Autor:innen:
U. von Arnim (Magdeburg, DE)
M. Chehade (New York, NY, US)
E. Dellon (Chapel Hill, NC, US)
J. Spergel (Philadelphia, PA, US)
M. Rothenberg (Cincinnati, OH, US)
R. Pesek (Little Rock, AR, US)
M. Collins (Cincinnati, OH, US)
I. Hirano (Chicago, IL, US)
R. Liu (Tarrytown, NY, US)
E. Laws (Bridgewater, NJ, US)
E. Mortensen (Tarrytown, NY, US)
R. Abdulai (Cambridge, MA, US)
J. Maloney (Tarrytown, NY, US)
E. McCann (Tarrytown, NY, US)
M. Kosloski (Tarrytown, NY, US)
J. Hamilton (Tarrytown, NY, US)
C. Samuely (Tarrytown, NY, US)
L. Glotfelty (Bridgewater, NJ, US)
A. Shabbir (Tarrytown, NY, US)
Background: There are no approved treatments for eosinophilic esophagitis (EoE) in children aged < 12 years. Dupilumab blocks key drivers of type 2 inflammation and is approved for EoE in patients (pts) aged ≥ 12 years and weight ≥ 40 kg. The Phase 3 EoE KIDS trial (NCT04394351) evaluated efficacy and safety of dupilumab vs placebo in pts aged 1 to < 12 years with EoE.
Methods: Part A was a 16 week (W) placebo-controlled study; pts were randomized 2:2:1:1 to weight-tiered, subcutaneous dupilumab on a higher-exposure (HE) or lower-exposure (LE) regimen, or 2 placebo groups to receive HE or LE dupilumab in Part B; pts who completed Part A could enter Part B, in which pts continued the same dupilumab regimen and pts on placebo switched to their pre-assigned dupilumab dose to W52. This analysis includes pts assigned to HE dupilumab and placebo.
Results: All groups had similar baseline demographics, disease characteristics, and a high level of atopic co-morbidities. At W16 in Part A, the HE dupilumab group met the primary endpoint of peak esophageal intraepithelial eosinophil (eos) count ≤ 6 eos/high-power field (hpf) vs placebo (least squares mean difference vs placebo [95% CI], 64.5 [48.19, 80.85], P < 0.0001). At W52, 62.9% of pts receiving HE in Parts A and B and 52.9% of pts who switched from placebo in Part A to HE dupilumab in Part B achieved peak eos/hpf ≤ 6. At W16, the following measures improved from baseline with HE dupilumab vs placebo: EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs +0.02 and +0.05, both P < 0.0001); EoE-Endoscopic Reference Score (–3.5 vs +0.3, P < 0.0001); change in body weight for age percentile (+3.09 vs +0.29); and numeric improvement in caregiver-reported proportion of days experiencing ≥ 1 EoE symptom/sign (-0.28 vs -0.17). At W52 in Part B, improvement in these endpoints was maintained or increased with continued HE dupilumab. Improvements were also observed in placebo pts switching to HE dupilumab (Table). The lower-exposure dupilumab regimen maintained improvements achieved in histologic, symptomatic, and endoscopic measures after 52 weeks of treatment; however, effects were generally either comparable or numerically lower with the lower-exposure dupilumab regimen than with the higher-exposure dupilumab regimen. At W16, adverse events more frequent with dupilumab vs placebo included COVID-19, rash, headache, and injection site erythema; safety profile was similar through W52.
Conclusions: HE dupilumab met the primary endpoint of peak esophageal intraepithelial eos count ≤ 6 eos/hpf vs placebo and demonstrated significant and clinically meaningful changes in histologic and endoscopic outcomes, and improvements in clinical symptoms and rate of weight gain. Benefits were maintained or increased to W52 with continued treatment.