ModifiedUnitedHealthcarePolicy CS2O25DOOS5W

Respiratory Interleukins (Cinqair, Fasenra & Nucala)

Medical Benefit Drug Policy governing provider-administered use of benralizumab (Fasenra), reslizumab (Cinqair), and mepolizumab (Nucala) for eosinophilic respiratory conditions (EGPA, severe eosinophilic asthma, HES, CRSwNP, and COPD); affects providers who administer these drugs and reviewers authorizing coverage.

Policy Summary

PayerUnitedHealthcare

PolicyRespiratory Interleukins (Cinqair, Fasenra & Nucala)

Policy CodePolicy CS2O25DOOS5W

Change TypeCoverage criteria revisedCOPD indication added for Nucala

Effective DateSep 1, 2025

Next Review DateN/A

Key ActionSubmit prior authorization with documentation of diagnosis, baseline eosinophil count and spirometry (for COPD) and attest if patient cannot self-administer.

SourceLink

POLICY UPDATE CHANGES

Replaced criterion requiring 'the patient is not receiving any of [the listed therapies] in combination with Cinqair/Fasenra/Nucala' with 'the patient is not receiving any of [the listed therapies] in combination with Cinqair/Fasenra/Nucala for treatment of the same indication'.

Removed language indicating Nucala is unproven and not medically necessary for the treatment of chronic obstructive pulmonary disease (COPD).

Changed initial authorization duration from '6 months' to '12 months' for the treatment of CRSwNP and HES.

Added detailed COPD coverage criteria for Nucala, including spirometric thresholds, eosinophil cutoffs, exacerbation history, and requirement for concurrent inhaled therapy.

Nucala is proven for patients with COPD meeting specific spirometric, eosinophilic, and exacerbation-history criteria and is to be used as add-on maintenance therapy in combination with specific inhaled regimens.

ICD-10 diagnosis codes J44.0, J44.1, and J44.9 were added to the applicable codes list.

Requirements for provider administration (healthcare professional-administered doses) including circumstances necessitating HCP administration and direct monitoring were added (e.g., hypersensitivity history, patient inability to self-administer, new-to-therapy initial monitored dose).

Patients must not receive Nucala concurrently with other specified biologic therapies for the same indication (e.g., reslizumab, benralizumab, omalizumab, dupilumab, tezepelumab).

3drugs referenced

12 monthsinitial auth duration (most)

150 cells/µLeosinophil threshold (general)

>=300COPD eosinophil threshold

J2182, J0517, J2786included HCPCS/J-codes

Coverage Criteria and Medical Necessity

Initial Therapy - Fasenra for EGPA

Covered when ALL of the following are met

EGPA diagnosis and phenotype: Diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) with past medical history or presence of asthma and histopathologic evidence including at least two characteristic features (eosinophilic vasculitis; eosinophil-rich granulomatous inflammation; perivascular eosinophilic infiltration; neuropathy; sino-nasal abnormality; pulmonary infiltrates non-fixed; cardiomyopathy; alveolar hemorrhage; glomerulonephritis; palpable purpura)

Includes ANCA positive status as noted in policy

Relapse/refractory criteria: Relapsing disease (≥1 relapse in past 2 years requiring increased corticosteroids/immunosuppressant or hospitalization) OR refractory disease (failure to attain remission within 6 months after induction with standard therapy)

Concurrent therapy and administration: Patient is currently receiving standard therapy (systemic glucocorticoids ± immunosuppressive therapy); physician attestation that patient/caregiver cannot self-administer OR one of: documented severe hypersensitivity to Fasenra within past 6 months requiring HCP administration and monitoring; or new to therapy requiring an initial monitored dose (authorization for 1 dose)

Patient must not be receiving Fasenra in combination with other listed biologics for the same indication

Prescriber and dosing: Dosing is in accordance with FDA‑approved labeling; prescribed by a pulmonologist, rheumatologist, or allergist/immunologist; initial authorization will be for no more than 12 months<= 12 months

