What is the efficacy of biologics in severe asthma?

From the Guidelines

Biologics have shown significant efficacy in treating severe asthma, particularly for patients who remain symptomatic despite high-dose inhaled corticosteroids and long-acting beta-agonists. The most commonly used biologics include anti-IgE (omalizumab), anti-IL-5 (mepolizumab, reslizumab), anti-IL-5R (benralizumab), and anti-IL-4R (dupilumab) 1.

Key Points

• Omalizumab is effective for allergic asthma, reducing exacerbations by 25-60% and improving quality of life.
• For eosinophilic asthma, anti-IL-5 therapies like mepolizumab (100mg subcutaneously every 4 weeks) and reslizumab (3mg/kg IV every 4 weeks) reduce exacerbations by 50-70% and allow steroid dose reduction.
• Benralizumab (30mg subcutaneously every 8 weeks after initial monthly doses) works rapidly by depleting eosinophils and can reduce exacerbations by up to 70%.
• Dupilumab (200-300mg subcutaneously every 2 weeks) targets both type 2 inflammation pathways and shows 50-70% reduction in exacerbations while improving lung function.
• Patient selection is crucial - biomarkers like blood eosinophil counts, FeNO levels, and specific IgE help determine which biologic will be most effective for individual patients.

Mechanism of Action

These medications work by targeting specific inflammatory pathways involved in severe asthma, blocking the action of key mediators that drive airway inflammation, remodeling, and hyperresponsiveness.

Administration and Monitoring

It is essential to monitor patients for potential adverse effects, such as anaphylaxis with omalizumab, and to educate patients about the risks and appropriate treatment if it occurs 1.

Clinical Considerations

The use of biologics in severe asthma should be considered in the context of the patient's overall clinical profile, including their symptoms, lung function, and biomarker profiles. A thorough evaluation of the patient's response to treatment and regular monitoring of their condition are crucial to optimize treatment outcomes.

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 SIROCCO and CALIMA were randomized, double-blind, parallel-group, placebo-controlled, exacerbation trials in patients 12 years of age and older and 48 and 56 weeks in duration, respectively. FASENRA administered once every 4 weeks for the first 3 doses, and then every 4 or 8 weeks thereafter as add-on to background treatment was evaluated compared to placebo.

The efficacy of biologics, specifically benralizumab (FASENRA), in severe asthma is supported by two randomized, double-blind, parallel-group, placebo-controlled, exacerbation trials, SIROCCO and CALIMA.

• The trials demonstrated the efficacy of FASENRA as an add-on maintenance treatment for severe asthma with an eosinophilic phenotype.
• The recommended dosing regimen is 30 mg FASENRA administered every 4 weeks for the first 3 doses, then every 8 weeks thereafter. The exact efficacy of biologics in severe asthma cannot be directly stated from the provided information, but it is supported by the results of the SIROCCO and CALIMA trials 2.

From the Research

Efficacy of Biologics in Severe Asthma

• Biologics have been shown to reduce exacerbation rates in severe asthma, with high certainty of evidence for benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab 3.
• These biologics have also been found to reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence for benralizumab, dupilumab, and mepolizumab 3.
• Improvements in asthma control, quality of life (QoL), and forced expiratory volume in 1 second (FEV1) have been observed with moderate certainty of evidence for all evaluated biologics 3, 4.

Reduction in Exacerbations and Oral Corticosteroids

• The incidence rate ratio (IRR) for exacerbations was found to be:
  • 0.53 (95% CI 0.39 to 0.72) for benralizumab 3
  • 0.43 (95% CI 0.32 to 0.59) for dupilumab 3
  • 0.49 (95% CI 0.38 to 0.66) for mepolizumab 3
  • 0.56 (95% CI 0.40 to 0.77) for omalizumab 3
  • 0.46 (95% CI 0.37 to 0.58) for reslizumab 3
• A 54% reduction in maintenance OCS dose was observed in patients receiving biologic therapy 5.

Real-World Effectiveness and Predictors of Response

• Real-world studies have confirmed the effectiveness of asthma biologics in reducing exacerbations, improving asthma control, and lung function 5.
• Predictors of response to biologics include nonsmoking status, higher baseline FEV1, gastroesophageal reflux disease, and eosinophil counts greater than 500 cells/μL 5.
• Switching biologics can still result in significant improvements in exacerbation frequency, maintenance OCS dose, and asthma control for patients who have a suboptimal response to one biologic 5.