S403 Dupilumab Reduces the Emotional and Dysphagia-Related Impacts of Eosinophilic Esophagitis to Improve Health-Related Quality of Life

Abstract

Introduction: Eosinophilic esophagitis (EoE) is a chronic, type 2 inflammatory disease of the esophagus which substantially impairs quality of life (QoL). Dupilumab, a fully human mAb, blocks the shared receptor component for IL-4/IL-13, key drivers of type 2 inflammation in EoE. In the 3-part LIBERTY-EoE-TREET phase 3 trial (NCT03633617), Parts A and B demonstrated that weekly (qw) dupilumab 300mg improved clinical, symptomatic, histologic, and endoscopic aspects of EoE and was generally well tolerated in patients (pts) ≥12 years at Wk 24. The objective of this post-hoc analysis was to assess the effect of dupilumab vs placebo on improving aspects of QoL using the EoE Impact Questionnaire (EoE-IQ), a novel disease-specific measure of health-related QoL in EoE patients, during the 24-wk double-blind treatment period in Parts A and B. Methods: In Part A, 42 pts received dupilumab 300mg qw, and 39 received placebo. In Part B, 80 pts received dupilumab 300mg qw, and 79 received placebo for 24 wks. The EoE-IQ is a patient-reported 11-item questionnaire that measures the impact of EoE on emotional, social, work and school, and sleep aspects of a patient (over a 7-day recall period). It was developed in line with best practices in the field of clinical outcomes assessment and includes the most relevant QoL impacts of EoE as identified through literature review and discussion with therapeutic area experts and confirmed via patient interviews. Response to each item is on a 5-point scale ranging from 1-5 with a higher score indicating a more negative impact on QoL. Results: The most burdensome impacts of EoE at baseline were related to overall emotional impact and anxiety around dysphagia (Table). Dupilumab showed a nominally significant reduction vs placebo in 6 items in Parts A and B: ‘bothered’, ‘worried about swallowing’, ‘worried about choking’, ‘worried about swallowing in public’, ‘social activities’, ‘sleep disruption’ (all nominal p< 0.05), and in 1 additional item in Part B (‘embarrassed’, nominal p< 0.05). The largest placebo adjusted change from baseline to Wk 24 was observed in items relating to overall emotional impact and anxiety, including ‘worried about swallowing in public’ (Part A: –0.90; Part B: –0.45), ‘bothered’ (–0.64; –0.53), ‘worried about swallowing’ (–0.73; –0.65), and ‘worried about choking’ (–0.61; –0.57). Conclusion: EoE QoL was improved among pts on dupilumab 300mg qw, with improvement driven by emotional and social impacts, and sleep. Table 1. - EoE-IQ at baseline and after 24 weeks treatment with weekly dupilumab 300mg or placebo. Values after first rescue treatment use were set to missing (censoring), then multiple imputation was used to impute missing values. Mean absolute value at baseline Mean absolute value at Week 24 EoE-IQ Item Dupilumab300 mg qw Dupilumab 300 mg qw LS Mean Difference vs placebo P value Part A 1. Bothered 3.08 1.80 –0.64 0.0043 2. Worried swallowing 2.88 1.69 –0.73 0.0011 3. Worried choking 2.42 1.60 –0.61 0.0040 4. Embarrassed 1.91 1.34 –0.21 0.2336 5. Worried swallowing public 2.80 1.46 –0.90 0.0001 6. Social activities 2.06 1.40 –0.43 0.0311 7. Family 1.44 1.29 –0.20 0.2560 8. Friends 1.39 1.28 –0.31 0.0813 9. Keep up work/school 1.48 1.30 –0.28 0.1379 10. Miss work/school 1.37 1.34 –0.09 0.5504 11. Sleep disruption 1.82 1.21 –0.42 0.0027 Part B 1. Bothered 3.50 1.97 –0.53 0.0004 2. Worried swallowing 3.10 1.60 –0.65 < 0.0001 3. Worried choking 2.72 1.45 –0.57 < 0.0001 4. Embarrassed 2.21 1.28 –0.28 0.0141 5. Worried swallowing public 2.96 1.53 –0.45 0.0020 6. Social activities 2.34 1.35 –0.30 0.0117 7. Family 1.72 1.22 0.01 0.8765 8. Friends 1.68 1.19 –0.06 0.4409 9. Keep up work/school 1.81 1.32 –0.08 0.4170 10. Miss work/school 1.32 1.18 –0.09 0.3390 11. Sleep disruption 1.94 1.36 –0.22 0.0409 EoE-IQ, Eosinophilic Esophagitis Impact Questionnaire; LS, least squares; qw, weekly.