What is the optimal routine management of metered-dose inhalers (MDIs) for a patient with severe asthma on Benralizumab (anti-interleukin-5 receptor alpha subunit monoclonal antibody)?

Management of MDIs in Patients on Benralizumab

Patients on benralizumab should continue their maintenance inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) without reduction initially, with monitoring focused on asthma control, lung function, and oral corticosteroid reduction every 4-8 weeks, allowing for gradual step-down of inhaled therapy only after achieving sustained control for at least 3 months.

Continuation of Baseline Inhaled Therapy

• Do not discontinue or reduce ICS/LABA combinations when initiating benralizumab, as these remain the foundation of severe asthma management and benralizumab is an add-on therapy 1, 2.
• Patients should maintain their high-dose ICS/LABA regimen that was in place prior to benralizumab initiation, as the biologic works synergistically with these controllers 3.
• Short-acting beta-agonist (SABA) MDIs should remain available for rescue use, though frequency of use should decrease as benralizumab takes effect 4.

Monitoring Schedule and Parameters

Initial Phase (First 3 Months)

• Assess patients every 4 weeks during the loading phase (first three doses of benralizumab are given every 4 weeks) 2, 5.
• Monitor the following at each visit:
  • Asthma Control Test (ACT) or Asthma Control Questionnaire-6 (ACQ-6) scores to quantify symptom control 3
  • Pre-bronchodilator FEV1 to assess lung function improvement 3
  • SABA rescue inhaler use frequency (goal: less than 2-3 times daily) 4
  • Blood eosinophil counts (expect near-complete depletion within days to weeks) 2, 6
  • Oral corticosteroid dosage if applicable 5

Maintenance Phase (After 3 Months)

• Continue monitoring every 8 weeks once patients transition to the maintenance dosing schedule (every 8 weeks after first three doses) 5, 3.
• Reassess the same parameters listed above at each visit 3.
• Evaluate for clinical remission at 6 and 12 months, defined as: zero exacerbations, zero OCS use, ACQ-6 ≤0.75, and FEV1 improvement ≥100 mL 3.

Step-Down Strategy for Inhaled Medications

When to Consider Reduction

• Only after achieving well-controlled asthma for at least 3 months with minimal symptoms, no exacerbations, minimal SABA use, and no activity limitations 4.
• Clinical remission criteria should guide step-down decisions: ACQ-6 score ≤0.75, zero exacerbations, and sustained lung function improvement 3.

How to Step Down

• Reduce ICS dose first before considering LABA discontinuation, following standard asthma step-down protocols 4.
• Decrease by one step at a time (e.g., from high-dose to medium-dose ICS/LABA) 4.
• Monitor closely for 1-3 months after each step-down before considering further reductions 4.
• If SABA use increases to more than 2-3 times daily or symptoms worsen, immediately step back up to the previous regimen 4.

Critical Monitoring Points

Rapid Response Indicators

• Expect improvements as early as after the first dose, with striking changes typically seen after 2-3 doses 2.
• Blood eosinophils should deplete to near-zero within days 2, 6.
• Lung function improvements (FEV1 increases) may be evident within the first month 2.

Red Flags Requiring Intervention

• Increased SABA use (>2-3 times daily) indicates loss of control and need to reassess therapy 4.
• Any exacerbation warrants immediate evaluation and potential adjustment of the treatment plan 3.
• Worsening ACQ-6 scores or declining lung function should prompt reconsideration of any recent step-down attempts 3.

Long-Term Management Considerations

• Benralizumab effects are sustained over 1.5-2 years with continued treatment, maintaining exacerbation reduction and OCS-sparing effects 5.
• The safety profile remains acceptable with long-term use, with no new safety signals emerging over extended treatment periods 5.
• Annual evaluation at minimum is recommended even for patients with well-controlled intermittent symptoms 4.
• Approximately 14.5% of patients achieve complete clinical remission by 12 months, which should be the ultimate treatment goal 3.

Common Pitfalls to Avoid

• Do not prematurely reduce inhaled therapy in the first 3 months, even if patients report feeling better, as benralizumab requires time to achieve full effect 2, 3.
• Do not discontinue SABA rescue inhalers, as they remain essential for breakthrough symptoms despite biologic therapy 4.
• Avoid stepping down more than one level at a time, as this increases risk of loss of control 4.