Chest

Chest

Volume 139, Issue 1, January 2011, Pages 28-35
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Original Research
Asthma
Efficacy and Safety of Subcutaneous Omalizumab vs Placebo as Add-on Therapy to Corticosteroids for Children and Adults With Asthma: A Systematic Review

https://doi.org/10.1378/chest.10-1194Get rights and content

Background

Omalizumab is a humanized monoclonal anti-IgE for the treatment of severe allergic asthma. Because omalizumab targets an immune system molecule, there has been particular interest in the drug's safety.

Methods

To establish the efficacy and safety of subcutaneous omalizumab as add-on therapy to corticosteroids, a systematic review of placebo-controlled studies was performed. Primary outcomes were reduction of steroid use and asthma exacerbations. Secondary outcome measures included lung function, rescue medication use, asthma symptoms, health-related quality of life, and adverse effects.

Results

Eight trials (3,429 participants) fulfilled the selection criteria. At the end of the steroid-reduction phase, patients taking omalizumab were more likely to be able to withdraw from corticosteroids completely compared with those taking placebo (relative risk [RR] = 1.80; 95% CI, 1.42-2.28; P = .00001). Omalizumab patients showed a decreased risk of asthma exacerbations at the end of the stable (RR = 0.57; 95% CI, 0.48-0.66; P = .0001) and adjustable-steroid phases (RR = 0.55; 95% CI, 0.47-0.64; P = .0001); post-hoc analysis suggests this effect was independent of duration of treatment, age, severity of asthma, and risk of bias. The frequency of serious adverse effects was similar in the omalizumab (3.8%) and placebo (5.3%) groups. However, injection site reactions were more frequent in the omalizumab patients (19.9% vs 13.2%). There were no indications of increased risk of hypersensitivity reactions, cardiovascular effects, or malignant neoplasms.

Conclusions

Data indicate that the efficacy of add-on omalizumab in patients with moderate-to-severe allergic asthma is accompanied by an acceptable safety profile.

Section snippets

Search and Selection Criteria

We identified studies from MEDLINE, EMBASE (January 1980-April 2010), and Cochrane Controlled Trials Register (CENTRAL) (first quarter 2010) databases using the following medical subject headings, full text, and keywords: “anti-IgE” or “anti-immunoglobulin E” or “anti-IgE antibody” or “omalizumab” or “rhuMAb-E25” or “Xolair” and “asthma.” Also, we performed a search of relevant files from the Novartis (http://www.novartisclinicaltrials.com) and FDA (www.fda.gov) databases. Trials published

Results

Eight studies11, 12, 23, 24, 25, 26, 27, 28 met the inclusion criteria and were selected for analysis (a total of 3,429 patients, 1,883 receiving omalizumab and 1,546 placebo) (Fig 1). Cumulative exposure (patient-years) was 1,080 for omalizumab and 823 for placebo. The mean baseline IgE serum level was 273 IU/mL (range 179-470 IU/mL). Omalizumab was given in all studies at doses of 0.016 mg/kg/international units/mL every 2 to 4 weeks (Table 1). After a run-in phase, omalizumab was

Discussion

This is a more extensive systematic review performed exclusively to explore the efficacy and safety of subcutaneous omalizumab as add-on therapy to corticosteroids in schoolchildren, adolescents, and adults with moderate to severe persistent allergic asthma. Asthmatics treated with omalizumab during a steroid-reduction phase increased the likelihood of greater steroid reduction. Thus, omalizumab-treated patients were more likely to be able to withdraw their corticosteroids completely or to

Conclusions

In conclusion, this meta-analysis shows that in school-aged children, adolescents, and adults with moderate-to-severe persistent allergic asthma, subcutaneous injection of omalizumab (0.016 mg/kg/international units/mL every 2 to 4 weeks depending on body weight) was superior to placebo in preventing asthma exacerbation at the end of the stable-steroid phase and in the adjustable-steroid phase. The magnitude of the NNTBs suggests a clinically worthwhile benefit.

In addition, asthmatics treated

Acknowledgments

Author contributions: Dr Rodrigo: contributed to the study concept and design, and the acquisition, analysis, and interpretation of data; drafting of the submitted article and critical revision for important intellectual content; and final approval of the version to be published.

Dr Neffen: contributed to the study concept and design and interpretation of data; critical revision of the article for important intellectual content; and final approval of the version to be published.

Dr

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