Treatment of Eosinophilic Asthma
Foundation: Optimize Inhaled Corticosteroid and Long-Acting Beta-Agonist Therapy First
Before escalating to biologic therapies, patients with severe eosinophilic asthma must be on high-dose inhaled corticosteroids combined with long-acting beta-agonists (ICS/LABA), as this combination remains the cornerstone of treatment and is required before considering anti-IL-5 medications. 1, 2
Initial Controller Therapy Algorithm
- Start with high-dose ICS/LABA combination therapy for severe persistent asthma, as this provides superior symptom control and exacerbation reduction compared to ICS alone 1
- Verify proper inhaler technique and medication adherence before concluding treatment failure, as these are the most common reasons for apparent uncontrolled asthma 2
- Never use LABA as monotherapy due to increased risk of asthma-related deaths; it must always be combined with ICS 2
Third-Line Add-On Options Before Biologics
- Consider adding a long-acting muscarinic antagonist (LAMA) such as umeclidinium 62.5 mcg once daily to existing ICS/LABA for patients ≥12 years with uncontrolled asthma and FEV1 <80% predicted 2
- Leukotriene modifiers (montelukast 10 mg daily) can be added to high-dose ICS/LABA as a reasonable option before escalating to biologics, particularly in patients with aspirin-exacerbated respiratory disease 3, 2
Anti-IL-5 Biologic Therapy: When and Which Agent
Indications for Anti-IL-5 Therapy
Add anti-IL-5 biologics when patients remain uncontrolled on high-dose ICS/LABA despite optimized inhaler technique and adherence, particularly when blood eosinophils are elevated (≥200-300 cells/mcL). 4, 5
- Anti-IL-5 medications reduce asthma exacerbations by approximately 50% and allow for oral corticosteroid dose reduction in severe eosinophilic asthma 5, 6
- These agents work by blocking IL-5, the major cytokine responsible for eosinophil growth, differentiation, recruitment, activation, and survival 4
- Blood eosinophil reduction occurs within 4 weeks of treatment initiation and is maintained throughout therapy 4
Choosing Between Anti-IL-5 Agents
All three available anti-IL-5 biologics (mepolizumab, reslizumab, benralizumab) demonstrate similar efficacy in reducing exacerbations and improving asthma control, with no head-to-head studies showing superiority of one agent over another. 5, 6, 7
Mepolizumab (Subcutaneous)
- Dosing: 100 mg subcutaneously every 4 weeks for adults and adolescents with severe eosinophilic asthma 4
- Mechanism: Binds directly to IL-5, preventing it from binding to the IL-5 receptor on eosinophils 4
- Efficacy: Reduces blood eosinophils to a geometric mean of 40 cells/mcL (84% reduction) within 4 weeks 4
- Advantages: Subcutaneous administration allows for home use after initial training; most extensively studied agent 6, 7
Reslizumab (Intravenous)
- Dosing: 3 mg/kg intravenously every 4 weeks, administered over 20-50 minutes in a healthcare setting 8
- Mechanism: Binds directly to IL-5, similar to mepolizumab 8, 9
- Critical Warning: Anaphylaxis occurred in 0.3% of patients; requires administration by healthcare professionals prepared to manage life-threatening anaphylaxis 8
- Disadvantages: Requires IV infusion in clinic; weight-based dosing adds complexity 8, 6
Benralizumab
- Mechanism: Targets the IL-5 receptor-α directly on eosinophils, causing cytolytic depletion through antibody-dependent cell-mediated cytotoxicity 5, 7
- Efficacy: May achieve more complete eosinophil depletion compared to anti-IL-5 antibodies due to direct cytolytic action 7
- Evidence: Reported effective in case reports and case series; can be considered in patients refractory to mepolizumab 1, 5
Practical Selection Strategy
Start with mepolizumab 100 mg subcutaneously every 4 weeks as first-line anti-IL-5 therapy due to ease of administration, extensive clinical trial data, and favorable safety profile. 4, 6, 7
- Reserve reslizumab for patients who cannot tolerate subcutaneous injections or prefer supervised administration, but ensure capability to manage anaphylaxis 8
- Consider benralizumab or alternative anti-IL-5 agents in patients with inadequate response to mepolizumab after 4-6 months of therapy 1, 5
Monitoring and Dose Adjustments
Expected Timeline for Response
- Blood eosinophil reduction occurs within 4 weeks and should be documented to confirm pharmacodynamic effect 4
- Clinical improvement in exacerbation frequency typically becomes apparent after 3-4 months of therapy 5, 6
- Reassess asthma control at 2-6 weeks after initiating any controller therapy change using validated questionnaires (Asthma Control Test) 2
Oral Corticosteroid Tapering
Do not discontinue systemic or inhaled corticosteroids abruptly upon initiating anti-IL-5 therapy; taper gradually only after demonstrating clinical stability. 8
- Anti-IL-5 biologics enable oral corticosteroid dose reduction of ≥50% in approximately 20% more patients compared to placebo 6
- Aim to reduce oral prednisone to <7.5 mg daily or discontinue entirely while maintaining asthma control 1
Special Considerations and Pitfalls
Common Errors to Avoid
- Do not initiate biologics without first optimizing ICS/LABA therapy and confirming adherence and proper inhaler technique 2, 10
- Do not substitute one anti-IL-5 agent for another without allowing adequate trial duration (minimum 4-6 months) to assess efficacy 5, 7
- Do not use anti-IL-5 therapy for acute bronchospasm or status asthmaticus; these agents are maintenance therapies only 8
Helminth Infections
- Treat pre-existing helminth infections before initiating anti-IL-5 therapy, as eosinophils play a role in parasitic defense 8
- If patients develop helminth infection during treatment and do not respond to anti-helminth therapy, discontinue anti-IL-5 until infection resolves 8
Specialist Referral
Refer patients requiring Step 5-6 therapy (high-dose ICS/LABA plus additional controller) or those being considered for biologic therapies to a specialized severe asthma center. 2, 10