Early treatment response to mepolizumab predicts clinical remission in severe eosinophilic asthma

Abstract

Mepolizumab can induce an early response and clinical remission in people with severe eosinophilic asthma (SEA). We questioned whether early response to mepolizumab could predict future asthma remission, and sought to identify the best predictor of treatment response to mepolizumab for achieving remission. 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 Asthma Control Questionnaire (ACQ)-5, oral corticosteroid (OCS) dose, exacerbation frequency, and post-bronchodilator FEV1. Clinical remission, assessed at 12 months, was defined as ACQ-5 ≤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 (AUC) for internal validation. 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 post-bronchodilator FEV1 at 6 months was more predictive of achieving remission than measures at 3 months. ACQ-5 score at 6 months had the highest optimism-corrected AUC of 0.778 [95% CI: 0.719-0.833]. ACQ-5 score <1.5 at 6 months had a sensitivity of 85.9% for achieving clinical remission, while ACQ-5 score <0.75 had a specificity of 84.7%. 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, where treatment response is assessed at 6 months to predict clinical remission.