Initial Therapy - Nucala for EGPA

Covered when ALL of the following are met

EGPA diagnosis and phenotype: Diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) with past medical history or presence of asthma and histopathologic evidence including at least two characteristic features (eosinophilic vasculitis; perivascular eosinophilic infiltration; neuropathy; eosinophil-rich granulomatous inflammation; pulmonary infiltrates non-fixed; cardiomyopathy; sino-nasal abnormality; glomerulonephritis; palpable purpura; alveolar hemorrhage)

Includes ANCA positive status as noted in policy

Relapse/refractory criteria: Relapsing disease (≥1 relapse in past 2 years requiring additional or dose escalation of corticosteroids or immunosuppressant, or hospitalization) OR refractory disease (failure to attain remission within 6 months after induction)

Concurrent therapy and administration: Patient is currently receiving standard therapy (systemic glucocorticoids ± immunosuppressive therapy); physician attestation that patient/caregiver cannot self-administer OR one of: documented severe hypersensitivity to Nucala within past 6 months requiring HCP administration and monitoring; or new to therapy requiring an initial monitored dose (authorization for 1 dose)

Patient must not be receiving Nucala in combination with other listed biologics for the same indication

Initial Therapy - Cinqair for Severe Asthma

Covered when ALL of the following are met

Severity and control: Diagnosis of severe asthma that is uncontrolled or inadequately controlled as defined by at least one: ≥2 bursts of systemic corticosteroids in prior 12 months; poor symptom control (ACQ>1.5 or ACT<20); asthma‑related emergency treatment; or reduced FEV1

Oral corticosteroid dependence: Patient is currently dependent on maintenance oral corticosteroids for asthma

Eosinophilic phenotype: Baseline (pre-reslizumab) peripheral blood eosinophil level ≥150 cells/µL>= 150 cells/µL

Concomitant controller therapy: Use of maximally‑dosed ICS/LABA combination or maximally‑dosed ICS plus an additional controller medication; contraindication/intolerance to Fasenra or Nucala or history of failure to a 4‑month trial of Fasenra or Nucala may be required

Exclusions and dosing: Not to be used in combination with other specified biologics for the same indication; dosing per FDA labeling; initial authorization will be for no more than 12 months; prescribed by a pulmonologist or allergist/immunologist<= 12 months

Initial Therapy - Fasenra/Nucala for Severe Asthma

Covered when ALL of the following are met

Control criteria (any): Poor symptom control (ACQ>1.5 or ACT<20) OR uncontrolled asthma as defined by exacerbation history or reduced FEV1

Oral corticosteroid dependence and eosinophilia: Patient currently dependent on maintenance oral corticosteroids; baseline peripheral blood eosinophils ≥150 cells/µL>= 150 cells/µL

Concomitant controller therapy: Use with one maximally‑dosed ICS (or maximally‑dosed ICS/LABA combination) and possibly an additional controller medication

Administration exceptions: Provider administration required if patient/caregiver cannot self‑administer, severe hypersensitivity in past 6 months, or initial monitored dose; for Nucala provider administration rules include age <11 years as specified

Initial authorization commonly ≤12 months; prescriber specialty required

Exclusion of concomitant biologics: Patient must not be receiving the product in combination with other specified biologics for the same indication (other anti‑IL‑5s, anti‑IL‑4, anti‑IgE, TSLP inhibitors)

Reauthorization/Continuation Criteria

Reauthorization approved when ALL of the following are met

Clinical response (>=1): Documentation of positive clinical response demonstrated by reduction in frequency/severity of relapses OR disease remission OR reduction/discontinuation of corticosteroids/immunosuppressant OR reduction in severity/frequency of disease‑related symptoms (EGPA)

Asthma response (>=1): Documentation of response for asthma including reduction in exacerbations OR increase in percent predicted FEV1 OR decreased rescue medication use OR reduction in asthma symptom frequency/severity

Administration/patient status: Physician attestation that patient/caregiver cannot self‑administer OR documented severe hypersensitivity requiring provider administration; Nucala specific: patient <11 years may require provider administration; Cinqair specific: prior failure to 4‑month trial of Fasenra or Nucala may be required

