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J Allergy Clin Immunol. 2015 Feb;135(2):500-7. doi: 10.1016/j.jaci.2014.07.049. Epub 2014 Sep 13.

Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis.

Author information

1
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address: Marc.Rothenberg@cchmc.org.
2
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
3
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio; Office of Clinical and Translational Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
4
O & O Alpan LLC, Fairfax, Va.
5
O & O Alpan LLC, Fairfax, Va; Pediatric Gastroenterology of Northern Virginia, Fairfax, Va.
6
Northwestern University Feinberg School of Medicine, Chicago, Ill.
7
Division of Immunology and Allergy, Stanford University Medical Center, Stanford, Calif.
8
Novartis Institutes for Biomedical Research, Basel, Switzerland.
9
Novartis Institutes for Biomedical Research, Cambridge, Mass.
10
Novartis Institutes for Biomedical Research, Horsham, United Kingdom.

Abstract

BACKGROUND:

Eosinophilic esophagitis (EoE) is a chronic allergic disease with limited treatment options.

OBJECTIVE:

We evaluated QAX576, an mAb against IL-13, in the treatment of patients with EoE.

METHODS:

Patients (18-50 years) with proton pump inhibitor-resistant esophageal eosinophilia received intravenous QAX576 (6 mg/kg) or placebo (2:1) at weeks 0, 4, and 8 and were followed for 6 months. The primary end point was the responder rate for a greater than 75% decrease in peak eosinophil counts at week 12. Efficacy was to be declared if the lower 90% confidence limit for the proportion of responders on QAX576 was 35% or greater. Secondary end points included changes in esophageal eosinophil counts, symptoms assessed by questionnaire scores, and quantification of a series of biomarkers.

RESULTS:

Twenty-three patients completed the study up to week 12, and 18 continued to the end of the study. For the proximal and distal esophageal biopsies combined, the responder rate was 12.5% (90% confidence limit, 1% to 43%) with placebo, compared to 40.0% (90% confidence limit, 22% to 61%) with QAX576. Although the primary end point was not met, the mean esophageal eosinophil count decreased by 60% with QAX576 versus an increase of 23% with placebo (P = .004), and the decrease was sustained up to 6 months. There was a trend for improved symptoms, particularly dysphagia. QAX576 improved expression of EoE-relevant esophageal transcripts, including eotaxin-3, periostin, and markers of mast cells and barrier function, for up to 6 months after treatment. QAX576 was well tolerated.

CONCLUSIONS:

QAX576 significantly improved intraepithelial esophageal eosinophil counts and dysregulated esophageal disease-related transcripts in adults with EoE in a sustained manner.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01022970.

KEYWORDS:

IL-13; QAX576; T(H)2 cells; barrier function; cytokine; eosinophilic esophagitis; mAb; mast cell; randomized clinical trial; targeted therapy; transcriptome

PMID:
25226850
DOI:
10.1016/j.jaci.2014.07.049
[Indexed for MEDLINE]

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