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

HEROES Study Group

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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 =.0352); they had a numerical reduction in scores from the dysphagia symptom diary (P =.0733). Significant reductions in esophageal eosinophil counts and histologic and endoscopic features were observed in patients with steroid-refractory EoE who received RPC4046. The most common adverse events were headache and upper respiratory tract infection. Conclusions: In a phase 2 trial of patients with EoE, we found RPC4046 (a monoclonal antibody against IL13) to reduce histologic and endoscopic features compared with placebo. RPC4046 was well tolerated. ClinicalTrials.gov no: NCT02098473.

Original languageEnglish (US)
Pages (from-to)592-603.e10
JournalGastroenterology
Volume156
Issue number3
DOIs
StatePublished - Feb 1 2019

Fingerprint

Eosinophilic Esophagitis
Interleukin-13
Monoclonal Antibodies
Placebos
Eosinophils
Deglutition Disorders
Digestive System Endoscopy
Antibodies, Monoclonal, Humanized
Respiratory Tract Infections
Headache
Steroids
Inflammation
Biopsy
Safety

Keywords

  • Esophagus
  • Immune Response
  • Placebo-Controlled
  • Randomized

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

RPC4046, a Monoclonal Antibody Against IL13, Reduces Histologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis. / HEROES Study Group.

In: Gastroenterology, Vol. 156, No. 3, 01.02.2019, p. 592-603.e10.

Research output: Contribution to journalArticle

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abstract = "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 =.0352); they had a numerical reduction in scores from the dysphagia symptom diary (P =.0733). Significant reductions in esophageal eosinophil counts and histologic and endoscopic features were observed in patients with steroid-refractory EoE who received RPC4046. The most common adverse events were headache and upper respiratory tract infection. Conclusions: In a phase 2 trial of patients with EoE, we found RPC4046 (a monoclonal antibody against IL13) to reduce histologic and endoscopic features compared with placebo. RPC4046 was well tolerated. ClinicalTrials.gov no: NCT02098473.",
keywords = "Esophagus, Immune Response, Placebo-Controlled, Randomized",
author = "{HEROES Study Group} and Ikuo Hirano and Collins, {Margaret H.} and Yehudith Assouline-Dayan and Larry Evans and Sandeep Gupta and Schoepfer, {Alain M.} and Alex Straumann and Ekaterina Safroneeva and Michael Grimm and Heather Smith and Tompkins, {Cindy ann} and Amy Woo and Robert Peach and Paul Frohna and Sheila Gujrathi and Penenberg, {Darryl N.} and Caiyan Li and Opiteck, {Gregory J.} and Allan Olson and Richard Aranda and Rothenberg, {Marc E.} and Dellon, {Evan S.}",
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TY - JOUR

T1 - RPC4046, a Monoclonal Antibody Against IL13, Reduces Histologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis

AU - HEROES Study Group

AU - Hirano, Ikuo

AU - Collins, Margaret H.

AU - Assouline-Dayan, Yehudith

AU - Evans, Larry

AU - Gupta, Sandeep

AU - Schoepfer, Alain M.

AU - Straumann, Alex

AU - Safroneeva, Ekaterina

AU - Grimm, Michael

AU - Smith, Heather

AU - Tompkins, Cindy ann

AU - Woo, Amy

AU - Peach, Robert

AU - Frohna, Paul

AU - Gujrathi, Sheila

AU - Penenberg, Darryl N.

AU - Li, Caiyan

AU - Opiteck, Gregory J.

AU - Olson, Allan

AU - Aranda, Richard

AU - Rothenberg, Marc E.

AU - Dellon, Evan S.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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 =.0352); they had a numerical reduction in scores from the dysphagia symptom diary (P =.0733). Significant reductions in esophageal eosinophil counts and histologic and endoscopic features were observed in patients with steroid-refractory EoE who received RPC4046. The most common adverse events were headache and upper respiratory tract infection. Conclusions: In a phase 2 trial of patients with EoE, we found RPC4046 (a monoclonal antibody against IL13) to reduce histologic and endoscopic features compared with placebo. RPC4046 was well tolerated. ClinicalTrials.gov no: NCT02098473.

AB - 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 =.0352); they had a numerical reduction in scores from the dysphagia symptom diary (P =.0733). Significant reductions in esophageal eosinophil counts and histologic and endoscopic features were observed in patients with steroid-refractory EoE who received RPC4046. The most common adverse events were headache and upper respiratory tract infection. Conclusions: In a phase 2 trial of patients with EoE, we found RPC4046 (a monoclonal antibody against IL13) to reduce histologic and endoscopic features compared with placebo. RPC4046 was well tolerated. ClinicalTrials.gov no: NCT02098473.

KW - Esophagus

KW - Immune Response

KW - Placebo-Controlled

KW - Randomized

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