Reauthorization durations commonly ≤12 months

Exclusion of concomitant biologics: Patient not receiving the product in combination with other specified biologics for the same indication

HES — Initial Therapy

Covered when ALL of the following are met

HES diagnosis duration: Diagnosis of hypereosinophilic syndrome (HES) for ≥6 months

Exclude secondary causes: No identifiable non‑hematologic secondary cause of HES (e.g., drug hypersensitivity, parasitic infection, HIV, non‑hematologic malignancy)

Molecular exclusion: HES is not FIP1L1‑PDGFRA kinase‑positive

Baseline eosinophils: Baseline (pre‑mepolizumab) blood eosinophil level ≥1,000 cells/µL within the past 4 weeks>= 1000 cells/µL

Administration supervision reasons: One of: physician attestation that patient/caregiver cannot self‑administer; new to therapy requiring initial monitored dose (authorization for 1 dose); documented severe hypersensitivity to Nucala within past 6 months requiring monitored administration

Stable background therapy: Patient currently receiving stable dose of background HES therapy (e.g., oral corticosteroid, immunosuppressant, or cytotoxic therapy)

No concurrent biologics: Patient is not receiving Nucala in combination with other specified biologics for the same indication (anti‑IgE, anti‑IL‑4, TSLP inhibitors, other anti‑IL‑5s)

Dosing is in accordance with FDA‑approved labeling

Prescriber specialty: Prescribed by allergist, immunologist, hematologist, cardiologist, or pulmonologist

Authorization length: Initial authorization will be for no more than 12 months<= 12 months

HES — Reauthorization

Reauthorization/Continuation criteria — ALL required

Clinical response: Documentation of positive clinical response demonstrated by reduction in frequency of HES flares

Background therapy: Maintenance or reduction in background HES therapy requirements

Administration supervision reasons: One of: documented severe hypersensitivity within past 6 months requiring monitoring; physician attestation inability to self‑administer; or documented need related to therapy initiation

No concurrent specified biologics: Patient is not receiving Nucala in combination with other specified biologics for the same indication (anti‑IL‑4, TSLP inhibitors, or other anti‑IL‑5s)

Dosing per FDA labeling

Authorization length: Reauthorization will be for no more than 12 months<= 12 months

CRSwNP — Initial Therapy

Covered when ALL of the following are met

Diagnosis definition: Diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP) defined by nasal mucopurulent discharge and two or more symptoms >12 weeks (nasal obstruction, loss of smell, facial pain/pressure)

Objective findings: Either purulent mucus or edema in the middle meatus/ethmoid OR nasal endoscopy/CT showing polyps or mucosal thickening/opacification

Polyp presentation: Presence of bilateral nasal polyposis OR prior surgical removal of bilateral nasal polyps

Prior therapy: One of: prior sinus surgery OR inability to obtain relief after trial of two classes of agents OR required systemic corticosteroids for CRSwNP in previous 2 years

Add-on therapy: Patient will receive Nucala as add‑on maintenance therapy in combination with intranasal corticosteroids

Administration supervision reasons: One of: physician attestation inability to self‑administer; documented severe hypersensitivity within past 6 months requiring monitoring; patient <11 years; new to therapy requiring initial monitored dose (authorization for 1 dose)

No concurrent biologics: Patient is not receiving Nucala in combination with other specified biologics for the same indication (other anti‑IL‑5s, anti‑IL‑4, anti‑IgE, TSLP inhibitors)

Prescriber specialty: Prescribed by allergist/immunologist, otolaryngologist, or pulmonologist

Dosing per FDA labeling

Authorization length: Initial authorization will be for no more than 12 months<= 12 months

CRSwNP — Reauthorization

Reauthorization/Continuation criteria — ALL required

Positive clinical response: Documentation of positive clinical response to Nucala therapy

Continued add-on therapy: Patient will continue Nucala as add‑on maintenance therapy with intranasal corticosteroids

No concurrent biologics: Patient is not receiving Nucala in combination with other specified biologics for the same indication

Dosing per FDA labeling

Authorization length: Reauthorization will be for no more than 12 months<= 12 months

