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Early Treatment Response to Mepolizumab Predicts Clinical Remission in Severe Eosinophilic Asthma
Yuto Hamada1, Peter G Gibson2, Erin S Harvey2
1Center of Excellence in Treatable Traits, College of Health, Medicine and Wellbeing, University of Newcastle, New Lambton Heights, New South Wales, Australia; Asthma and Breathing Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia; Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.
Background:
Mepolizumab can induce an early response and clinical remission in people with severe eosinophilic asthma (SEA).
Objective:
To find whether early response to mepolizumab (100 mg) could predict future asthma remission and to identify the best predictor of treatment response to mepolizumab for achieving remission.
Methods:
The Australian Mepolizumab Registry was used to investigate the early response to mepolizumab at 3 and 6 months and relate this to clinical remission at 12 months. Treatment response was assessed using the 5-item Asthma Control Questionnaire (ACQ-5), oral corticosteroid (OCS) dose, exacerbation frequency, and postbronchodilator FEV1. Clinical remission, assessed at 12 months, was defined as an ACQ-5 score less than or equal to 1.0 at 12 months, no exacerbations in the previous 6 months, and no OCS use for asthma in the previous 6 months. We estimated the optimism-corrected area under the curve for internal validation.
Results:
We analyzed 255 participants with SEA. Seventy-eight (30.6%) participants achieved clinical remission at 12 months. A prediction model including ACQ-5 score, exacerbation frequency, OCS dose, and postbronchodilator FEV1 at 6 months was more predictive of achieving remission than measures at 3 months. The ACQ-5 score at 6 months had the highest optimism-corrected area under the curve of 0.778 (95% CI, 0.719-0.833). An ACQ-5 score less than 1.5 at 6 months had a sensitivity of 85.9% for achieving clinical remission, whereas an ACQ-5 score less than 0.75 had a specificity of 84.7%.
Conclusions:
The ACQ-5 score at 6 months was the best predictor of achieving clinical remission at 12 months in people with SEA treated with mepolizumab. These results can be used to design a treat-to-target paradigm for asthma, in which treatment response is assessed at 6 months to predict clinical remission.
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