Asthma and lower airway disease
Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma

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Background

Many children with asthma continue to experience symptoms despite available therapies.

Objective

This study evaluated the efficacy and safety of omalizumab, a humanized anti-IgE mAb, in children with moderate-to-severe persistent allergic (IgE-mediated) asthma that was inadequately controlled despite treatment with medium-dose or high-dose inhaled corticosteroids (ICSs) with or without other controller medications.

Methods

A randomized, double-blind, placebo-controlled trial enrolled children age 6 to <12 years with perennial allergen sensitivity and history of exacerbations and asthma symptoms despite at least medium-dose ICSs. Patients were randomized 2:1 to receive omalizumab (75-375 mg sc, q2 or q4 wk) or placebo over a period of 52 weeks (24-week fixed-steroid phase followed by a 28-week adjustable-steroid phase).

Results

A total of 627 patients (omalizumab, n = 421; placebo, n = 206) were randomized, with efficacy analyzed in 576 (omalizumab, n = 384; placebo, n = 192). Over the 24-week fixed-steroid phase, omalizumab reduced the rate of clinically significant asthma exacerbations (worsening symptoms requiring doubling of baseline ICS dose and/or systemic steroids) by 31% versus placebo (0.45 vs 0.64; rate ratio, 0.69; P = .007). Over a period of 52 weeks, the exacerbation rate was reduced by 43% versus placebo (P < .001). Omalizumab significantly reduced severe exacerbations. Over a period of 52 weeks, omalizumab had an acceptable safety profile, with no difference in overall incidence of adverse events compared with placebo.

Conclusion

Add-on omalizumab is effective and well tolerated as maintenance therapy in children (6 to <12 years) with moderate-to-severe persistent allergic (IgE-mediated) asthma whose symptoms are inadequately controlled despite medium to high doses of ICSs.

Section snippets

Patients

Patients were boys or girls age 6 to <12 years with moderate-to-severe allergic (IgE-mediated) asthma.27 Patients had inadequately controlled asthma despite receiving at least medium doses of ICS (≥200 μg/d fluticasone propionate via dry powder inhaler or equivalent).27 They had daytime or nighttime symptoms, demonstrated an increase of ≥12% in FEV1 after 4 puffs (4 × 100 μg) or up to 5 mg nebulized albuterol, and had a history of exacerbations (≥2 within 1 year, ≥3 within 2 years, or ≥1 severe

Patient disposition and baseline characteristics

Of the 1443 children screened, 627 children who remained symptomatic during the last 4 weeks of run-in were treated with omalizumab (n = 421) or placebo (n = 206; Fig 1). In the placebo group, 1 additional patient was not randomized and was therefore excluded from the ITT population but included in the safety population (n = 207). The mITT population included 576 patients.

Patient demographic and baseline clinical characteristics were well balanced between treatment groups. The mean age was 8.6

Discussion

This randomized, double-blind, placebo-controlled study in children with moderate-to-severe allergic (IgE-mediated) asthma demonstrates that add-on omalizumab significantly reduces clinically significant asthma exacerbations. The study also demonstrated that omalizumab has an acceptable safety profile and is well tolerated.

Compared with placebo, omalizumab reduced clinically significant exacerbations by 31% during the 24-week fixed-steroid phase. Over the 52-week treatment period, efficacy was

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    Supported by Novartis Pharma AG.

    Disclosure of potential conflict of interest: B. Lanier has served as a consultant for Alcon Laboratories and has received research support from Alcon Laboratories, Genentech/Novartis, and AstraZeneca. T. Bridges has served on the speakers' bureau and has received research support from Novartis and Genentech. The rest of the authors have declared that they have no conflict of interest.

    ClinicalTrials.gov Identifier: NCT00079937

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