Abstract and Introduction
Background: Several major randomized control studies have demonstrated that mepolizumab, an anti-IL-5 monoclonal antibody, is effective for patients with severe eosinophilic asthma who show exacerbation or require systemic corticosteroid maintenance therapy. However, the predictive factors of the response to mepolizumab other than blood eosinophil count are unclear in clinical practice.
Objective: To elucidate the predictive factors of the response to mepolizumab for patients with severe eosinophilic asthma.
Methods: From July 2016 to December 2017, 28 patients with severe asthma received mepolizumab in our hospital. To determine the predictive factors, we retrospectively evaluated patient characteristics, comorbidities, biomarkers, pulmonary function, maintenance dose of systemic corticosteroids and number of exacerbations.
Results: The response rate to mepolizumab treatment was 70% (19/27; one pregnant woman was excluded from analysis). Compared with 11 patients without eosinophilic chronic rhinosinusitis (ECRS), 16 patients with ECRS showed significantly improved systemic corticosteroid-sparing effects [− 71.3 ± 37.0% vs − 10.7 ± 20.1%, P = 0.006], change from baseline FeNO [− 19 ± 57 (%) vs 30 ± 77 (%), P = 0.023] and symptoms [14 patients (88%) vs five patients (45%), P = 0.033]. ECRS was identified as a predictive factor of the response to mepolizumab in a multivariate logistic regression analysis [odds ratio = 22.5, 95% CI (1.5–336), P = 0.024]. Of the eight patients previously administered omalizumab, five responded to mepolizumab. Staphylococcus aureus enterotoxin B IgE results were negative in 80% of responders (P = 0.14).
Conclusion: Both groups showed improved symptom scores and a decreased number of exacerbations. Mepolizumab substantially improved the clinical variables of patients with eosinophilic asthma complicated with ECRS.
It is estimated that as many as 300 million people of all ages and ethnic backgrounds suffer from asthma. Asthma is a common chronic respiratory disease that affects approximately 5–10% of Japanese adults.[2,3] The prevalence of severe and uncontrolled asthma among adults with asthma has been reported to be 3 to 10%. Severe asthma is associated with morbidity, mortality, and high healthcare costs. Recently, severe asthma was classified into several clinical phenotypes that differ in severity and response to therapy. Severe eosinophilic asthma is characterized by Th2 inflammation, and patients with severe eosinophilic asthma experience recurrent asthma exacerbations even when treated with high doses of inhaled corticosteroids (ICS) and controllers such as long-acting bronchodilators, leukotriene receptor antagonists and oral corticosteroids (OCS). Twenty to 25% of patients with difficult-to-control asthma have nasal polyps. Furthermore, patients with asthma and high blood eosinophil counts have poor asthma control.
IL-5, which induces the proliferation, differentiation and migration of eosinophils, plays an important role in the pathogenesis of eosinophilic asthma. Mepolizumab, a humanized monoclonal antibody against IL-5, selectively inhibits eosinophilic airway inflammation. Several major randomized control trials (RCTs) have demonstrated that this antibody reduces the number of eosinophils in both sputum and blood, resulting in reductions in exacerbations, improvements in pulmonary function and a glucocorticoid-sparing effect in patients with uncontrolled asthma and a peripheral blood eosinophil count ≥150/mm3 at baseline or ≥ 300/mm3 during the previous year.[11–13] Although previous reports have demonstrated the efficacy of this treatment in patients with severe eosinophilic asthma, patients who meet the criteria of eosinophil counts do not always respond to mepolizumab. Accordingly, the identification of predictive factors of a response is very important from a medical economic perspective. However, few reports have examined the predictive factors for mepolizumab; these have been limited to RCTs and their subgroup analyses[11,14] and a cluster analysis of the response to mepolizumab. The reported main distinctive features of patients with good response are blood eosinophilia ≥150/mm3, airway reversibility > 16.2% and a body mass index (BMI) ≥30 kg/m2. BMI has been reported to be lower in Japanese patients with asthma than in Caucasian ones. To elucidate the clinical efficacy of mepolizumab in Japanese patients with severe asthma, we performed a single-center, retrospective study.
BMC Pulm Med. 2019;19(176) © 2019 BioMed Central, Ltd.