S575 Dupilumab Efficacy in Children With Eosinophilic Esophagitis and Prior Use of or Prior Inadequate Response, Intolerance, or Contraindication to Swallowed Topical Corticosteroids: Results From the Phase 3 EoE KIDS Study

Introduction: Eosinophilic esophagitis (EoE) is a chronic type 2 inflammatory disease of the esophagus. Swallowed topical corticosteroids (STCs) are commonly used to treat EoE, but not all patients achieve remission and others may be intolerant or have contraindications. Dupilumab is approved for EoE in patients aged ≥1 year, weighing ≥15 kg, in the US. We assessed the effect of dupilumab in children aged 1 to < 12 years with EoE with prior use of or prior inadequate response (IR)/intolerance/contraindication to STCs in the Phase 3 EoE KIDS study (NCT04394351). Methods: This analysis includes patients randomized at Part A baseline to weight-tiered dupilumab higher-exposure (HE) or pooled placebo (PBO) up to Week (W) 16. Part B data were analyzed for patients who continued dupilumab HE, or switched from PBO to dupilumab HE through to W52. STC use ≤8 weeks before study baseline was prohibited. The primary endpoint was the proportion of patients achieving histologic remission (peak eosinophil count [PEC] ≤6 eosinophils/high-power field [eos/hpf]) at W16. Secondary endpoints were the proportion of patients achieving PEC < 15 eos/hpf, percent change in PEC, absolute change in Endoscopic Reference Score, EoE-Histologic Scoring System grade/stage scores, and proportion of days with ≥1 EoE sign as assessed by the Pediatric EoE Sign/Symptom Questionnaire – Caregiver version. Efficacy was assessed by prior use of or prior IR/intolerance/contraindication to STCs. Results: Of the 102 patients who entered the study, most (80.4%) had a history of STC therapy, and 57.8% had a prior IR/intolerance/contraindication to STCs. Regardless of prior STC use, dupilumab HE improved rates of histologic remission and key secondary endpoints vs PBO at W16 (Table 1). Responses were maintained at W52 in patients continuing dupilumab HE, and improved in patients who switched from PBO to dupilumab HE regardless of prior STC use, although patient numbers were small in the subgroup without prior STC use (Table 1). Similar improvements in primary and secondary endpoints were observed in patients with and without prior IR/intolerance/contraindication to STCs. Conclusion: Dupilumab HE showed sustained improvements in histologic and endoscopic aspects of EoE vs PBO, and numerical improvements in symptoms, in children with EoE regardless of prior use of or prior IR/intolerance/contraindication to STCs. Table 1. - Efficacy of dupilumab at Week 16 and Week 52 by prior STC use Week 16 Week 52 PBO (N=34) DUP HE (N = 37) PBO/DUP HE (N = 18)a DUP HE/DUP HE (N = 37)a n/NIb n/NIb n n Patients with PEC of ≤6 eos/hpf, n (%) With prior STC 27/0 0 28/0 17 (60.7) 16 8 (50.0) 26 13 (50.0) Without prior STC 4/3 1 (14.3) 9/0 8 (88.9) 1 1 (100.0) 9 9 (100.0) Patients with PEC of < 15 eos/hpf, n (%) With prior STC 27/0 0 28/0 22 (78.6) 16 10 (62.5) 26 21 (80.8) Without prior STC 4/3 1 (14.3) 9/0 9 (100.0) 1 1 (100.0) 9 9 (100.0) % change in PECc With prior STC 27/0 30.79 (13.92) 28/0 –80.34 (13.87) 16 –75.38 (42.13) 26 –89.06 (16.35) Without prior STC 4/3 –5.07 (11.05) 9/0 –91.79 (9.66) 1 –100.00 (NA) 9 –96.51 (3.11) EREFS total scorec With prior STC 22/0 0.3 (0.50) 24/2 –3.8 (0.46) 13 –3.08 (2.69) 22 –5.14 (3.30) Without prior STC 5/2 –0.7 (0.68) 8/0 –2.1 (0.63) 1 –11.00 (NA) 8 –3.75 (2.25) HSS gradec With prior STC 27/0 0.07 (0.05) 28/0 –0.91 (0.05) 16 –0.87 (0.30) 26 –1.03 (0.42) Without prior STC 4/3 –0.14 (0.09) 9/0 –0.74 (0.08) 1 –1.07 (NA) 9 –0.77 (0.23) HSS stagec With prior STC 27/0 0.06 (0.05) 28/0 –0.87 (0.05) 16 –0.85 (0.36) 26 –0.93 (0.33) Without prior STC 4/3 –0.01 (0.10) 9/0 –0.71 (0.09) 1 –1.01 (NA) 9 –0.78 (0.25) PESQ-Cc With prior STC 25/2 –0.13 (0.06) 23/4 –0.27 (0.06) 8 –0.50 (0.41) 19 –0.28 (0.34) Without prior STC 5/2 –0.27 (0.10) 8/1 –0.26 (0.09) 1 –0.22 (NA) 8 –0.37 (0.17) aNumber of patients who completed the Week 52 visit in Part B were n = 17 for PBO/DUP HE and n = 35 for DUP HE/DUP HE.bPatients with missing PEC at Week 16 were considered non-responders if not due to COVID-19, and were imputed by MI if due to COVID-19; patients with missing values for percent change from Part A baseline in PEC, and change from Part A baseline in EREFS total score, and HSS grade and stage scores were imputed by WOCF method if not due to COVID-19, and by MI if due to COVID-19; patients with missing values for change from Part A baseline in the proportion of days with ≥1 EoE sign measured by PESQ-C were imputed by WOCF method if due to rescue treatment/adverse events/lack of efficacy, and by MI if due to other reasons.cChange/percent change from Part A baseline: LS mean (SE) at Week 16; mean (SD) at Week 52.DUP, dupilumab; EoE, eosinophilic esophagitis; eos/hpf, eosinophils/high-power field; EREFS, Endoscopic Reference Score; HE, higher-exposure; HSS, Histologic Scoring System; LS, least squares; MI, multiple imputations; NA, not applicable as n=1; NI, number imputed; PBO, placebo; PEC, peak eosinophil count; PESQ-C, Pediatric EoE Sign/Symptom Questionnaire – Caregiver version; SD, standard deviation; SE, standard error; STC, swallowed topical corticosteroid; WOCF, worst observation carried forward.

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