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Abstract
Objective We aimed to determine whether mepolizumab, an anti-IL-5 antibody, was more effective than placebo for improving dysphagia symptoms and decreasing oesophageal eosinophil counts in eosinophilic oesophagitis (EoE).
Methods We conducted a multicentre, randomised, double-blind, placebo-controlled, trial. In the first part, patients aged 16–75 with EoE and dysphagia symptoms (per EoE Symptom Activity Index (EEsAI)) were randomised 1:1 to 3 months of mepolizumab 300 mg monthly or placebo. Primary outcome was change in EEsAI from baseline to month 3 (M3). Secondary outcomes included histological, endoscopic and safety metrics. In part 2, patients initially randomised to mepolizumab continued 300 mg monthly for 3 additional months (mepo/mepo), placebo patients started mepolizumab 100 mg monthly (pbo/mepo), and outcomes were reassessed at month 6 (M6).
Results Of 66 patients randomised, 64 completed M3, and 56 completed M6. At M3, EEsAI decreased 15.4±18.1 with mepolizumab and 8.3±18.0 with placebo (p=0.14). Peak eosinophil counts decreased more with mepolizumab (113±77 to 36±43) than placebo (146±94 to 160±133) (p<0.001). With mepolizumab, 42% and 34% achieved histological responses of <15 and ≤6 eos/hpf compared with 3% and 3% with placebo (p<0.001 and 0.02). The change in EoE Endoscopic Reference Score at M3 was also larger with mepolizumab. At M6, EEsAI decreased 18.3±18.1 points for mepo/mepo and 18.6±19.2 for pbo/mepo (p=0.85). The most common adverse events were injection-site reactions.
Conclusions Mepolizumab did not achieve the primary endpoint of improving dysphagia symptoms compared with placebo. While eosinophil counts and endoscopic severity improved with mepolizumab at 3 months, longer treatment did not yield additional improvement.
Trial registration number NCT03656380.
- OESOPHAGEAL DISEASE
- CLINICAL TRIALS
- HISTOPATHOLOGY
- DYSPHAGIA
Data availability statement
Data are available on reasonable request. Data may be shared after all planned analyses have been completed, and with required approvals in place.
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Data availability statement
Data are available on reasonable request. Data may be shared after all planned analyses have been completed, and with required approvals in place.
Footnotes
Contributors All authors approved the final manuscript. ESD: project conception, study design, data collection, data analysis/interpretation, manuscript drafting, critical revision, obtained funding, guarantor. KAP, BLM and IH: data collection, data interpretation, critical revision. AI, CB and JTW: data collection, study pathologist, data interpretation, critical revision. LMC, KBW, TSG, SJM, BAC and SEM: data collection and management, monitoring, critical revision. JAG: study design, data analysis/interpretation; critical revision. SE: data collection, data interpretation, monitoring, critical revision.
Funding This study was supported by an investigator-initiated research grant from GlakoSmithKline (GSK ISS 209033), and used resources from UNC Center for GI Biology and Disease (NIH P30 DK034987), NC TraCS, which is funded by the National Center for Advancing Translational Sciences (NCATS) Clinical and Translation Science Award (UM1TR004406), and the UNC Pathology Services Core, which is supported in part by an NCI Center Core Support Grant (P30 CA016086), and the North Carolina Translational and Clinical Sciences Institute which is supported by the National Center for Advancing Translational Sciences (NCATS; NIH UL1TR002489).
Disclaimer The study sponsor did not have any role in the study design or in the collection, analysis, or interpretation of the data.
Competing interests ESD has received research funding from Adare/Ellodi, Allakos, Arena, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Shire/Takeda; consulting fees from Abbott, Abbvie, Adare/ Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio; and educational grants from Allakos, Holoclara, Invea. IH has received research funding from Adare/Ellodi, Allakos, Arena, AstraZeneca, Meritage, Celgene/Receptos/BMS, Regeneron, Shire/Takeda; consulting fees from Adare/ Ellodi, Allakos, Amgen, Arena/Pfizer, Aslan, AstraZeneca, Celgene/Receptos/BMS, Celldex, EsoCap, Gossamer Bio, Nexstone Immunology, Parexel/Calyx, Phathom, Regeneron, Sanofi, Shire/Takeda. KAP has received research funding from AstraZeneca, Allakos, Adare, Regeneron-Sanofi, Revolo,; Speaker: AGA, Regeneron, Peerview, Takeda, Allakos, WebMD; unrestricted grant support from Allakos, Chobani; consulting or advisory board fees from AGA, Alladapt, AstraZeneca, Allakos, Bristol Meyers Squibb, Ellodi, Invea, Lucid, Nexstone, WebMD, Peerview, Regeneron, Revolo, Takeda, WebMD; and has equity in Nexeos Bio. The other authors report no relevant disclosures.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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