UnitedHealthcare respiratory interleukins Coverage Update

Coverage Criteria and Medical Necessity

Fasenra - Severe eosinophilic asthma

Fasenra for severe eosinophilic asthma — Covered when ALL of the following are met

Fasenra initial therapy criteria: Diagnosis of severe asthma; classification of asthma as uncontrolled or inadequately controlled as defined by at least one measure (e.g., ACQ >1.5 or ACT <20, ≥2 systemic corticosteroid bursts in prior 12 months, asthma-related emergency treatment, airflow limitation such as FEV1 <80% predicted with reduced FEV1/FVC); eosinophilic phenotype with baseline (pre-treatment) peripheral blood eosinophils ≥ 150 cells/μL; will be used as add-on maintenance therapy with a maximally dosed ICS/LABA or a maximally dosed ICS plus an additional controller; patient is not receiving Fasenra in combination with other listed biologics for the same indication (e.g., Nucala, Cinqair, Xolair, Dupixent, Tezspire); dosing per FDA labeling; prescribed by a pulmonologist or allergist/immunologist; initial authorization ≤ 12 monthseosinophils >= 150 cells/μL

Uncontrolled defined by ACQ>1.5 or ACT<20, ≥2 steroid bursts, ER/hospital visits, airflow limitation, or maintenance OCS dependence

Cinqair (reslizumab) - Severe eosinophilic asthma

Cinqair for severe eosinophilic asthma — Covered when ALL of the following are met

Cinqair initial therapy criteria: Diagnosis of severe asthma; classification of asthma as uncontrolled or inadequately controlled as defined by at least one measure (e.g., ACQ >1.5 or ACT <20, ≥2 systemic corticosteroid bursts in prior 12 months, asthma-related emergency treatment, airflow limitation, or maintenance OCS dependence); eosinophilic phenotype with baseline (pre-reslizumab) peripheral blood eosinophils ≥ 150 cells/μL; will be used as add-on maintenance therapy in combination with an ICS-containing maintenance medication or appropriate combination controller regimens; history of failure to a 4-month trial of Fasenra or Nucala OR documented contraindication/intolerance to those agents; history of failure to a 4-month trial of Tezspire OR documented contraindication/intolerance to Tezspire; patient is not receiving Cinqair in combination with other listed biologics for the same indication (e.g., Nucala, Fasenra, Xolair, Dupixent, Tezspire); dosing per FDA labeling; prescribed by a pulmonologist or allergist/immunologist; initial authorization ≤ 12 monthseosinophils >= 150 cells/μL

Nucala (mepolizumab) - Severe eosinophilic asthma

Nucala for severe eosinophilic asthma — Covered when ALL of the following are met

Nucala initial therapy criteria: Diagnosis of severe asthma; classification of asthma as uncontrolled or inadequately controlled as defined by at least one measure (e.g., ACQ >1.5 or ACT <20, ≥2 systemic corticosteroid bursts in prior 12 months, asthma-related emergency treatment, airflow limitation, or maintenance OCS dependence); eosinophilic phenotype with baseline (pre-treatment) peripheral blood eosinophils ≥ 150 cells/μL; will be used as add-on maintenance therapy in combination with a maximally dosed ICS/LABA or appropriate controller regimen; patient is not receiving Nucala in combination with other listed biologics for the same indication (e.g., Cinqair, Fasenra, Xolair, Dupixent, Tezspire); dosing per FDA labeling; prescribed by a pulmonologist or allergist/immunologist; initial authorization ≤ 12 monthseosinophils >= 150 cells/μL

EGPA - Fasenra and Nucala

Fasenra and Nucala for EGPA — Covered when ALL of the following are met

EGPA criteria for Fasenra/Nucala (initial): Diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA); past medical history or presence of asthma; presence of at least two typical EGPA characteristics (e.g., histopathologic evidence such as eosinophilic vasculitis, perivascular eosinophilic infiltration, eosinophil-rich granulomatous inflammation; neuropathy; pulmonary infiltrates; sino-nasal abnormality; cardiomyopathy; glomerulonephritis; alveolar hemorrhage; palpable purpura; or ANCA positivity); history of relapsing disease (≥1 relapse in prior 2 years requiring escalation of corticosteroids/immunosuppressant or hospitalization) OR refractory disease (failure to attain remission within prior 6 months after induction therapy); patient currently taking standard therapy (systemic glucocorticoids ± immunosuppressive therapy); patient is not receiving Fasenra or Nucala in combination with other listed biologics for same indication (e.g., other anti-IL‑5, anti-IgE, anti-IL‑4, TSLP inhibitors); dosing per FDA labeling; prescribed by a pulmonologist, rheumatologist, or allergist/immunologist; initial authorization ≤ 12 months

