P203 Effectiveness of anti-IL4R therapy following Suboptimal Response to anti-IL5/5R therapy in severe eosinophilic asthma

Abstract

<h3>Introduction</h3> Dupilumab is an anti-IL4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). We previously reported that a suboptimal response to the eosinophil-targeting anti-IL5/5R mAbs mepolizumab and benralizumab is seen in 27% and 14% of patients with SEA respectively.^1,2 The mechanism of this is not well-understood. It is unknown whether such patients respond in a clinically meaningful way following a switch to dupilumab. <h3>Methods</h3> We performed a retrospective analysis of the clinical effectiveness of dupilumab (minimum 6 months treatment) in patients with SEA at our tertiary severe asthma centre who had failed to adequately respond to at least one of the anti-IL-5/5R mAbs. Change in the annualised exacerbation rate (AER), maintenance oral corticosteroids (mOCS) requirements and ACQ-6 was recorded. <h3>Results</h3> Twenty-one patients (mean age 43.5, 71% female, 70% atopic) were included in the analysis. 9/21(42.9%) had co-morbid nasal polyposis and 3/21(14.3%) had eczema. The baseline FeNO was 62.5(38–87)ppb. 15/21 were switched from benralizumab (including 7/15 who had previously failed mepolizumab); 5/21 from mepolizumab and 1/21 from reslizumab. 3/21 had previously failed omalizumab prior to a switch to an anti-IL5/5R mAb. Fifteen patients were receiving mOCS at the time of commencing dupilumab. At six months, the daily median mOCS dose fell from 10mg (6.25–22.5mg) to 3mg (0–7.5mg), P&lt;0.002. ACQ-6 improved by 1.04 units from 2.94±1.31 to 1.90±1.40, p=0.037. There was a trend towards improvement in AER from 1.56±1.50 to 0.75±1.24, p=0.063. Median blood eosinophil count rose from 0.0(0–0.2) to 0.5(0.3–1.2), p&lt;0.001. One patient discontinued dupilumab during the follow-up period. <h3>Conclusion</h3> A minority of individuals with SEA have a suboptimal response to eosinophil-targeted therapy with an anti-IL5/5R mAb. We report significant clinical improvements following initiation with dupilumab suggesting an important role for IL-4/-13 in these patients. The exact mechanisms require further research and are likely to lead to a reclassification of T2-high sub-phenotypes. <h3>References</h3> Kavanagh JE, d’Ancona G, Elstad M, <i>et al</i>. Real-world effectiveness and the characteristics of a ‘super-responder’ to mepolizumab in severe eosinophilic asthma. <i>Chest</i>. 2020Aug;158(2):491–500. Kavanagh JE, Hearn AP, Dhariwal J, <i>et al</i>. Real-world effectiveness of benralizumab in severe eosinophilic asthma. <i>Chest</i>. 2021;159(2):496–506.