What is the role of biological therapy in the treatment of asthma?

From the Guidelines

Biological therapies, such as omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab, are effective treatments for severe asthma that doesn't respond adequately to standard medications, and should be considered after optimizing inhaled corticosteroids, long-acting beta-agonists, and other controller medications. For patients with severe eosinophilic asthma, these monoclonal antibodies are recommended options, typically administered as subcutaneous injections every 2-8 weeks depending on the specific agent 1. Omalizumab targets IgE and is useful for allergic asthma, while mepolizumab, benralizumab, and reslizumab target IL-5 or its receptor to reduce eosinophils. Dupilumab blocks IL-4 and IL-13 signaling, and tezepelumab targets TSLP.

Before starting biological therapy, patients should undergo phenotyping with blood eosinophil counts, IgE levels, FeNO measurements, and allergy testing to determine the most appropriate agent 1. These medications work by interrupting specific inflammatory pathways involved in asthma pathogenesis, reducing exacerbations by 50-70% and allowing steroid dose reduction in many patients. The most recent study 1 supports the use of biological therapies in severe asthma, and highlights the importance of personalized treatment approaches.

Some key points to consider when using biological therapies in asthma include:

• Omalizumab is a potential therapeutic approach for patients with allergic asthma, and has been shown to reduce exacerbations and improve symptoms 1
• Mepolizumab, benralizumab, and reslizumab target IL-5 or its receptor, and are effective in reducing eosinophils and improving asthma control 1
• Dupilumab blocks IL-4 and IL-13 signaling, and has been shown to reduce exacerbations and improve lung function 1
• Tezepelumab targets TSLP, and has been shown to reduce exacerbations and improve asthma control 1

Overall, biological therapies offer a promising treatment option for patients with severe asthma, and should be considered as part of a comprehensive treatment plan.

From the FDA Drug Label

The efficacy of FASENRA for the add-on maintenance treatment of severe asthma, and with an eosinophilic phenotype was evaluated in two randomized, double-blind, parallel-group, placebo-controlled, exacerbation trials, SIROCCO (NCT01928771) and CALIMA (NCT01914757), for 48 and 56 weeks in duration, respectively Studies I and II were 52-week studies in 953 patients with asthma who were required to have a blood eosinophil count of at least 400/mcL (within 3 to 4 weeks of dosing), and at least 1 asthma exacerbation requiring systemic corticosteroid use over the past 12 months

Asthma and Biological Therapy:

• Benralizumab (FASENRA) and Reslizumab (CINQAIR) are two biological therapies used for the treatment of severe asthma with an eosinophilic phenotype.
• These therapies have been evaluated in several clinical trials, including SIROCCO, CALIMA, and Studies I-IV, which demonstrated their efficacy in reducing asthma exacerbations and improving lung function.
• The recommended dosing regimen for Benralizumab (FASENRA) is 30 mg administered every 4 weeks for the first 3 doses, then every 8 weeks thereafter.
• The recommended dosing regimen for Reslizumab (CINQAIR) is 3 mg/kg administered once every 4 weeks.
• Both therapies are used as add-on maintenance treatment for patients with severe asthma who are already receiving inhaled corticosteroids and other controller medications 2, 3, 3.

From the Research

Asthma and Biological Therapy

• Asthma is a heterogeneous disease with considerable variability in disease severity, patterns of airway inflammation, and achievement of disease control on current medications 4.
• Severe asthma affects 5% to 10% of the adult asthma population and is associated with increased morbidity, mortality, and consumption of health care resources 5.
• The advent of biologics is providing a new form of treatment for many with severe asthma, with four mAb biologics approved for clinical use: omalizumab (anti-IgE) and three antieosinophilic interventions (mepolizumab, reslizumab, and benralizumab) 6.

Benefits of Biologics in Asthma Treatment

• Biologics have reduced asthma exacerbations in severe asthma patients 6, 7.
• The antieosinophilic biologics have also improved lung function in severe asthma patients 6, 7.
• The introduction of biologicals has reduced the annualized exacerbation rate significantly, with improvements observed in FEV1 and FeNO following treatment with mepolizumab and benralizumab 7.

Choosing the Right Biologic for Severe Asthma

• The choice of biologics should be based on the available clinical trial data for the desired efficacy outcomes, the biomarker profile of the patient, safety profiles, and opportunities to target two comorbidities with one biologic 8.
• Asthma endotype, clinical biomarkers, and patient-centered factors should be taken into account when choosing a biologic medication for patients with severe asthma 5.
• Biomarkers such as eosinophils, fractional exhaled nitric oxide (FeNO), and immunoglobulin (Ig) E can help identify patients with T2-high inflammation who may benefit from biologic treatment 4.

Safety and Efficacy of Biologics

• The safety profile of biologics has been good, with significant reductions in asthma symptoms, a decreased frequency of exacerbations, and improved lung function in many patients 6, 4.
• However, more data are needed to acquire accurate effect estimates in different subpopulations of patients, and post hoc studies and new comparative studies are needed urgently to test the framework for choosing the right biologic for the right patient 7, 8.