COPD — Initial Therapy

Covered when ALL of the following are met

COPD spirometry: Post‑bronchodilator FEV1/FVC ratio < 0.7FEV1/FVC < 0.7

spirometry must be documented

Eosinophilic phenotype: Baseline (pre‑mepolizumab) peripheral blood eosinophil level ≥300 cells/µL>= 300 cells/µL

value must be pre‑treatment

FEV1 percent: Post‑bronchodilator FEV1 % predicted ≥30% and ≤70%30%-70%

Uncontrolled disease: Two or more COPD exacerbations in previous year requiring systemic corticosteroids/antibiotics OR one or more exacerbations resulting in hospitalization/observation >24 hours2+ moderate OR 1 severe in past year

exacerbations must have occurred despite maintenance therapy

Prior maintenance therapy: Exacerbations occurred while on maintenance therapy with triple therapy (LAMA+LABA+ICS) OR on dual LAMA+LABA with failure/contraindication/intolerance to ICS

Symptom duration: Symptoms of chronic productive cough for at least 3 months in the past year

Add‑on therapy: Nucala will be used as add‑on maintenance therapy in combination with specified inhaled regimens

Administration supervision reasons: One of: physician attestation inability to self‑administer; new to therapy requiring initial monitored dose (authorization for 1 dose); documented severe hypersensitivity within past 6 months requiring monitoring

No concurrent biologics: Patient is not receiving Nucala in combination with other specified biologics for the same indication

Prescriber specialty: Prescribed by an allergist/immunologist or pulmonologist

Authorization length: Initial authorization will be for no more than 12 months<= 12 months

COPD — Reauthorization

Reauthorization/Continuation criteria — ALL required

Documentation of positive response: Documentation of positive clinical response to Nucala therapy

Medication use and dosing: Dosing per FDA labeling; continue as add‑on to inhaled regimens; not in combination with disallowed biologics

Administration supervision reasons: One of: physician attestation inability to self‑administer; documented severe hypersensitivity within past 6 months requiring monitoring

No concurrent biologics: Patient is not receiving Nucala in combination with other specified biologics for the same indication

Authorization length: Reauthorization will be for no more than 12 months<= 12 months

Unproven and Not Medically Necessary

Unproven uses list: Cinqair, Fasenra, and Nucala are unproven and not medically necessary for other eosinophilic conditions, acute bronchospasm, status asthmaticus, granulomatosis with polyangiitis, organ‑ or life‑threatening EGPA, microscopic polyangiitis; additionally Cinqair and Fasenra are unproven and not medically necessary for COPD

Indication-specific trial-based criteria / Clinical coverage context

Clinical indications and trial-based inclusion criteria described for each condition/agent:

EGPA (mepolizumab or benralizumab): Trials enrolled patients with relapsing or refractory EGPA and asthma; required eosinophilia (e.g., ≥1,000 cells/µL or >10% leukocytes) and background prednisone/prednisolone ± immunosuppressive therapy; mepolizumab 300 mg SC every 4 weeks increased accrued weeks of remission vs placebo; benralizumab demonstrated noninferiority to mepolizumab in a head‑to‑head trialeosinophilia as per trial

Severe eosinophilic asthma (benralizumab): Benralizumab pivotal trials (SIROCCO, CALIMA) enrolled patients with ≥2 exacerbations in prior 12 months and baseline blood eosinophils commonly ≥300 cells/µL for primary analyses; trials demonstrated reductions in exacerbation rates and OCS‑sparing>=300 cells/µL in primary analyses; >=150 cells/µL for some endpoints

Severe eosinophilic asthma (mepolizumab): Mepolizumab trials required prior exacerbations and blood eosinophil thresholds commonly ≥150 cells/µL at screening or ≥300 cells/µL within 12 months; demonstrated fewer exacerbations and OCS dose reductions>=150 or >=300 cells/µL depending on trial

Severe eosinophilic asthma (reslizumab): Reslizumab pivotal studies enrolled adults with baseline blood eosinophils ≥400 cells/µL and history of ≥1 exacerbation in prior 12 months; reslizumab 3 mg/kg IV every 4 weeks reduced exacerbation rates>=400 cells/µL

