Safety of anti‐immunoglobulin E therapy with omalizumab in allergic patients at risk of geohelminth infection

A A Cruz,F Lima,E Sarinho,P J Cooper,H Fox,G Ayre,C Martin

doi:10.1111/j.1365-2222.2007.02650.x

Abstract

BackgroundAlthough the role of immunoglobulin E (IgE) in immunity against helminth parasites is unclear, there is concern that therapeutic antibodies that neutralize IgE (anti-IgE) may be unsafe in subjects at risk of helminth infection.ObjectiveWe conducted an exploratory study to investigate the safety of omalizumab (anti-IgE) in subjects with allergic asthma and/or perennial allergic rhinitis at high risk of intestinal helminth infection. The primary safety outcome was risk of infections with intestinal helminths during anti-IgE therapy.MethodsA randomized, double-blind, placebo-controlled trial was conducted in 137 subjects (12–30 years) at high risk of geohelminth infection. All subjects received pre-study anthelmintic treatment, followed by 52 weeks' treatment with omalizumab or placebo.ResultsOf the omalizumab subjects 50% (34/68) experienced at least one intestinal geohelminth infection compared with 41% (28/69) of placebo subjects [odds ratio (OR) 1.47, 95% confidence interval (CI) 0.74–2.95, one-sided P = 0.14; OR (adjusted for study visit, baseline infection status, gender and age) 2.2 (0.94–5.15); one-sided P = 0.035], providing some evidence for a potential increased incidence of geohelminth infection in subjects receiving omalizumab. Omalizumab therapy was well tolerated, and did not appear to be associated with increased morbidity attributable to intestinal helminths as assessed by clinical and laboratory adverse events, maximal helminth infection intensities and additional anthelmintic requirements. Time to first infection (OR 1.30, 95% CI 0.79–2.15, one-sided P = 0.15) was similar between treatment groups. Infection severity and response to anthelmintics appeared to be unaffected by omalizumab therapy.ConclusionsIn this exploratory study of allergic subjects at high risk of helminth infections, omalizumab therapy appeared to be safe and well tolerated, but may be associated with a modest increase in the incidence of geohelminth infection.

Highlights

Intestinal helminth infections caused by Ascaris lumbricoides, hookworm, Trichuris trichiura and StrongyloidesRe-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.stercoralis are the most prevalent helminth parasitic infections in humans, infecting approximately 2 billion people worldwide [1]
ÃBased on positive egg count in faeces sample collected at screening. wSerology for S. stercoralis was performed in a subset of 51 subjects
50% (34/68) of omalizumab subjects experienced at least one intestinal geohelminth infection compared with 41% (28/69) of placebo subjects

Summary

Introduction

Intestinal helminth infections caused by Ascaris lumbricoides, hookworm, Trichuris trichiura and Strongyloides. Stercoralis are the most prevalent helminth parasitic infections in humans, infecting approximately 2 billion people worldwide [1]. Helminth antigens are potent inducers of immunoglobulin E (IgE) production and are capable of stimulating an IgE response in almost all infected individuals [3]. Levels of IgE increase substantially with persistent exposure to helminth parasites, the role of IgE in mediating a protective anti-helminth immune response remains controversial [4]. Animal studies indicate that immune responses to helminths involve multiple effector pathways directed against different stages of the helminth life cycle [5]. Current evidence in humans indicates that protective immunity against intestinal helminths is mediated by type-2 cytokine immune responses [6]. There is little consistent evidence to suggest that antibodies of any particular isotype or subclass represent a primary effector mechanism against these parasites [4]

Methods

Results

Conclusion