EBioMedicine (Mar 2017)

Extracorporeal IgE Immunoadsorption in Allergic Asthma: Safety and Efficacy

  • Christian Lupinek,
  • Kurt Derfler,
  • Silvia Lee,
  • Thomas Prikoszovich,
  • Oliver Movadat,
  • Eva Wollmann,
  • Carolin Cornelius,
  • Milena Weber,
  • Renate Fröschl,
  • Regina Selb,
  • Katharina Blatt,
  • Dubravka Smiljkovic,
  • Volker Schoder,
  • René Cervenka,
  • Thomas Plaichner,
  • Gottfried Stegfellner,
  • Hans Huber,
  • Rainer Henning,
  • Justyna Kozik-Jaromin,
  • Thomas Perkmann,
  • Verena Niederberger,
  • Ventzislav Petkov,
  • Peter Valent,
  • Adelheid Gauly,
  • Hans Peter Leinenbach,
  • Ingrid Uhlenbusch-Koerwer,
  • Rudolf Valenta

DOI
https://doi.org/10.1016/j.ebiom.2017.02.007
Journal volume & issue
Vol. 17, no. C
pp. 119 – 133

Abstract

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Background: Prevention of IgE-binding to cellular IgE-receptors by anti-IgE (Omalizumab) is clinically effective in allergic asthma, but limited by IgE threshold-levels. To overcome this limitation, we developed a single-use IgE immunoadsorber column (IgEnio). IgEnio is based on a recombinant, IgE-specific antibody fragment and can be used for the specific extracorporeal desorption of IgE. Objective: To study safety and efficacy of IgEnio regarding the selective depletion of IgE in a randomized, open-label, controlled pilot trial in patients with allergic asthma and to investigate if IgEnio can bind IgE-Omalizumab immune complexes. Methods: Fifteen subjects were enrolled and randomly assigned to the treatment group (n = 10) or to the control group (n = 5). Immunoadsorption was done by veno-venous approach, processing the twofold calculated plasma volume during each treatment. A minimum average IgE-depletion of 50% after the last cycle in the intention-to-treat population was defined as primary endpoint. Safety of the treatment was studied as secondary endpoint. In addition, possible changes in allergen-specific sensitivity were investigated, as well as clinical effects by peak flow measurement and symptom-recording. The depletion of IgE-Omalizumab immune complexes was studied in vitro. The study was registered at clinicaltrials.gov (NCT02096237) and conducted from December 2013 to July 2014. Results: IgE immunoadsorption with IgEnio selectively depleted 86.2% (±5.1% SD) of IgE until the end of the last cycle (p < 0.0001). Removal of pollen allergen-specific IgE was associated with a reduction of allergen-specific basophil-sensitivity and prevented increases of allergen-specific skin-sensitivity and clinical symptoms during pollen seasons. IgEnio also depleted IgE-Omalizumab immune complexes in vitro. The therapy under investigation was safe and well-tolerated. During a total of 81 aphereses, 2 severe adverse events (SAE) were recorded, one of which, an episode of acute dyspnea, possibly was related to the treatment and resolved after administration of antihistamines and corticosteroids. Conclusions: This pilot study indicates that IgE immunoadsorption with IgEnio may be used to treat patients with pollen-induced allergic asthma. Furthermore, the treatment could render allergic patients with highly elevated IgE-levels eligible for the administration of Omalizumab and facilitate the desorption of IgE-Omalizumab complexes. This study was funded by Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany.

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