Hypereosinophilic Syndrome (mepolizumab): Mepolizumab HES trial required disease ≥6 months, ≥2 HES flares in prior 12 months, baseline blood eosinophils ≥1,000 cells/µL, and stable background HES therapy; mepolizumab 300 mg SC every 4 weeks reduced HES flares vs placebo; trial excluded FIP1L1‑PDGFRA positive and certain secondary causes>=1,000 cells/µL; >=2 flares in prior 12 months

CRSwNP (mepolizumab): CRSwNP trials required ≥8 weeks of background nasal corticosteroid, prior nasal polypectomy within 10 years, nasal obstruction VAS >5/10, and endoscopic bilateral NPS ≥5 with ≥2 per side; Nucala 100 mg SC every 4 weeks was evaluatedNPS >=5 with >=2 per cavity; VAS >5; prior nasal corticosteroid >=8 weeks

Initial therapy — Nucala for COPD

Covered when ALL of the following are met for Nucala use in COPD:

COPD diagnosis and spirometry: Post‑bronchodilator FEV1/FVC ratio < 0.7 AND post‑bronchodilator FEV1 % predicted ≥30% and ≤70%FEV1/FVC < 0.7; FEV1 30–70% predicted

spirometry must be documented

Eosinophilic phenotype: Baseline (pre‑mepolizumab) peripheral blood eosinophil level ≥300 cells/µL>= 300 cells/µL

value must be pre‑treatment

Exacerbation history: Either: two or more moderate COPD exacerbations in the previous year OR one severe exacerbation requiring hospitalization/observation >24 hours in the previous year2+ moderate OR 1 severe in past year

exacerbations must have occurred despite maintenance therapy

Inadequate control on maintenance inhaled therapy: Exacerbations occurred while receiving maintenance therapy with triple therapy (LAMA+LABA+ICS) OR on dual LAMA+LABA with failure/contraindication/intolerance to an ICS; or symptoms of chronic productive cough for at least 3 months in the past yearconcurrent inhaled therapy documented

Nucala is add‑on maintenance therapy

Treatment setting and prescribing: Nucala used as add‑on maintenance therapy in combination with specified inhaled regimens; dosing in accordance with FDA labeling; prescribed by an allergist/immunologist or pulmonologistper FDA label

initial authorization up to 12 months

Administration/monitoring exceptions

Covered when ANY of the following administration/monitoring conditions are met:

Provider administration reasons: Patient or caregiver is not competent or physically unable to self‑administer; documented severe hypersensitivity to Nucala within past 6 months requiring monitored administration; patient is new to therapy and requires observed first dose (authorization for 1 dose)administration/monitoring documented

authorization for initial observed dose will be for 1 dose

Initial therapy for eosinophilic COPD

Covered when ALL of the following are met

COPD diagnosis and spirometry: Post‑bronchodilator FEV1/FVC ratio < 0.7 AND post‑bronchodilator FEV1 % predicted ≥30% and ≤70%FEV1/FVC < 0.7; FEV1 30-70% predicted

Clinical spirometry required

Eosinophilic phenotype: Baseline (pre‑treatment) peripheral blood eosinophil level ≥300 cells/µL>= 300 cells/µL

Laboratory documentation required

Uncontrolled COPD evidence: Either: Two or more COPD exacerbations in the previous year requiring systemic corticosteroids and/or antibiotics or observation over 24 hours OR COPD exacerbations occurred while receiving maintenance therapy with specified inhaled regimens OR symptoms of chronic productive cough for at least 3 months in the past year2+ exacerbations or exacerbation on maintenance therapy or chronic productive cough >=3 months

Exacerbation history or symptom documentation required

Concomitant maintenance therapy: Nucala will be used as add‑on maintenance therapy in combination with either triple therapy (LAMA+LABA+ICS) OR dual therapy (LAMA+LABA) with failure/contraindication/intolerance to an ICSconcomitant inhaled maintenance regimen documented

