What are the indications and guidelines for biologics, including Omalizumab (anti-IgE antibody), Mepolizumab (interleukin-5 inhibitor), Reslizumab (interleukin-5 inhibitor), and Benralizumab (anti-interleukin-5 receptor alpha antibody), in the treatment of severe asthma?

Biologics for Severe Asthma: Indications and Guidelines

Biologics should be considered for patients with severe persistent asthma (steps 5 and 6) who remain uncontrolled despite high-dose ICS plus LABA therapy, particularly those with specific biomarker profiles indicating T2 inflammation. 1

Available Biologics and Their Mechanisms

Omalizumab (Anti-IgE)

• Indication: Patients ≥12 years with moderate to severe persistent allergic asthma whose symptoms are inadequately controlled with ICS
• Specific Requirements:
  • Positive skin test or in vitro reactivity to perennial aeroallergen
  • IgE-mediated allergic asthma (elevated IgE levels)
  • Used at steps 5-6 of asthma management 1
• Mechanism: Binds to free IgE, blocking the allergic cascade by preventing IgE from binding to effector cells (mast cells, basophils) 1

Mepolizumab (Anti-IL-5)

• Indication: Maintenance treatment of severe asthma in patients with an eosinophilic phenotype 2
• Specific Requirements:
  • Elevated blood eosinophil counts
  • Used at steps 5-6 of asthma management
• Mechanism: Targets IL-5 directly, reducing eosinophil production and survival 3

Reslizumab (Anti-IL-5)

• Indication: Add-on maintenance treatment for severe eosinophilic asthma
• Specific Requirements:
  • Elevated blood eosinophil counts
  • Only biologic administered intravenously 3
• Mechanism: Targets IL-5 directly, similar to mepolizumab 3

Benralizumab (Anti-IL-5Rα)

• Indication: Add-on maintenance treatment for severe eosinophilic asthma
• Specific Requirements:
  • Elevated blood eosinophil counts
  • Used at steps 5-6 of asthma management
• Mechanism: Targets IL-5 receptor alpha, causing rapid and nearly complete depletion of eosinophils 3

Patient Selection Algorithm

Step 1: Confirm Severe Persistent Asthma

• Patient must be on high-dose ICS plus LABA therapy (steps 5-6)
• Symptoms remain uncontrolled despite optimal therapy
• Verify adherence, inhaler technique, and environmental control measures 1

Step 2: Biomarker Assessment

• Blood eosinophil count:
  • ≥300 cells/μL: Consider anti-IL-5 therapy (mepolizumab, reslizumab) or anti-IL-5Rα (benralizumab) 4
• IgE levels and allergen sensitization:
  • Elevated IgE + positive allergen testing: Consider omalizumab 1
• FeNO measurement:
  • Elevated FeNO: Additional indicator of T2 inflammation 1

Step 3: Consider Comorbidities

• Nasal polyps: May respond better to anti-IL-5 therapies or dupilumab 3
• Atopic dermatitis: Consider therapies that target multiple atopic conditions 3
• Eosinophilic granulomatosis with polyangiitis (EGPA): Mepolizumab has specific indication 2

Efficacy Outcomes

All biologics demonstrate significant efficacy in reducing exacerbations in severe asthma:

• Benralizumab: 47% reduction (IRR 0.53,95% CI 0.39-0.72)
• Mepolizumab: 51% reduction (IRR 0.49,95% CI 0.38-0.66)
• Reslizumab: 54% reduction (IRR 0.46,95% CI 0.37-0.58)
• Omalizumab: 44% reduction (IRR 0.56,95% CI 0.40-0.77) 4

Oral Corticosteroid-Sparing Effects

• Benralizumab, mepolizumab, and dupilumab have demonstrated high-certainty evidence for reducing oral corticosteroid requirements 4
• This is particularly important for patients dependent on oral corticosteroids for asthma control

Clinical Pearls and Pitfalls

Pearls:

• Assess for specific biomarkers before initiating biologic therapy
• Allow 3-4 months to evaluate response to biologic therapy
• Consider comorbidities when selecting a biologic agent
• All approved biologics have excellent safety profiles 3

Pitfalls:

• Biologics are not indicated for acute asthma symptoms or exacerbations 2
• Failure to check adherence to conventional therapy before initiating biologics
• Not monitoring for parasitic infections before and during anti-IL-5 therapy 2
• Inadequate assessment of biomarkers leading to selection of inappropriate biologic

Special Considerations

Pediatric Use

• Omalizumab is approved for children as young as 6 years old 1
• Limited data exists for other biologics in pediatric populations 4

Pregnancy

• Assess risk-benefit ratio carefully
• Uncontrolled asthma poses greater risk than medications during pregnancy 5

Switching Biologics

• Consider switching biologics after 3-6 months if inadequate response
• When switching, select a biologic with a different mechanism of action 6

In rare cases of multi-pathway T2 inflammation not responding to a single biologic, combination therapy with two biologics may be considered, though this approach requires further study and is not yet part of standard guidelines 7.