Early Treatment Response to Mepolizumab Predicts Clinical Remission in Severe Eosinophilic Asthma

Yuto Hamada; Peter G Gibson; Erin S Harvey; Sean Stevens; Hayley Lewthwaite; Michael Fricker; Vanessa M McDonald; Andrew Gillman; Mark Hew; Vicky Kritikos; John W Upham; Dennis Thomas

doi:10.1016/j.jaip.2024.10.041

Early Treatment Response to Mepolizumab Predicts Clinical Remission in Severe Eosinophilic Asthma

J Allergy Clin Immunol Pract. 2024 Nov 6:S2213-2198(24)01160-7. doi: 10.1016/j.jaip.2024.10.041. Online ahead of print.

Authors

Affiliations

¹ Center 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. Electronic address: [email protected].
² Center 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; Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, New South Wales, Australia.
³ Center of Excellence in Treatable Traits, College of Health, Medicine and Wellbeing, University of Newcastle, New Lambton Heights, New South Wales, Australia.
⁴ Center 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.
⁵ Asthma and Breathing Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
⁶ Allergy, Asthma and Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia.
⁷ Allergy, Asthma and Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
⁸ Clinical Management Group, Woolcock Institute of Medical Research, Sydney, New South Wales, Australia.
⁹ Department of Respiratory Medicine, Princess Alexandra Hospital, Brisbane, Queensland, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

PMID: 39515519
DOI: 10.1016/j.jaip.2024.10.041

Abstract

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.

Keywords: Clinical remission; Early response; Eosinophilic asthma; Mepolizumab; Treat-to-target.