Reauthorization/Continuation criteria

Reauthorization/Continuation of Care — Covered when ALL of the following are met

Reauthorization criteria (asthma and EGPA): Documentation of positive clinical response demonstrated by at least one specified improvement (e.g., reduction in frequency/severity of relapses or exacerbations, reduction or discontinuation of corticosteroids or immunosuppressants, disease remission, decreased rescue medication use, increase in percent predicted FEV1, or reduction in symptom severity/frequency); patient is not receiving prohibited concurrent biologic therapy for the same indication; dosing per FDA labeling; reauthorization ≤ 12 months

Severe eosinophilic asthma — initial and reauthorization combined criteria

Covered when ALL of the following are met for initiation; reauthorization requires documented clinical response.

Asthma initial criteria: Patient will receive Nucala as add-on maintenance therapy in combination with an ICS-containing maintenance medication or appropriate controller regimen; prescribed by a pulmonologist or allergist/immunologist; dosing per FDA labeling; initial authorization ≤ 12 months; patient is not receiving Nucala in combination with other listed biologics for the same indication

Asthma reauthorization: Documentation of positive clinical response demonstrated by at least one of: reduction in exacerbations, decreased rescue medication use, increase in percent predicted FEV1 from pretreatment baseline, or reduction in asthma-related symptoms; dosing per FDA labeling; reauthorization ≤ 12 months

Hypereosinophilic Syndrome (HES) — initial and reauthorization

Nucala is medically necessary for HES when all specified diagnostic and lab criteria are met; reauthorization requires clinical response.

HES initial criteria: Diagnosis of hypereosinophilic syndrome (HES) for ≥ 6 months; no identifiable non-hematologic secondary cause; HES is not FIP1L1-PDGFRα kinase-positive; submission of medical records documenting baseline (pre-mepolizumab) blood eosinophil level ≥ 1000 cells/µL within the past 4 weeks; patient is on a stable dose of background HES therapy (e.g., oral corticosteroid, immunosuppressant, or cytotoxic therapy); patient is not receiving Nucala in combination with other listed biologics for same indication; dosing per FDA labeling; prescribed by an allergist/immunologist, hematologist, cardiologist, or pulmonologist; initial authorization ≤ 12 monthsbaseline eosinophils >= 1000 cells/µL (within past 4 weeks)

HES reauthorization: Documentation of positive clinical response demonstrated by reduction in frequency of HES flares or maintenance/reduction in background HES therapy requirements; dosing per FDA labeling; reauthorization ≤ 12 months; not combined with other listed biologics

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) — initial and reauthorization

Nucala is medically necessary as add-on maintenance therapy for CRSwNP when diagnostic symptom duration, objective findings, prior therapies, and concomitant intranasal corticosteroids requirements are met.

CRSwNP diagnostic criteria: Diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP) with two or more symptoms for >12 weeks (e.g., nasal mucopurulent discharge, nasal obstruction, facial pain/pressure/fullness, or reduced/loss of smell); objective findings on nasal endoscopy or CT (purulent mucus/edema in middle meatus or ethmoid, polyps, or radiographic mucosal thickening/opacification); presence of bilateral nasal polyposis or prior bilateral polypectomy

CRSwNP prior therapy requirements: One of: prior sinus surgery; systemic corticosteroids for CRSwNP in previous 2 years; or failure to obtain symptom relief after trial of two of the following classes: nasal saline irrigations, intranasal corticosteroids, antileukotriene agents; patient will receive Nucala with intranasal corticosteroids and will not receive Nucala in combination with other listed biologics; prescribed by allergist/immunologist, otolaryngologist, or pulmonologist; initial auth ≤ 12 months

CRSwNP reauthorization: Documentation of positive clinical response to Nucala therapy; continued use as add-on with intranasal corticosteroids; dosing per FDA labeling; reauthorization ≤ 12 months; not combined with other listed biologics

Chronic Obstructive Pulmonary Disease (COPD) — initial and reauthorization

Nucala is medically necessary for COPD with eosinophilic phenotype when spirometric, eosinophil, exacerbation, and concomitant maintenance therapy criteria are met.