Medication list or regimen documentation required

Reauthorization / continuation

Covered for continued use when ALL of the following are met

Positive clinical response: Documentation of positive clinical response to Nucala therapyclinical improvement documented

Provider must document response

Dosing and prescriber: Dosing in accordance with FDA labeling AND prescribed by an allergist/immunologist or pulmonologistFDA‑label dosing and specialist prescriber

Reauthorization limited to no more than 12 months

Requests for these interleukin-targeting biologics must comply with combination-therapy rules. Patients must not receive Cinqair, Fasenra, or Nucala concurrently with another listed biologic for the same indication (examples include other anti-IL-5 agents, anti-IL-4 therapies, anti-IgE therapies, and TSLP inhibitors). Failure to adhere to this restriction is an explicit exclusion and may result in denial. Dosing must also follow FDA labeling and prescriber specialty requirements as specified in the policy.

The policy lists several uses that are considered unproven and not medically necessary for Cinqair, Fasenra, and Nucala. Examples include: acute bronchospasm, status asthmaticus, and other non‑labeled eosinophilic conditions (e.g., granulomatosis with polyangiitis, microscopic polyangiitis, organ- or life‑threatening EGPA). Additionally, Cinqair and Fasenra are explicitly noted as unproven/not medically necessary for COPD.

When considering Nucala for hypereosinophilic syndrome (HES), the clinical trial populations excluded non‑hematologic secondary causes of eosinophilia. Examples of excluded secondary causes include drug hypersensitivity, parasitic (helminth) infection, HIV infection, non‑hematologic malignancy, and molecularly defined FIP1L1‑PDGFRA kinase–positive HES. These exclusions are referenced in the HES trial and incorporated into the policy's coverage criteria.

Cinqair, Fasenra, and Nucala are not indicated for acute relief of bronchospasm or for management of status asthmaticus; the FDA labels and this policy state these agents are maintenance therapies for eosinophilic disease, not rescue agents. Requests for use in acute bronchospasm/status asthmaticus or similar emergent scenarios will be considered not medically necessary.

Concurrent administration of Nucala with another biologic for treatment of the same indication (for example, reslizumab, benralizumab, omalizumab, dupilumab, or tezepelumab) is prohibited and will trigger denial. The policy clarifies that the prohibition applies specifically to combination therapy for the same clinical indication rather than any concurrent biologic use for unrelated conditions.

All dosing must be consistent with the FDA‑approved labeling for each product. The policy emphasizes that approvals require documentation of the appropriate disease phenotype and severity — for example, an eosinophilic asthma phenotype (baseline blood eosinophils >= 150 cells/µL for many asthma indications) or indication‑specific thresholds described in the criteria. Nonconcordant dosing or failure to meet phenotype/severity requirements are grounds for denial.

The policy states that Cinqair and Fasenra are considered unproven and not medically necessary for COPD. For COPD-related requests, the document distinguishes that only Nucala has defined COPD coverage criteria; absence of those criteria for Cinqair or Fasenra means they are not supported for COPD.

Inclusion of HCPCS or ICD‑10 codes in the policy is informational and does not guarantee coverage or reimbursement. Benefit determinations remain subject to federal, state, and contractual requirements and other policies; coding inclusion alone is not authorization.

The policy lists other eosinophilic conditions as unproven uses for these agents. Examples called out include disorders beyond the labeled indications; acute bronchospasm and status asthmaticus are specifically noted as not established indications. These uses are considered not medically necessary.

Applicable Codes and Clinical Thresholds

Applicable codes (not listed)mixed

NDC/HPC/other not listed in this section

No explicit HCPCS/CPT/NDC codes provided in this partial document

Applicable HCPCS and select diagnosis codes (group 1)mixed

J0517	Injection; benralizumab, mg.
J2182	Injection, mepolizumab, 1 mg.
J2786	Injection , reslizumab , 1 mg
D72.11	Hypereosinophilic Syndrome
J31.0	Chronic rhinitis

Applicable diagnosis codes (group 2)ICD-10

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
J33.1	Polypoid sinus degeneration
J33.8	Other polyp of sinus

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Biologic HCPCS codesHCPCS

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

Diagnosis codes referenced in policyICD-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.

