Anti-IgE for chronic asthma.
BACKGROUND
Omalizumab is a recombinant humanised monoclonal antibody directed against immunoglobulin E (IgE) to inhibit the immune system's response to allergen exposure. Omalizumab is directed against the binding site of IgE for its high affinity Fc receptor. It prevents free serum IgE from attaching to mast cells and other effector cells and prevents IgE mediated inflammatory changes. The complexes of Omalizumab and IgE formed as a result of treatment are small and not thought to be able to trigger complement activation or give rise to immune complex mediated pathology.


OBJECTIVE
To determine the efficacy of anti-IgE in patients with allergic asthma.


METHODS
We searched the Cochrane Airways Group Asthma trials register (February 2003) for potentially relevant studies.


METHODS
Randomised control trials examining anti-IgE administered in any manner for any duration.


METHODS
Two reviewers independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature (inhaled, intravenous and subcutaneous injection). Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources.


RESULTS
Eight trials were included in the review, contributing a total of 2037 mild to severe allergic asthmatic participants with high levels of IgE. Treatment with intravenous and subcutaneous Omalizumab resulted in a 98 to 99% reduction in free IgE, reductions which were not observed following placebo treatment. Significant increases in the number of participants who were able to reduce (> 50% reduction in daily corticosteroid usage (four trials): odds ratio (OR) 2.50, 95% confidence interval (CI) 2.02 to 3.10; or completely withdraw their daily steroid intake (four trials): OR 2.50, 95%CI 2.00 to 3.13, were observed. Participants treated with Omalizumab were less likely to suffer an asthma exacerbation (stable steroid phase (three trials): OR 0.46, 95%CI 0.35 to 0.61; steroid reduction phase (three trials) OR 0.46, 95% CI 0.36 to 0.59).


CONCLUSIONS
Omalizumab was significantly more effective than placebo at increasing the numbers of patients who were able to reduce or withdraw their inhaled steroids and was effective in reducing asthma exacerbations. Omalizumab was well tolerated, although the safety profile requires longer term assessment. Patient and physician assessment of the drug was positive. Further assessment in paediatric and severe adult populations is necessary, as is comparison with inhaled corticosteroids.
Walker
S
S
National Respiratory Training Centre, The Athenaeum, 10 Church Street, Warwick, UK, CV34 4AB.
Monteil
M
M
Phelan
K
K
Lasserson
T J
TJ
Walters
E H
EH
D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D002908:Chronic Disease; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D000069444:Omalizumab; D016032:Randomized Controlled Trials as Topic
D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C026408:anti-IgE antibodies; D000069444:Omalizumab; D007073:Immunoglobulin E