COPD diagnostic and spirometry: Post-bronchodilator FEV1/FVC < 0.7 AND post-bronchodilator FEV1 % predicted between 20% and 80% (revised effective 02/01/2026)FEV1/FVC < 0.7; FEV1% >=20% and <=80%

COPD eosinophilic phenotype: Baseline peripheral blood eosinophil level ≥ 300 cells/μL>= 300 cells/μL

COPD exacerbation history: Two or more COPD exacerbations in the previous year requiring systemic corticosteroids and/or antibiotics OR one or more exacerbations leading to hospitalization/observation >24 hours in past year; exacerbations must have occurred while on specified maintenance therapy

Unproven / Not Medically Necessary

Listed uses considered unproven and not medically necessary.

Unproven indications: Acute bronchospasm; Granulomatosis with polyangiitis (Wegener's); Microscopic polyangiitis; Organ- or life-threatening EGPA; Other eosinophilic conditions; Status asthmaticus; (Additionally, Cinqair and Fasenra are listed as unproven and not medically necessary for COPD)

Indications and evidence summaries

Indications and clinical trial evidence summarized (no explicit coverage decision language in these chunks).

EGPA indications (drug labels): Benralizumab and mepolizumab are indicated for treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA).

Severe eosinophilic asthma indications: Benralizumab and mepolizumab are indicated as add-on maintenance treatment for patients ≥6 years with severe eosinophilic asthma; reslizumab is indicated for adults ≥18 years with severe eosinophilic asthma. Trial populations commonly required prior exacerbations and blood eosinophil thresholds (see trial thresholds).

CRSwNP context: CRSwNP is chronic (≥12 weeks); mepolizumab demonstrated benefit in adults with recurrent symptomatic CRSwNP meeting trial entry criteria (e.g., prior nasal corticosteroid use, prior polypectomy, NPS and VAS thresholds).

HES context: Mepolizumab reduces eosinophil production and has mechanistic rationale in HES where sustained eosinophilia causes organ damage; HES trials required baseline eosinophils >=1000 cells/µL and prior flares.

Trial-supported candidate coverage populations

Evidence-based populations and endpoints from trials supporting use:

Reslizumab (Cinqair) pivotal studies: Adults ≥18 years with severe eosinophilic asthma; primary studies required screening blood eosinophils ≥ 400 cells/µL and ≥1 exacerbation in prior 12 months (Studies I-II); reslizumab 3 mg/kg IV q4w reduced exacerbation rates and OCS-requiring/hospitalization exacerbations in pivotal trials.blood eosinophil >=400 cells/μL

Mepolizumab (Nucala) HES trial: Patients ≥12 years with HES ≥6 months, blood eosinophils ≥1000 cells/µL at screening, on stable background HES therapy, and ≥2 HES flares in prior 12 months; mepolizumab 300 mg SC q4w reduced flares vs placebo over 32 weeks.blood eosinophil >=1000 cells/μL

Mepolizumab for CRSwNP trial: Adults ≥18 years with recurrent symptomatic CRSwNP required prior nasal corticosteroid ≥8 weeks, prior polypectomy within 10 years, nasal obstruction VAS >5/10 and bilateral NPS ≥5 (≥2 each cavity); Nucala 100 mg SC q4w improved NPS and VAS and reduced need for surgery and systemic steroids.

Chronic Obstructive Pulmonary Disorder (COPD) — revised criterion

Revisions to COPD medical necessity criteria as of 02/01/2026

COPD FEV1% criterion (revised): Diagnosis of COPD defined by post-bronchodilator FEV1 % predicted greater than or equal to 20% and less than or equal to 80% (replaced prior range of ≥30% to ≤70%).FEV1 % predicted >=20% and <=80%

Patient must not receive any listed biologic in combination with another listed biologic for the treatment of the same indication. Examples of excluded concurrent therapies include other anti‑IL‑5 agents (e.g., Nucala/mepolizumab, Fasenra/benralizumab, Cinqair/reslizumab), anti‑IgE therapy (e.g., Xolair/omalizumab), anti‑IL‑4 therapy (e.g., Dupixent/dupilumab), and TSLP inhibitors (e.g., Tezspire/tezepelumab). This exclusion applies to initial requests and reauthorization of care; dosing must follow FDA labeling and prescriber specialty requirements remain applicable.

