolizumab have been developed that target Type 2-high inflammation. Mepolizumab, a humanized monoclonal antibody, acts by neutralizing interleukin (IL)-5, a critical cytokine involved in eosinophil proliferation, survival, and activation. Mepolizumab has been shown to be effective in reducing asthma exacerbations and improving asthma control. However, the proportion of severe asthmatics eligible for treatment with mepolizumab remains poorly understood, especially among children with SA.
In a recent article published in The Journal of Allergy and Clinical Immunology: In Practice, Dr. Comberiati and colleagues sought to determine the proportion of Type-2 high severe asthmatics eligible for mepolizumab when stratified for by age (child vs. adult) and the age-of-onset of asthma (childhood vs. adult-onset asthma). An extensive database from a national referral center was used to identify 216 adults and children (6 to 17 years) who met the European Respiratory Society (ERS)/American Thoracic Society (ATS) criteria for SA. To be eligible for mepolizumab, patients had to have type 2-high asthma as measured by a blood eosinophil count of ≥150 cells/uL, ≥2 exacerbations requiring OCS in the past year, and ≥12 years old. Based on blood eosinophils ≥150 cells/uL, 61% had type-2 high asthma, while 49% were eligible for mepolizumab therapy. A greater percentage of adults (60% with asthma onset in adulthood [AoA] and 48% adults with childhood-onset asthma, [CoA]) were eligible compared to 33% of children with SA. If all children were included, the percentage eligible rose substantially to 56%. Children were as likely to have frequent exacerbations, while having less lung function impairment compared to the adults with SA. Among adults, those with AoA were more likely to have nasal polyps and had higher blood eosinophil counts compared to adults with CoA.
In summary, up to 60% of adults with SA would be eligible for mepolizumab therapy with a smaller proportion of children with SA being eligible. This discrepancy comes from the fact that only children 12 to 17 years of age were eligible. If children 6 years to 17 years of age were included (mepolizumab is approved for use in children ≥6 years of age in Europe), the percentage of eligible children increased substantially. Among adults, those with AoA have features which most favour treatment with mepolizumab, including greater eosinophilia and nasal polyposis compared to adults with CoA. As children often have concurrent allergy and eosinophilia or either alone, further studies evaluating mepolizumab in children should be performed to be determine the response profile of anti-IL-5 targeted therapies in this group of SA.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.