Conflict of interest
This work was supported in part by a grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology to R.T.M. (15K09777) and N.K. (15K09776).
Severe EPI-001 Supplier is defined by the Japanese Asthma Guidelines and Global Initiative for Asthma (GINA) guidelines as asthma requiring high-dose inhaled corticosteroids (ICS) and a second controller medication and/or oral corticosteroids (OCS) for symptom control, or disease that remains uncontrolled despite these therapies. The proportion of Japanese patients with asthma characterized as severe is reported to range from 5.7% to 7%, which is similar to the incidence in western countries (5–10%). Severe asthma is a heterogeneous condition, and a subset of patients include those with increased eosinophils, termed severe eosinophilic asthma. These patients experience frequent exacerbations, poor symptom control, decreased quality of life (QoL), and increased risk of lung function decline despite high doses of standard maintenance therapies such as ICS.
Mepolizumab is a humanized monoclonal antibody targeting interleukin-5. In clinical trials, mepolizumab has been shown to reduce eosinophil counts, the number of asthma exacerbations, and OCS maintenance dose in patients with severe eosinophilic asthma compared with placebo, when used as add-on therapy to standard of care (SoC). The global Phase III MENSA trial was conducted in Australia, East Asia, Europe, North America, and South America. It demonstrated that both mepolizumab 75 mg intravenous (IV) and 100 mg subcutaneous (SC) treatment resulted in similar reductions in the rate of clinically significant asthma exacerbations, increased lung function, and improved QoL compared with placebo, when used as add-on therapy to SoC.
For the majority of licensed pharmacological therapies, inter-ethnic differences likely to affect treatment responses have been rarely identified. Moreover, the profiles of the majority of monoclonal antibody therapies have demonstrated limited therapeutically relevant ethnic differences, with most licensed doses being the same in Japan and the USA. However, differences in patient characteristics between ethnic groups could alter therapeutic responses. Currently, there are data on the pharmacodynamics but no reports on the clinical efficacy and safety of mepolizumab in Japanese patients. Therefore, the objective of this subanalysis was to describe the efficacy and safety of mepolizumab in the Japanese subgroup of patients with severe eosinophilic asthma from the MENSA trial.
This is the first report evaluating the efficacy and safety of mepolizumab in Japanese patients with severe eosinophilic asthma. As seen in the overall population the results in the Japanese population demonstrate the efficacy of mepolizumab administered both IV and SC in reducing the number of clinically significant asthma exacerbations, improving lung function, QoL and asthma control, decreasing blood eosinophil counts. A favorable safety profile with mepolizumab was also demonstrated. These results suggest that there is no clinically relevant inter-ethnic difference in the response to mepolizumab.
Of interest, eosinophil counts were higher at baseline in the Japanese subgroup (420 cells/μL) compared with the overall population (290 cells/μL). It has been established that increased eosinophil counts are associated with an increased occurrence of asthma exacerbations. Accordingly, in the current study the higher baseline eosinophil counts in the Japanese subgroup were associated with a higher number of exacerbations in the previous year than in the overall population. This suggests that patients in the Japanese subgroup had more severe disease. However, OCS use at baseline was lower in the Japanese subgroup than in the overall population, which may also have contributed to the higher eosinophil counts and the greater number of exacerbations in the previous year.
Conflict of interest