Humanized Monoclonal Antibody May Be Effective, Safe in Asthma Patients

Laurie Barclay, MD

January 11, 2011

January 11, 2011 — Add-on therapy with subcutaneous omalizumab is safe and effective in patients with moderate to severe allergic asthma, according to the results of a systematic review reported in the January issue of Chest.

"Omalizumab is a humanized monoclonal anti-[immunoglobulin E]IgE for the treatment of severe allergic asthma," write Gustavo J. Rodrigo, MD, from Hospital Central de las Fuerzas Armadas in Montevideo, Uruguay, and colleagues. "Because omalizumab targets an immune system molecule, there has been particular interest in the drug's safety. To establish the efficacy and safety of subcutaneous omalizumab as add-on therapy to corticosteroids, a systematic review of placebo-controlled studies was performed."

Selection criteria for identified trials included randomized, placebo-controlled design; primary outcomes of lowered steroid use and fewer asthma exacerbations; and secondary outcome measures of pulmonary function, use of rescue medication, asthma symptoms, health-related quality of life, and adverse effects.

The investigators identified 8 trials (enrolling a total of 3429 participants) that fulfilled the selection criteria. Compared with patients receiving placebo, those receiving omalizumab were more likely to be able to withdraw from corticosteroids completely at the end of the steroid-reduction phase (relative risk [RR], 1.80; 95% confidence interval [CI], 1.42 - 2.28; P = .00001).

The risk for asthma exacerbations was reduced in patients receiving omalizumab, both at the end of the stable-steroid phase (RR, 0.57; 95% CI, 0.48 - 0.66; P = .0001) and in the adjustable-steroid phase (RR, 0.55; 95% CI, 0.47 - 0.64; P = .0001). Duration of treatment, age, severity of asthma, and risk for bias did not modify this effect, based on post hoc analysis.

Although the omalizumab and placebo groups had similar frequency of serious adverse effects (3.8% vs 5.3%), the omalizumab group had more frequent injection site reactions (19.9% vs 13.2%). The risk for hypersensitivity reactions, cardiovascular effects, or malignant disease did not appear to be increased.

"[I]n 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 review authors write. "The magnitude of the [number needed to treat for benefit] suggests a clinically worthwhile benefit. In addition, asthmatics treated with omalizumab were more likely to be able to withdraw their corticosteroids completely compared with those treated with placebo."

Limitations of the systematic review include identification of only 2 trials that recruited pediatric participants. Of 8 studies included, only 2 reported an appropriate sequence generation, and only 1 study adequately concealed allocation.

"No significant adverse effects were seen among patients taking omalizumab in studies shorter than 1 year," the review authors conclude. "Longer clinical trials will be required for full evaluation of the long-term efficacy and safety of omalizumab."

Some of the study authors have disclosed various financial relationships with Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Merck Sharp & Dome, Schering-Plough, Novartis, and/or Grunenthal.

Chest. 2011;139:28-35. Abstract

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