Is subcutaneous administration of 2 NUCALA (mepolizumab) 100 MG-ML injections every 4 weeks medically indicated for a patient with eosinophilic asthma and Chronic Obstructive Pulmonary Disease (COPD), presenting with symptoms of congestion, shortness of breath, and elevated eosinophil count, currently using Breztri (budesonide, glycopyrrolate, and formoterol)?

Medical Indication Assessment for Nucala in Eosinophilic Asthma with COPD

Yes, Nucala (mepolizumab) 100 mg subcutaneously every 4 weeks is medically indicated for this patient with eosinophilic asthma, elevated eosinophil count (520 cells/μL), and persistent symptoms despite triple inhaled therapy (Breztri). This dosing regimen is FDA-approved for severe eosinophilic asthma and is supported by clinical trial evidence demonstrating reduced exacerbations and improved asthma control 1.

FDA-Approved Indication and Dosing

• The FDA-approved dose for severe eosinophilic asthma in adults is 100 mg subcutaneously every 4 weeks, administered to the upper arm, thigh, or abdomen 1.
• The patient's prescription of "2 NUCALA 100 MG-ML" injections (totaling 200 mg) every 4 weeks exceeds the FDA-approved dose for asthma and requires clarification 1.
• 300 mg every 4 weeks (administered as three separate 100-mg injections) is reserved for EGPA and hypereosinophilic syndrome, not for severe asthma alone 1.

Clinical Rationale for This Patient

The patient meets criteria for mepolizumab based on:

• Eosinophilic phenotype confirmed with blood eosinophil count of 520 cells/μL (well above the typical threshold of ≥150-300 cells/μL used in clinical trials) 2, 3.
• Persistent symptoms (congestion, shortness of breath) despite optimized triple inhaled therapy with Breztri (ICS/LABA/LAMA combination) 1.
• Severe asthma diagnosis requiring add-on biologic therapy 1, 4.

Evidence for Mepolizumab in Eosinophilic Asthma

Mepolizumab 100 mg every 4 weeks significantly reduces:

• Asthma exacerbation rates by approximately 50% compared to placebo in patients with severe eosinophilic asthma 4.
• Oral corticosteroid requirements in steroid-dependent patients, with meaningful dose reductions achieved 4.
• Improves asthma control and quality of life as measured by validated instruments 4.

Consideration of Concurrent COPD

The presence of COPD with eosinophilic phenotype provides additional support for mepolizumab:

• Mepolizumab 100 mg every 4 weeks reduces moderate or severe COPD exacerbations in patients with blood eosinophil counts ≥150 cells/μL (rate ratio 0.79-0.80 vs. placebo) 2, 3.
• The 2025 MATINEE trial demonstrated that mepolizumab added to triple inhaled therapy in COPD patients with eosinophil counts ≥300 cells/μL reduced annualized exacerbation rates from 1.01 to 0.80 events per year 3.
• This patient's eosinophil count of 520 cells/μL places them in the higher-benefit subgroup where mepolizumab shows greater efficacy for both asthma and COPD manifestations 2, 3.

Critical Dosing Clarification Required

The prescribed dose of 200 mg (2 injections) every 4 weeks is not standard for asthma:

• For severe eosinophilic asthma alone: 100 mg every 4 weeks is the FDA-approved dose 1.
• For EGPA (if diagnosed): 300 mg every 4 weeks (three 100-mg injections spaced ≥5 cm apart) is required 1, 5.
• The provider should clarify whether:
  • The patient has undiagnosed EGPA (which would require 300 mg, not 200 mg) 5, 6
  • The prescription contains a dosing error (should be 100 mg for asthma)
  • There is clinical rationale for off-label intermediate dosing

EGPA Screening Considerations

Before finalizing the dose, evaluate for EGPA features:

• EGPA diagnostic criteria include: asthma, eosinophilia >10% or absolute count >1,500 cells/μL, and vasculitic manifestations affecting ≥2 extrapulmonary organs 5.
• This patient's presentation (congestion, asthma, eosinophilia of 520 cells/μL) could represent:
  • Severe eosinophilic asthma with rhinosinusitis (most likely)
  • Early or limited EGPA (requires further evaluation for systemic manifestations)
• If EGPA is confirmed, the dose must be increased to 300 mg every 4 weeks 5, 6, 1.

Safety and Monitoring

Mepolizumab has a favorable safety profile:

• Most common adverse event is headache, with overall tolerability similar to placebo 4.
• Monitor patients after administration in line with standard practice for biologic agents 1.
• Do not use for acute bronchospasm or status asthmaticus—this is maintenance therapy only 1.

Recommendation

Approve mepolizumab for this patient with eosinophilic asthma and COPD, but correct the dose to 100 mg subcutaneously every 4 weeks unless EGPA is diagnosed, which would require 300 mg every 4 weeks 1. The patient's elevated eosinophil count, persistent symptoms despite triple therapy, and dual diagnosis of eosinophilic asthma and COPD make them an ideal candidate for anti-IL-5 therapy 2, 4, 3. The prescribed 200 mg dose does not align with FDA-approved regimens and requires provider clarification before dispensing 1.