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Applicable ICD-10 CodesICD-10

J44.0	Chronic obstructive pulmonary disease with acute lower respiratory infection
J44.1	Chronic obstructive pulmonary disease with (acute) exacerbation
J44.9	Chronic obstructive pulmonary disease, unspecified

Peripheral blood eosinophil count (general asthma threshold)

DefinitionBaseline (pre-treatment) peripheral blood eosinophil level ≥ 150 cells/µL defines the eosinophilic asthma phenotype used for eligibility in severe asthma indications.

ContextApplied to severe eosinophilic asthma criteria for Fasenra, Nucala, and Cinqair as referenced in trial enrollment and coverage criteria.

Actionable thresholdUse pre-treatment peripheral blood eosinophil ≥150 cells/µL to identify eosinophilic asthma phenotype for coverage consideration.

COPD blood eosinophil threshold — >= 300 cells/µL

COPD eosinophil threshold>= 300 cells/µL (baseline pre‑treatment peripheral blood eosinophil level required for Nucala eligibility in COPD).

Policy useThreshold operationalized in COPD coverage criteria to define the eosinophilic COPD phenotype for mepolizumab (Nucala).

DocumentationMust be a pre‑treatment (baseline) laboratory value submitted with authorization request.

HES baseline blood eosinophil — >= 1,000 cells/µL

HES baseline eosinophil threshold>= 1,000 cells/µL (baseline pre‑treatment peripheral blood eosinophil level within the past 4 weeks) required for Nucala in HES trial/coverage criteria.

Trial contextHES pivotal trial enrolled patients with blood eosinophil ≥1,000 cells/µL and ≥2 flares in prior 12 months; coverage mirrors this threshold.

DocumentationLaboratory evidence of the ≥1,000 cells/µL value must be submitted (chart notes, labs).

Blood eosinophil count thresholds used in trials — varied thresholds by indication/trial

Common trial thresholdsTrials used varying eosinophil cutoffs: commonly ≥150 cells/µL (some mepolizumab asthma trials), ≥300 cells/µL (benralizumab primary analyses, some mepolizumab criteria), and ≥400 cells/µL (reslizumab pivotal studies).

HES-specificHES trial required baseline blood eosinophil ≥1,000 cells/µL and ≥2 HES flares in prior 12 months.

Actionable noteUse the trial-specific eosinophil cutoff corresponding to the indication when assessing eligibility (e.g., ≥150 for some asthma approvals; ≥300 for COPD analyses; ≥1,000 for HES).

Endoscopic bilateral nasal polyp score (NPS) threshold used in CRSwNP

NPS threshold>= 5 total endoscopic bilateral nasal polyp score (NPS) with ≥2 in each nasal cavity was required in the CRSwNP trial enrollment and is referenced in coverage criteria.

Trial requirementsPatients also required prior nasal corticosteroid use (≥8 weeks) and prior nasal polypectomy in many participants; NPS scoring was 0–8 (0–4 per side).

DocumentationEndoscopic NPS must be documented when used to support CRSwNP eligibility for Nucala.

Peripheral blood eosinophil count (COPD policy restatement) >= 300 cells/µL

Restated COPD eosinophil threshold>= 300 cells/µL (baseline pre‑treatment) — policy restates this as the required eosinophil cutoff for COPD Nucala eligibility.

Role in eligibilityDefines eosinophilic COPD phenotype and is required alongside spirometry and exacerbation history for coverage consideration.

Post-bronchodilator FEV1/FVC ratio requirement for COPD (< 0.7)

FEV1/FVC requirementPost‑bronchodilator FEV1/FVC ratio < 0.7 is required to document persistent airflow limitation consistent with COPD for Nucala eligibility.

PurposeUsed to confirm COPD diagnosis (persistent airflow limitation) in coverage criteria.

DocumentationPost‑bronchodilator spirometry report must be submitted with the authorization request.

Post-bronchodilator FEV1 % predicted requirement for COPD (30-70%)

FEV1 % predicted requirementPost‑bronchodilator FEV1 percent predicted ≥30% and ≤70% is required for COPD Nucala eligibility.

