Treatment of chronic autoimmune urticaria with omalizumab.
BACKGROUND
Approximately 45% of patients with chronic urticaria have an IgG autoantibody directed to the alpha-subunit of the high-affinity IgE receptor (chronic autoimmune urticaria, CAU) leading to cutaneous mast cell and basophil activation. Treatment of allergic asthma with omalizumab produces rapid reduction in free IgE levels and subsequent decrease in Fc epsilon RI expression on mast cells and basophils. If this occurs in CAU, cross-linking of IgE receptors by autoantibody would be less likely, reducing cell activation and urticaria/angioedema.


OBJECTIVE
To investigate the efficacy of omalizumab in patients with CAU symptomatic despite antihistamine therapy.


METHODS
Twelve patients with CAU, identified by basophil histamine release assay and autologous skin test, with persistent symptoms for at least 6 weeks despite antihistamines, were treated with placebo for 4 weeks followed by omalizumab (>or=0.016 mg/kg/IU mL(-1) IgE per month) every 2 or 4 weeks for 16 weeks. Primary efficacy variable was change from baseline to the final 4 weeks of omalizumab treatment in mean Urticaria Activity Score (UAS, 0-9 scale). Changes in rescue medication use and quality of life were assessed.


RESULTS
Mean UAS declined significantly from baseline to the final 4 weeks of omalizumab treatment (7.50 +/- 1.78 to 2.66 +/- 3.31, -4.84 +/- 2.86, P = .0002). Seven patients achieved complete symptom resolution. In 4 patients, mean UAS decreased, but urticaria persisted. One patient did not respond. Rescue medication use was reduced significantly, and quality of life improved. No adverse effects were reported or observed.


CONCLUSIONS
This exploratory proof of concept study suggests omalizumab is an effective therapy for CAU resistant to antihistamines.
Kaplan
Allen P
AP
National Allergy, Asthma, and Urticaria Centers of Charleston, Charleston, SC, USA. kaplana@musc.edu
Joseph
Kusumam
K
Maykut
Robert J
RJ
Geba
Gregory P
GP
Zeldin
Robert K
RK
D000328:Adult; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006919:Hydroxyzine / Q000627:therapeutic use; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D000069444:Omalizumab; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism; D014581:Urticaria / Q000188:drug therapy* / Q000276:immunology
D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001323:Autoantibodies; D006634:Histamine H1 Antagonists; D017455:Receptors, IgE; D000069444:Omalizumab; D006919:Hydroxyzine; D007073:Immunoglobulin E