What is the role of biologic agents in the treatment of asthma?

Updated: Oct 07, 2019
  • Author: John J Oppenheimer, MD; Chief Editor: Michael A Kaliner, MD  more...
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Omalizumab (Xolair) was approved by the FDA in 2003 for use in adults and adolescents (≥12 years) with persistent, moderate to severe asthma who have a positive skin-test result or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids. In 2016, its indication was expanded to include patients 6 years of age and older. It is generally used for patients with elevated serum IgE levels and evidence of perennial allergy. However, more recent studies suggest that there may be other biomarkers that predict therapeutic response (add Hanania reference). Omalizumab is given by subcutaneous injection every 2–4 weeks based on initial serum IgE level and body weight.

Omalizumab is a humanized murine IgG antibody against the Fc component of the IgE antibody (the part that attaches to mast cell surfaces). Use of this antibody prevents IgE from binding directly to the mast cell receptor, thereby preventing cell degranulation without causing degranulation itself.

Multiple phase 3 trials show that, compared with placebo injections, treatment is associated with larger median inhaled steroid dose reduction (83% vs 50%), a higher percentage of discontinuation of inhaled steroids (42% vs 19%), and fewer asthma exacerbations (approximately 15% vs 30%). Quality of life and the use of rescue inhalers and emergency departments may also be improved. Omalizumab has been shown to reduce the number of asthma exacerbations. Studies have shown that omalizumab decreases steroid burden while increasing lung function and quality of life when combined with inhaled corticosteroid treatment in patients younger than 12 years with moderate-to-severe asthma. [44, 45]

Prescribers must be prepared and equipped to recognize and treat anaphylaxis should it occur (0.1% in studies and 0.2% in postmarketing surveillance). Guidelines are evolving, but recommendations advise observation of patients for 2 hours after the first 2 injections and then for 30 minutes for injections thereafter. Reactions have been reported 4 days later. Patients must carry self-injectable epinephrine kits.

Other adverse effects are rare and include upper respiratory infection symptoms, headache, and urticaria (2%) without anaphylaxis. Transient thrombocytopenia has also been noted but not in humans.

Antibodies are formed against the anti-IgE antibody, but these do not appear to cause immune-complex deposition or other significant problems. To date, decreased IgE levels have not been shown to inhibit a patient’s ability to fight infection (including parasites). Registration trials raised a question of increased risk of malignancy, but this has not been seen in the postmarketing data.

The EXCELS trial (Evaluating the Clinical Effectiveness and Long-Term Safety in Patients with Moderate to Severe Asthma) led to the addition of warnings related to potential cardiovascular risks. [46]

Newer biologic agents have entered the market in recent years. These include anti-eosinophilic agents (mepolizumab, reslizumab, and benralizumab). In patients with an eosinophilic subtype, addition of these agents has been shown to reduce severe asthma exacerbations. The newest biologic to be approved for asthma is dupilumab, which works by blocking IL-4 and IL-13 pathways. These agents have shown efficacy in patients with severe refractory asthma, with a favorable side effect profile.

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