Reliability of histologic assessment in patients with eosinophilic oesophagitis

Warners, Marijn J.; Ambarus, Carmen A.; Bredenoord, Albert J.; Verheij, Joanne; Lauwers, Greg Y.; Walsh, Joanna; Katzka, David A.; Nelson, Suzanne; Viegen, Tanja van; Furuta, Glenn T.; Gupta, Sandeep K.; Stitt, Larry; Zou, Guangyong; Parker, Claire E; Shackelton, Lisa M.; DʼHaens, G; Sandborn, William J.; Dellon, Evan S.; Feagan, Brian G.; Collins, Margaret H.; Jairath, Vipul; Pai, Rish K.

doi:10.1111/apt.14559

Cited by 52 publications

(36 citation statements)

References 24 publications

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“…6,39 In addition, dupilumab improved most components of the EoE-HSS, a recently validated histologic score that measures other histologic abnormalities in addition to the density of eosinophilic inflammation. 38,42 Significant improvements in EEsAI PRO symptom score vs placebo were also observed with dupilumab treatment, which supported the histologic findings of decreased esophageal eosinophilia and increased distensibility with dupilumab treatment, consistent with a reduction in remodeling and improved esophageal function. 39 These results show that IL4 and IL13 are central pathologic mediators of esophageal inflammation and dysfunction in adult patients with active EoE.…”

supporting

confidence: 52%

Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis

et al. 2020

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supporting

confidence: 52%

Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis

et al. 2020

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“…cells, and lamina propria fibrosis (Supplementary Material). 19,20 Adverse events and concomitant medication use were recorded through 16 weeks (24 weeks for patients who did not continue into the open-label extension). Blood samples were obtained at each clinic visit for clinical chemistry and hematology, serum RPC4046 assessment, and serum antibodies to RPC4046.…”

Section: Methodsmentioning

confidence: 99%

RPC4046, a Monoclonal Antibody Against IL13, Reduces Histologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis

et al. 2019

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Primary Outcome Esophageal eosinophil count: P < .0001 for both dose groups Key Secondary Outcome Dysphagia clinical symptom frequency and severity (DSD): Not statistically significant for both dose groups Safety Assessment AEs All low frequency Headache Upper respiratory tract infection Arthralgia Nasopharyngitis Diarrhea Nausea SAEs All unrelated to treatment RPC4046 180 mg or 360 mg treatment for 16 weeks See editorial on page 545. BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic, esophageal, type 2 inflammatory response associated with increased serum levels of interleukin 13 (IL13), which might contribute to its pathogenesis. RPC4046, a recombinant humanized monoclonal antibody against IL13, prevents its binding to the receptor subunits IL13RA1 and IL13RA2. We performed a phase 2 trial to evaluate the efficacy and safety of RPC4046 in patients with EoE. METHODS: We performed a multicenter, double-blind trial of 99 adults with active EoE randomly assigned (1:1:1) to groups given RPC4046 (180 or 360 mg) or placebo once weekly for 16 weeks, from September 2014 through December 2015. Patients were seen at day 1 (baseline) and weeks 2, 4, 8, 12, and 16. They underwent esophagogastroduodenoscopy and biopsies were collected at baseline and week 16. Patients completed a daily dysphagia symptom diary through week 16 and patient-reported outcome data were collected. The primary outcome was change in mean esophageal eosinophil count in the 5 high-power fields (hpfs) with the highest level of inflammation. RESULTS: At week 16, mean changes in esophageal eosinophil count per hpf were a reduction of 94.8 ± 67.3 in patients who received 180 mg RPC4046 (P < .0001) and a reduction of 99.9 ± 79.5 in patients who received 360 mg RPC4046 (P < .0001) compared with a reduction of 4.4 ± 59.9 in patients who received placebo. The 360-mg RPC4046 group, compared with the placebo group, showed significant reductions in validated endoscopic severity score at all esophageal locations (P < .0001), validated histologic grade and stage scores (both P < .0001), and clinician's global assessment of disease severity (P ¼ .0352); they had a numerical reduction in scores from the dysphagia symptom diary (P ¼ .0733). Significant reductions in esophageal

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“…The authors’ declarations of personal and financial interests are unchanged from those in the original article …”

Section: Acknowledgementsmentioning

confidence: 99%

“…We thank Drs. Connor and Kirsch for their editorial highlighting challenges in the investigation of eosinophilic oesophagitis (EoE), a condition considered uncommon only a decade ago that has since increased in incidence such that it is now commonly encountered in community practice . Until recently, there were no approved medical therapies for EoE due to want of pharmaceutical industry investment, lack of validated outcome measures and absence of a clear regulatory pathway for drug approval.…”

mentioning

confidence: 99%

Editorial: validating reliability of the eosinophilic oesophagitis histological scoring system (EOE‐HSS)—an important first step. Authors’ reply

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Feagan

et al. 2018

Aliment Pharmacol Ther

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Reliability of histologic assessment in patients with eosinophilic oesophagitis

Abstract: SummaryBackground: The validity of the eosinophilic oesophagitis (EoE) histologic scoring

Cited by 52 publications

References 24 publications

Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis

Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis

RPC4046, a Monoclonal Antibody Against IL13, Reduces Histologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis

Editorial: validating reliability of the eosinophilic oesophagitis histological scoring system (EOE‐HSS)—an important first step. Authors’ reply

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