title: Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis.
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.
authors.affiliation: 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.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Ting
authors.initials: T
authors.lastname: Wen
authors.affiliation: 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.
authors.forename: Allison
authors.initials: A
authors.lastname: Greenberg
authors.affiliation: O & O Alpan LLC, Fairfax, Va.
authors.forename: Oral
authors.initials: O
authors.lastname: Alpan
authors.affiliation: O & O Alpan LLC, Fairfax, Va; Pediatric Gastroenterology of Northern Virginia, Fairfax, Va.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Enav
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Hirano
authors.affiliation: Division of Immunology and Allergy, Stanford University Medical Center, Stanford, Calif.
authors.forename: Kari
authors.initials: K
authors.lastname: Nadeau
authors.affiliation: Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Sergio
authors.initials: S
authors.lastname: Kaiser
authors.affiliation: Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Peters
authors.affiliation: Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Perez
authors.affiliation: Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Ieuan
authors.initials: I
authors.lastname: Jones
authors.affiliation: Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Arm
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, Mass.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Strieter
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, Mass.
authors.forename: Ronald
authors.initials: R
authors.lastname: Sabo
authors.affiliation: Novartis Institutes for Biomedical Research, Horsham, United Kingdom.
authors.forename: Kulasiri A
authors.initials: KA
authors.lastname: Gunawardena
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D016000:Cluster Analysis; D004351:Drug Resistance; D057765:Eosinophilic Esophagitis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D059467:Transcriptome; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D018793:Interleukin-13; D054328:Proton Pump Inhibitors
keywords: IL-13; QAX576; T(H)2 cells; barrier function; cytokine; eosinophilic esophagitis; mAb; mast cell; randomized clinical trial; targeted therapy; transcriptome