title: Extracorporeal IgE Immunoadsorption in Allergic Asthma: Safety and Efficacy.
abstract: 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.
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Lupinek
authors.affiliation: Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Derfler
authors.affiliation: Clinical Division of Respiratory Medicine, Department of Internal Medicine II, Medical University of Vienna, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lee
authors.affiliation: Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Prikoszovich
authors.affiliation: Clinical Division of Respiratory Medicine, Department of Internal Medicine II, Medical University of Vienna, Austria.
authors.forename: Oliver
authors.initials: O
authors.lastname: Movadat
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Wollmann
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria.
authors.forename: Carolin
authors.initials: C
authors.lastname: Cornelius
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria.
authors.forename: Milena
authors.initials: M
authors.lastname: Weber
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Austria.
authors.forename: Renate
authors.initials: R
authors.lastname: Fröschl
authors.affiliation: Department of Otorhinolaryngology, Medical University of Vienna, Austria.
authors.forename: Regina
authors.initials: R
authors.lastname: Selb
authors.affiliation: Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Blatt
authors.affiliation: Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Dubravka
authors.initials: D
authors.lastname: Smiljkovic
authors.affiliation: Fresenius Medical Care Deutschland GmbH, Clinical Research, Bad Homburg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Schoder
authors.affiliation: Fresenius Medical Care Adsorber Tec GmbH, Krems, Austria.
authors.forename: René
authors.initials: R
authors.lastname: Cervenka
authors.affiliation: Fresenius Medical Care Adsorber Tec GmbH, Krems, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Plaichner
authors.affiliation: Biomay AG, Vienna, Austria.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Stegfellner
authors.affiliation: Biomay AG, Vienna, Austria.
authors.forename: Hans
authors.initials: H
authors.lastname: Huber
authors.affiliation: Biomay AG, Vienna, Austria.
authors.forename: Rainer
authors.initials: R
authors.lastname: Henning
authors.affiliation: Fresenius Medical Care Deutschland GmbH, Clinical Research, Bad Homburg, Germany.
authors.forename: Justyna
authors.initials: J
authors.lastname: Kozik-Jaromin
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Perkmann
authors.affiliation: Department of Otorhinolaryngology, Medical University of Vienna, Austria.
authors.forename: Verena
authors.initials: V
authors.lastname: Niederberger
authors.affiliation: Clinical Division of Respiratory Medicine, Department of Internal Medicine II, Medical University of Vienna, Austria.
authors.forename: Ventzislav
authors.initials: V
authors.lastname: Petkov
authors.affiliation: Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.affiliation: Fresenius Medical Care Deutschland GmbH, Clinical Research, Bad Homburg, Germany.
authors.forename: Adelheid
authors.initials: A
authors.lastname: Gauly
authors.affiliation: Fresenius Medical Care Adsorber Tec GmbH, Krems, Austria.
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Leinenbach
authors.affiliation: Fresenius Medical Care Deutschland GmbH, Clinical Research, Bad Homburg, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Uhlenbusch-Koerwer
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria. Electronic address: rudolf.valenta@meduniwien.ac.at.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
mesh_terms: D000293:Adolescent; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000276:immunology; D001249:Asthma / Q000097:blood / Q000628:therapy*; D001781:Blood Component Removal / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology; D007163:Immunosorbent Techniques / Q000009:adverse effects* / Q000295:instrumentation; D008297:Male; D008875:Middle Aged; D000069444:Omalizumab / Q000276:immunology
chemical_list: D018927:Anti-Asthmatic Agents; D000069444:Omalizumab; D007073:Immunoglobulin E
keywords: Allergy; Asthma; IgE; IgEnio; Immunoadsorption