Monoclonal Antibodies in Asthma
Key Points
- Biological agents targeting specific inflammatory pathways
- Used in severe/refractory asthma
- Require phenotyping and endotyping of asthma
- Significant reduction in exacerbations
- Steroid-sparing effect
Classification by Target
- Anti-IgE: Omalizumab
- Anti-IL5: Mepolizumab, Reslizumab
- Anti-IL5R: Benralizumab
- Anti-IL4R: Dupilumab
- Anti-TSLP: Tezepelumab
Specific Monoclonal Antibodies
Omalizumab (Anti-IgE)
- Mechanism: Binds free IgE, prevents IgE-receptor interaction
- Indications:
- Age ≥6 years with moderate-severe allergic asthma
- Elevated serum IgE (30-1500 IU/mL)
- Positive aeroallergen testing
- Dosing:
- Based on weight and serum IgE levels
- 150-375 mg SC q2-4 weeks
Mepolizumab (Anti-IL5)
- Mechanism: Blocks IL-5, reduces eosinophil production/survival
- Indications:
- Age ≥6 years with severe eosinophilic asthma
- Blood eosinophils ≥150 cells/μL
- Dosing:
- 6-11 years: 40 mg SC q4 weeks
- ≥12 years: 100 mg SC q4 weeks
Dupilumab (Anti-IL4R)
- Mechanism: Blocks IL-4/IL-13 signaling
- Indications:
- Age ≥6 years with moderate-severe eosinophilic/Type 2 asthma
- Oral corticosteroid-dependent asthma
- Dosing:
- 6-11 years: 100-200 mg SC q2 weeks
- ≥12 years: 200-300 mg SC q2 weeks
Benralizumab (Anti-IL5R)
- Mechanism: Targets IL-5 receptor, induces eosinophil apoptosis
- Indications:
- Age ≥12 years with severe eosinophilic asthma
- Blood eosinophils ≥300 cells/μL
- Dosing: 30 mg SC q4-8 weeks
Clinical Applications
Patient Selection
- Biomarker Assessment:
- Blood eosinophils
- Serum IgE
- FeNO levels
- Allergen-specific IgE
- Clinical Characteristics:
- Exacerbation history
- Steroid dependency
- Comorbidities
- Asthma phenotype
Treatment Goals
- Reduction in exacerbations
- Improved symptom control
- Steroid dose reduction
- Enhanced quality of life
- Prevention of lung function decline
Administration and Monitoring
Pre-Treatment Assessment
- Baseline Laboratory Tests:
- Complete blood count with differential
- Serum IgE levels
- Allergen-specific IgE/skin testing
- FeNO measurement
- Clinical Assessment:
- Asthma control status
- Exacerbation history
- Current medications
- Comorbidity evaluation
Monitoring Parameters
- Efficacy Measures:
- Exacerbation frequency
- Symptom scores
- Lung function tests
- Medication requirements
- Safety Monitoring:
- Injection site reactions
- Hypersensitivity reactions
- Blood eosinophil levels
- Helminth infections
Clinical Considerations
Adverse Effects
- Common:
- Injection site reactions
- Headache
- Nasopharyngitis
- Upper respiratory infections
- Serious:
- Anaphylaxis (rare)
- Parasitic infections
- Herpes zoster reactivation
Special Populations
- Pregnancy: Limited data available
- Immunocompromised: Increased infection risk
- Parasitic infections: Treat before initiation
Cost Considerations
- High medication costs
- Insurance coverage verification
- Prior authorization requirements
- Patient assistance programs
Treatment Duration
- Initial evaluation at 4-6 months
- Continue if clear benefit shown
- Annual reassessment of need
- Consider step-down in well-controlled patients
Further Reading
