Omalizumab-induced decrease of FcξRI expression in patients with severe allergic asthma.
BACKGROUND
It is documented that omalizumab treatment reduces the cell surface expression of immunoglobulin E high-affinity receptor (FcɛRI) on several cell types. This has not been investigated in patients with uncontrolled severe persistent allergic asthma.


METHODS
In a double-blind, randomized, placebo-controlled study, patients with severe allergic asthma uncontrolled by high dose inhaled corticosteroids and long-acting β(2)-agonist received either omalizumab (n = 20) or placebo (n = 11) over 16 weeks at appropriate doses and frequencies. Baseline and end of study (week 16) FcɛRI expression on basophils and plasmacytoid dendritic cells was determined by flow cytometry for the primary endpoint. Secondary efficacy endpoints included asthma control and lung function as part of an initial investigation into the use of FcɛRI expression as a marker of response.


RESULTS
In the omalizumab group, and with respect to placebo, FcɛRI expression was significantly reduced at end of study on basophils (-82.6%, p < 0.01) and plasmacytoid dendritic cells (-44.2%, p = 0.029). FcɛRI expression reduction was not found to be correlated with clinical response.


CONCLUSIONS
Long-term omalizumab treatment induced reduction of FcɛRI expression on circulating basophils and plasmacytoid dendritic cells. These changes were not associated with those of clinical features related to severe asthma, which does not support further investigation into its use as a predictive marker of response.


BACKGROUND
The study was registered with ClinicalTrials.gov (identifier: NCT00454051) and the European Clinical Trials Database, EudraCT (identifier: 2006-003591-35).
Chanez
Pascal
P
INSERM U 600, CNRS UMR 6212, Université de la Méditerranée, Marseille, France.
Contin-Bordes
Cécile
C
Garcia
Gilles
G
Verkindre
Christophe
C
Didier
Alain
A
De Blay
Frédéric
F
de Lara
Manuel Tunon
MT
Blanco
Patrick
P
Moreau
Jean-François
JF
Robinson
Philip
P
Bourdeix
Isabelle
I
Trunet
Patrick
P
Le Gros
Vincent
V
Humbert
Marc
M
Molimard
Mathieu
M
D000328:Adult; D000368:Aged; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001491:Basophils / Q000187:drug effects* / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000069444:Omalizumab; D010919:Placebos; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D055815:Young Adult
D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007141:Immunoglobulin Fc Fragments; D010919:Placebos; D000069444:Omalizumab