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. 2024 Jul;12(7):1794-1800.
doi: 10.1016/j.jaip.2024.03.049. Epub 2024 Apr 5.

Long-Term Effectiveness of Anti-IL-4R Therapy Following Suboptimal Response to Anti-IL-5/5R Therapy in Severe Eosinophilic Asthma

Jessica Gates  1 , Andrew Hearn  1 , Tom Mason  2 , Mariana Fernandes  2 , Linda Green  2 , Louise Thomson  2 , Cris Roxas  2 , Jodie Lam  2 , Grainne d'Ancona  2 , Alexandra M Nanzer  1 , Jaideep Dhariwal  2 , David J Jackson  3
Affiliations

Long-Term Effectiveness of Anti-IL-4R Therapy Following Suboptimal Response to Anti-IL-5/5R Therapy in Severe Eosinophilic Asthma

Jessica Gates et al. J Allergy Clin Immunol Pract. 2024 Jul.

Abstract

Background: Dupilumab is an anti-IL-4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). A suboptimal response to anti-IL-5/5R mAbs is seen in some patients with ongoing evidence of type 2 (T2) inflammation.

Objective: To understand whether targeting IL-13 pathways with dupilumab in these patients may lead to better clinical outcomes.

Methods: We performed a retrospective analysis of the extended clinical effectiveness of dupilumab up to 2 years of treatment in patients with SEA who had not responded adequately to anti-IL-5/5R biologics. The ability to achieve clinical remission and the change in the remission domains of exacerbation rate (AER), maintenance oral corticosteroid dose (mOCS), lung function (forced expiratory volume in 1 second), and asthma control (Asthma Control Questionnaire 6) were recorded.

Results: Thirty-seven patients (mean age 41 years, 70% female) were included in the analysis. The mean (standard deviation) AER fell by almost 90% from 3.16 (1.28) at dupilumab initiation to 0.35 (0.72) after 1 year. The median (interquartile range) mOCS dose (n = 20) fell from 10 (5-25) mg to 0 (0-5) mg at 1 year, with 14 of 20 (70%) able to stop prednisolone altogether. Clinical remission was achieved in 16 of 37 (43%). Patients who achieved remission had a higher pre-IL-5/5R fractional exhaled nitric oxide (FeNO) level (85 [39-198] parts per billion [ppb] vs 75 [42-96] ppb, P = .03).

Conclusions: Significant improvements in clinical outcomes are possible after a switch to dupilumab in patients experiencing a suboptimal response to anti-IL-5/5R therapies. A higher FeNO in poor responders to anti-IL-5/5R who achieve remission with dupilumab is suggestive of an IL-13-driven subphenotype of T2-high asthma in which the eosinophil appears unlikely to play a key role in the disease pathogenesis.

Keywords: Asthma biologics; Asthma remission; Dupilumab; Eosinophilic asthma; Severe asthma.

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