Which medications in the drug class Monoclonal Antibodies, Anti-asthmatics are used in the treatment of Pediatric Asthma?

Updated: Jan 08, 2019
  • Author: Girish D Sharma, MD, FCCP, FAAP; Chief Editor: Kenan Haver, MD  more...
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Answer

Monoclonal Antibodies, Anti-asthmatics

Monoclonal antibody effects vary depending on their receptor target. Omalizumab binds to IG-E on the surface of mast cells and basophils. It reduces release of these mediators that promote an allergic response. Mepolizumab and benralizumab inhibit IL-5 binding to eosinophils and results in reduced blood, tissue, and sputum eosinophil levels. Dupilumab inhibits IL-4 receptor alpha, and thereby blocks IL-4 and IL-13 signaling. This in turn reduces cytokine-induced inflammatory response.

Mepolizumab approval was based on 3 key phase 3 trials (DREAM, MENSA, and SIRIUS). Each trial demonstrated statistically significant improvement in decreasing asthma exacerbations and emergency department visits or hospitalization. Mean reduction in glucocorticoid use was 50% in the mepolizumab group, while also reducing the asthma exacerbation rate. Significant improvement in FEV1 was also observed compared with placebo. [71, 72, 73]

Benralizumab approval was based on results from the WINDWARD clinical trial program, including the Phase III exacerbation trials, SIROCCO and CALIMA, and the Phase III oral corticosteroid (OCS)-sparing trial, ZONDA. [74, 75, 76] Results for the 8-week benralizumab dosing regimen from these trials showed significantly reduced annual asthma exacerbation rate (AAER), improved FEV1, and a 75% median reduction in daily OCS use and discontinuation of OCS use in 52% of eligible patients compared with placebo.

Approval for dupilumab was based on the LIBERTY QUEST (n=1902) and VENTURE (n=210) phase 3 clinical trials. In the LIBERTY QUEST trial, patients with moderate-to-severe uncontrolled asthma were administered dupilumab add-on therapy to current maintenance therapy every 2 weeks or matched placebo. Those receiving a 200-mg dose demonstrated a 47.7% lower rate of annualized severe asthma exacerbations compared with placebo add-on (P < 0.001). The 300-mg dose showed a similar response. [82]

In the LIBERTY VENTURE trial, patients with oral corticosteroid-dependent severe asthma were administered dupilumab add-on therapy or matched placebo to current maintenance therapy every 2 weeks for 24 weeks or matched placebo. Corticosteroid doses were gradually decreased from week 4 to week 20 and then maintained for 4 weeks. Patients receiving dupilumab had a 70.1% greater corticosteroid dose reduction compared with 41.9% for placebo add-on (P < 0.001). Additionally, patients receiving dupilumab had a 59% (95% [CI], 37 to 74) lower rate of severe asthma exacerbations than those taking placebo add-on. [83]

Omalizumab (Xolair)

Omalizumab is a recombinant, DNA-derived, humanized IgG monoclonal antibody that binds selectively to human IgE on surface of mast cells and basophils. It reduces mediator release, which promotes allergic response. It is indicated for moderate-to-severe persistent asthma in patients aged 6 years or older who react to perennial allergens in whom symptoms are not controlled by inhaled corticosteroids.

Mepolizumab (Nucala)

Mepolizumab is a humanized IgG1 kappa monoclonal antibody specific for interleukin-5 (IL-5). Mepolizumab binds to IL-5, and therefore stops IL-5 from binding to its receptor on the surface of eosinophils. It is indicated for add-on maintenance treatment of patients with severe asthma aged 6 years or older, and with an eosinophilic phenotype.

Benralizumab (Fasenra)

Benralizumab is a humanized monoclonal antibody (IgG1/kappa-class) selective for the IL-5 alpha subunit of basophils and eosinophils. It is indicated for add-on maintenance treatment of severe asthma in patients aged 12 years or older who have an eosinophilic phenotype.

Dupilumab (Dupixent)

Inhibits IL-4 receptor alpha, and thereby blocks IL-4 and IL-13 signaling. This in turn reduces cytokine-induced inflammatory response. It is indicated as an add-on maintenance treatment for moderate-to-severe asthma in patients aged 12 years or older with eosinophilic phenotype or PO corticosteroid dependent asthma.


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