Autor:innen:
A. Madisch (Frankfurt, DE)
E. Dellon (Chapel Hill, NC, US)
I. Hirano (Chicago, IL, US)
A. Lucendo (Tomelloso, ES)
C. Schlag (Munich, DE)
X. Sun (Tarrytown, NY, US)
L. Glotfelty (Bridgewater, NJ, US)
J. Maloney (Tarrytown, NY, US)
E. Laws (Bridgewater, NJ, US)
E. Mortensen (Tarrytown, NY, US)
A. Shabbir (Tarrytown, NY, US)
Introduction: Swallowed topical corticosteroids (STC) are a treatment option for eosinophilic esophagitis (EoE); however, they are associated with side effects and some patients (pts) may not respond. Dupilumab demonstrated improvements in histologic, symptomatic, and endoscopic features in adult and adolescent pts with EoE over 24 weeks (Phase 3 LIBERTY EoE TREET study, NCT03633617) and is approved in the US and EU for the treatment of EoE. Here we assess the effect of long-term dupilumab on histologic, symptomatic, and endoscopic aspects of EoE in pts with/without prior use of STC and with/without prior inadequate response, intolerance, or contraindication to STC.
Methods: In Part B, pts received dupilumab 300 mg or placebo weekly (qw) for 24 weeks (W24). Eligible pts who completed Part B entered Part C and received dupilumab 300 mg qw for 28 weeks (W52). Clinicians categorized pts as with/without prior STC use and with/without prior inadequate response, intolerance, or contraindication to STC at screening. Assessed outcomes were: proportion of pts achieving ≤ 6 and < 15 eosinophils per high-power field (eos/hpf), absolute change in Dysphagia Symptom Questionnaire (DSQ) score, mean change in Endoscopic Reference Score (EREFS), and Histologic Scoring System (HSS) grade/stage scores.
Results: In Part B, 80 pts received dupilumab and 79 placebo; in Part C, 74 continued dupilumab and 37 switched from placebo to dupilumab. Among pts who enrolled in Part C from Part B, 70% (78/111) had prior STC use. At W24, dupilumab improved vs placebo proportion of pts achieving ≤ 6 eos/hpf (with prior STC use 69% vs 7%, without 57% vs 0%), < 15 eos/hpf (92% vs 11%, 83% vs 0%), and DSQ score (absolute mean [SD] change -27.3 [-15.8] vs -13.6 [12.5], -23.1 [15.6] vs -19.6 [15.0]). Pts continuing dupilumab in Part C further improved at W52: proportion achieving ≤ 6 eos/hpf (with prior STC use 86%, without 81%) and DSQ score (absolute mean [SD] change 31.4 [15.8], 27.7 [14.6]); all pts achieved < 15 eos/hpf regardless of prior STC use. Pts switching from placebo to dupilumab at W24 improved at W52: proportion achieving ≤6 eos/hpf (with 70%, without 60%), < 15 eos/hpf (82%, 70%), and DSQ score ( 26.1 [12.6], 29.9 [8.4]). At W52, EREFS and HSS grade/stage scores further improved or were maintained in pts continuing dupilumab and improved in pts switching to dupilumab (Table). Similar results were observed in pts with/without prior inadequate response, intolerance, or contraindication to STC. Effects were consistent regardless of the type of STC with which patients were treated (budesonide or fluticasone).
Conclusions: Dupilumab 300 mg qw for 52 weeks led to histologic remission (< 6 eos/hpf) and sustained improvements in histologic, symptomatic, and endoscopic aspects of EoE, regardless of prior use or inadequate response, intolerance, or contraindication to STC.