Individually dosed omalizumab facilitates peanut oral immunotherapy in peanut allergic adolescents

Clin Exp Allergy. 2019 Oct;49(10):1328-1341. doi: 10.1111/cea.13469. Epub 2019 Aug 15.

Abstract

Background: Peanut oral immunotherapy (pOIT) has showed good short-term outcomes, but allergic reactions may prevent effective up-dosing and is a major cause of stopping OIT. In placebo-controlled trials, omalizumab has been shown to facilitate allergen immunotherapy and increase tolerance to peanut.

Objective: We hypothesized that by combining omalizumab with pOIT, and monitor treatment effects with basophil allergen threshold sensitivity tests (CD-sens), peanut allergic patients could safely initiate pOIT and thereafter slowly withdraw omalizumab.

Methods: This is the 2nd part of a one-armed open phase-2 study where peanut allergic adolescents (n = 23) started pOIT after an individualized omalizumab treatment. The pOIT dose was increased from 280 to 2800 mg peanut protein in 8 weeks followed by an individualized step-wise withdrawal of omalizumab, based on clinical symptoms and CD-sens levels. pOIT continued for 12 weeks followed by an open peanut challenge. Peanut CD-sens and allergen-binding activity (ABA) and IgE-ab, IgG-ab and IgG4-ab to peanut and its components were measured during the study.

Results: All 23 patients successfully reached the 2800 mg maintenance dose. Moderate/systemic allergic reactions were rare while receiving full-dose omalizumab. Eleven of 23 (48%) successfully continued with pOIT after omalizumab was stopped. Compared to treatment failures, median baseline IgE-ab to peanut components Ara h 1-3 and CD-sens to peanut were significantly lower among successfully treated patients and IgG4-ab to peanut, Ara h 2 and 6 increased significantly more during treatment.

Conclusions and clinical relevance: This study indicates that omalizumab is an effective adjunctive therapy for initiation and rapid up-dosing of pOIT; however, adverse events from pOIT become more frequent as omalizumab doses are decreased.

Clinical trials registration: ClinicalTrials.gov; NCT02402231. EudraCT; 2012-005625-78.

Keywords: anaphylaxis; basophil; food allergy; omalizumab; oral immunotherapy; paediatrics.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Desensitization, Immunologic*
  • Female
  • Humans
  • Immunoglobulin E / immunology
  • Immunoglobulin G / immunology
  • Male
  • Omalizumab / administration & dosage*
  • Peanut Hypersensitivity* / immunology
  • Peanut Hypersensitivity* / pathology
  • Peanut Hypersensitivity* / therapy
  • Precision Medicine*

Substances

  • Immunoglobulin G
  • Omalizumab
  • Immunoglobulin E

Associated data

  • ClinicalTrials.gov/NCT02402231
  • EudraCT/2012‐005625‐78