For Nucala specifically, the patient must not be receiving Nucala in combination with any other listed biologic for treatment of the same indication. Listed examples include anti‑IL‑5 agents (e.g., Cinqair/reslizumab, Fasenra/benralizumab), anti‑IgE therapy (e.g., Xolair/omalizumab), anti‑IL‑4 therapy (e.g., Dupixent/dupilumab), and TSLP inhibitors (e.g., Tezspire/tezepelumab). Requests that document concurrent use of these agents for the same diagnosis may be denied.

The inclusion of a procedure or diagnosis code in this policy is for reference only and does not imply that the service described by the code is a covered benefit. Benefit coverage is determined by the member specific benefit plan document and by applicable federal or state laws; the policy does not itself guarantee coverage or reimbursement.

These anti‑interleukin agents are not indicated for immediate relief of acute bronchospasm or for treatment of status asthmaticus. In addition, reslizumab (Cinqair) labeling includes a warning regarding the risk of anaphylaxis; providers administering Cinqair should observe patients and be prepared to manage anaphylaxis.

Nucala (mepolizumab) is not indicated for relief of acute bronchospasm or for the treatment of status asthmaticus.

The following uses are considered unproven and not medically necessary pending robust randomized controlled trial evidence: acute bronchospasm, status asthmaticus, other eosinophilic conditions listed in FDA labeling, granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis, and organ‑ or life‑threatening EGPA. Cinqair and Nucala are also not indicated for these acute uses per FDA labeling.

Some document sections provide lists of unproven or non‑covered uses but do not explicitly use the phrase 'not medically necessary' in every chunk. Reviewers should apply the policy’s unproven‑indication statements and the member benefit plan when determining coverage decisions.

Use of Nucala, Cinqair, or Fasenra for other eosinophilic conditions outside labeled indications, as well as for acute bronchospasm or status asthmaticus, is considered unproven and not medically necessary according to this policy pending demonstration of safety and efficacy in statistically robust randomized controlled trials.

The policy revision dated 02/01/2026 removed the prior COPD symptom requirement for chronic productive cough (≥3 months in the past year). That requirement is no longer part of the COPD medical necessity criteria.

Applicable Billing and Diagnosis Codes

Applicable HCPCS codesHCPCS

J0517	Injection, benralizumab, 1 mg.
J2182	Injection, mepolizumab, 1 mg.
J2786	Injection, reslizumab, 1 mg

Biologic drug HCPCS codesHCPCS

J0517	Injection, benralizumab, 1 mg.
J2182	Injection, mepolizumab, 1 mg.
J2786	Injection, reslizumab, 1 mg

Applicable ICD-10 and HCPCS (continued)mixed

D72.11	Hypereosinophilic Syndrome.
J31.0	Chronic rhinitis.
J32.0	Chronic maxillary sinusitis.
J32.1	Chronic frontal sinusitis.
J32.2	Chronic ethmoidal sinusitis.
J32.3	Chronic sphenoidal sinusitis.
J32.4	Chronic pansinusitis.
J32.8	Other chronic sinusitis.
J32.9	Chronic sinusitis, unspecified.
J33.0	Polyp of nasal cavity.

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Applicable ICD-10 codes (additional)ICD-10

J45.52	Severe persistent asthma with status asthmaticus.
J82.81	Chronic eosinophilic pneumonia.
J82.82	Acute eosinophilic pneumonia.
J82.83	Eosinophilic asthma.
J82.89	Other pulmonary eosinophilia, not elsewhere classified.
M30.1	Polyarteritis with lung involvement [Churg-Strauss]

Biologic drug HCPCS codesHCPCS

J0517	Injection, benralizumab, 1 mg.
J2182	Injection, mepolizumab, 1 mg.
J2786	Injection, reslizumab, 1 mg

Diagnosis codes (partial list)ICD-10

D72.11	Hypereosinophilic Syndrome.
J31.0	Chronic rhinitis.
J32.0	Chronic maxillary sinusitis.
J32.1	Chronic frontal sinusitis.
J32.2	Chronic ethmoidal sinusitis.
J32.3	Chronic sphenoidal sinusitis.
J32.4	Chronic pansinusitis.
J32.8	Other chronic sinusitis.
J32.9	Chronic sinusitis, unspecified.
J33.0	Polyp of nasal cavity.

