Berger W, Gupta N, McAlary M, Fowler-Taylor A. Ann Allergy Asthma Immunol. 2003;91:182–188
Purpose of the Study.
To evaluate safety parameters for 1-year treatment with omalizumab among children 5 to 12 years of age.
A total of 225 patients, 5 to 12 years of age, with a mean duration of asthma of 6.1 years (range: 1–12 years) were studied. All patients had allergic asthma, which had been well controlled for ≥3 months before the study with inhaled corticosteroid doses equivalent to 168 to 420 μg/day beclomethasone dipropionate and rescue albuterol as needed. Ninety percent of the patients were classified as have moderate/severe persistent asthma, and 10% were classified as having severe persistent asthma. The mean total serum immunoglobulin E level was 348 IU/mL (range: 20–1269 IU/mL).
This report included data from a previously published, 28-week study, which was a randomized, double-blind, placebo-controlled, parallel-group trial comparing the addition of omalizumab versus placebo for symptomatic patients receiving beclomethasone dipropionate. The patients who received omalizumab during the double-blind, 28-week study continued to receive open-label omalizumab without interruption for another 24 weeks and were studied with respect to the safety parameters described in this report.
Approximately 93% of patients treated with omalizumab for 52 weeks reported experiencing an adverse event; 85% of those were rated as mild or moderate. This finding was similar to 89% of patients treated with omalizumab and 87% of patients treated with placebo reporting adverse events during the double-blind study. The only statistically significantly greater adverse event among omalizumab-treated patients, compared with placebo-treated patients, in the 28-week study was injury. The higher prevalence of injury among the actively treated patients was not considered to be attributable to treatment and was not associated with adverse events involving the nervous system. The finding was considered to be possibly attributable to increases in activity with improvements in asthma, leading to greater frequencies of injury and trauma among those patients. Among the patients who were treated for 52 weeks with omalizumab, adverse events were numerically greater (by percentage) in all categories, compared with those reported in the 28-week study for either active drug or placebo, but no statistical analysis was reported. The most frequently reported adverse events in the 52-week study were upper respiratory tract infections and headaches. No episodes of anaphylaxis were noted. Urticaria occurred for 11 patients (5%). Urticaria was considered to be possibly treatment-related for 5 patients but was reported to be severe for only 1 of those patients; for that patient, additional treatment with omalizumab was discontinued. Four serious adverse events were reported, but none was considered to be treatment-related. There was no evidence of omalizumab-related decreases in platelet counts among the patients treated for 52 weeks. Antibodies reactive with the antigen-binding fragment of omalizumab were tested for, and no antibodies were detected. Asthma control parameters were not the primary outcome measures in the 52-week extension study, but it was noted that inhaled corticosteroid dose reductions or discontinuation and reductions in asthma exacerbations were maintained at similar levels throughout the 28-week extension period.
Among children 5 to 12 years of age, 52-week treatment with omalizumab was well tolerated. The overall incidence of adverse events was high but was similar to the values reported in the 28-week study for both active drug and placebo. No anaphylactic reactions were reported. Treatment was discontinued for 1 patient because of severe urticaria, which was considered to be possibly treatment-related.
Although the exact role of omalizumab in clinical practice is not entirely clear, these short-term safety data are reassuring.