1–10 of 18

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Additional diagnosis codesICD-10

J45.52	Severe persistent asthma with status asthmaticus.
J82.81	Chronic eosinophilic pneumonia.
J82.82	Acute eosinophilic pneumonia.
J82.83	Eosinophilic asthma.
J82.89	Other pulmonary eosinophilia, not elsewhere classified.
M30.1	Polyarteritis with lung involvement [Churg-Strauss]

Peripheral blood eosinophil threshold — key value (asthma)

Peripheral blood eosinophil threshold≥ 150 cells/μL

ContextDefines eosinophilic phenotype for severe asthma across Fasenra, Cinqair, and Nucala criteria

Use for screening vs trial criteriaUsed as baseline (pre-treatment) peripheral blood eosinophil cutoff for coverage eligibility and trial enrollment

HES baseline eosinophil — key value

HES baseline eosinophil requirement≥ 1000 cells/µL within the past 4 weeks

Prior Authorization, Documentation, and Prescriber Responsibilities

Prior Authorization

Prior Authorization Required — verify biologic drug codes and plan coverage

Prior authorization is required. Providers must verify plan-level prior authorization and benefit coverage for biologic agents prior to administration and billing. Confirm member-specific benefits (medical vs. pharmacy), applicable Medicare Part B furnishing rules for MA members, and any plan-specific step therapy or quantity limits.

Verify prior authorization and benefit type for J0517 (benralizumab), J2182 (mepolizumab), J2786 (reslizumab)
Check member-specific plan documents for medical vs pharmacy coverage and any step therapy (Medicare Part B Step Therapy may apply)
For Medicare Advantage members, confirm Part B furnishing rules when no NCD/LCD exists

Prior Authorization

Prior Authorization Required for FDA-Indicated Uses

Prior authorization is required for all FDA-indicated uses of these agents. Submit documentation demonstrating the FDA-approved indication and age range for the specific drug (e.g., reslizumab for severe eosinophilic asthma in adults ≥18; benralizumab and mepolizumab for severe eosinophilic asthma in children/adolescents per labeling; mepolizumab has additional FDA indications for EGPA, HES, COPD, and CRSwNP as labeled).

Background, Indications, and Rationale

Background: These agents are monoclonal anti‑interleukin therapies used as add‑on maintenance treatments for severe eosinophilic asthma and, for some agents, additional eosinophilic disorders. Indications across the class include severe eosinophilic asthma (age limits vary by agent), and for mepolizumab (Nucala) additional FDA‑approved indications include eosinophilic granulomatosis with polyangiitis (EGPA), hypereosinophilic syndrome (HES), eosinophilic COPD, and chronic rhinosinusitis with nasal polyps (CRSwNP). Their mechanism targets the IL‑5 pathway to reduce eosinophil activity and counts.

Definitions and Key Clinical Terms

Relapsing or refractory EGPA — definition

DefinitionRelapsing or refractory EGPA: relapsing = ≥1 relapse in prior 2 years requiring increased corticosteroids, immunosuppressant, or hospitalization; refractory = failure to attain remission within prior 6 months after induction therapy

Supporting clinical featuresDiagnosis requires EGPA plus history/presence of asthma and ≥2 typical EGPA characteristics (e.g., eosinophilic vasculitis, neuropathy, pulmonary infiltrates, sino‑nasal abnormality, cardiomyopathy, glomerulonephritis, alveolar hemorrhage, palpable purpura, ANCA positivity)

Prescriber specialtyTherapies indicated for EGPA require specialist prescribers (pulmonologist, rheumatologist, or allergist/immunologist per criteria)

Eosinophilic phenotype (asthma) — key value

Eosinophilic phenotype (asthma) thresholdBaseline peripheral blood eosinophil level ≥ 150 cells/μL

Policy Revision History

2026-02-01policy_revisionLatest

Revised COPD medical necessity criteria: changed post-bronchodilator FEV1 % predicted range from ≥30%–≤70% to ≥20%–≤80% and removed the prior requirement for symptoms of chronic productive cough for at least 3 months in the past year; previous policy version 2025D0055W archived.

Related/archive note: Medicare does not have a National Coverage Determination (NCD) for respiratory interleukin biologics; no LCDs/LCAs were identified. Providers must verify member‑specific prior authorization and coverage rules. The policy history shows a material revision on 02/01/2026 with COPD criteria changes and the previous policy version archived as 2025D0055W.

OpenPayer

Respiratory Interleukins (Cinqair®, Fasenra®, & Nucala®)