ContextThis range operationalizes disease severity in the COPD coverage criteria alongside FEV1/FVC <0.7 and eosinophil threshold.

DocumentationSubmit post‑bronchodilator FEV1 percent predicted from spirometry as part of authorization documentation.

Baseline peripheral blood eosinophil level (COPD) >= 300 cells/µL

Baseline eosinophil (COPD)>= 300 cells/µL (baseline, pre‑mepolizumab) required for COPD Nucala coverage.

Documentation timingValue must be obtained prior to initiation of mepolizumab and submitted with the request.

AssociationUsed together with spirometric and exacerbation criteria to define eosinophilic COPD eligible for Nucala.

Post-bronchodilator FEV1/FVC ratio (COPD restated) < 0.7

FEV1/FVC restatedPost‑bronchodilator FEV1/FVC ratio < 0.7 (restated) — required to confirm COPD diagnosis in policy criteria.

Clinical roleConfirms persistent airflow limitation distinct from reversible airway disease (asthma).

DocumentationInclude post‑bronchodilator spirometry with authorization request to demonstrate this value.

Post-bronchodilator FEV1 % predicted (COPD restated) 30-70%

FEV1 % predicted restatedPost‑bronchodilator FEV1 percent predicted 30–70% (restated) — required range for COPD Nucala eligibility.

Severity mappingThis FEV1 % predicted range helps define the moderate‑to‑severe COPD population targeted by the policy.

Submission requirementProvide the spirometry report showing post‑bronchodilator FEV1 % predicted within this range.

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required — provider-administered agents and coding note

Prior authorization is required for provider-administered biologic agents referenced in this policy. Inclusion of HCPCS/ICD-10 codes in this policy is for informational billing purposes only and does not guarantee coverage, reimbursement, or payment. Benefit coverage is determined by member contract, federal/state law, and other applicable policies.

Prior authorization required for provider-administered agents (e.g., J0517, J2182, J2786).
Inclusion of codes does NOT imply authorization or guarantee payment; other policies and contractual limits may apply.

Billing Rule

Prior Authorization with Applicable Codes

Certain HCPCS J-codes and ICD-10 diagnosis codes are associated with requests for provider-administered biologic therapy and should be included on prior authorization requests when applicable.

HCPCS: J0517 (benralizumab injection, per mg); J2182 (mepolizumab injection, 1 mg); J2786 (reslizumab injection, 1 mg).
ICD-10 examples relevant to indications: J44.0, J44.1, J44.9 (COPD); J45.50–J45.52 (severe asthma); J33.* (nasal polyps); D72.11 (HES); J31.0, J32.* series (sinusitis).

Prior Authorization

Prior Authorization and Duration — initial authorization limited to 12 months

Initial prior authorization for provider-administered biologic therapy will generally be limited to no more than 12 months for covered indications. Reauthorization/continuation requests must document ongoing medical necessity and response to therapy. Single-dose in-office administration may be authorized for patients who require direct monitoring or cannot self-administer; such authorizations may be limited to one monitored dose when indicated.

Initial authorization duration: up to 12 months for indications including severe asthma, CRSwNP, HES, and COPD where applicable.
Single monitored in-office dose authorization: approved when physician attests patient/caregiver cannot self-administer or patient is new to therapy and requires observation (authorization for 1 dose).
Reauthorization: up to 12 months when criteria for continuation are met and positive clinical response is documented.

Documentation Required

Required Clinical Documentation and Supporting Records

Comprehensive clinical documentation is required with all prior authorization requests to demonstrate that the member meets indication-specific coverage criteria.

Diagnosis and indication-specific diagnostic evidence (e.g., confirmed diagnosis of EGPA, severe eosinophilic asthma, CRSwNP, HES, or COPD).
Phenotype or biomarker documentation (baseline peripheral blood eosinophil count with date and value).
Objective disease severity measures where applicable (e.g., ACQ or ACT scores for asthma; post-bronchodilator spirometry: FEV1/FVC ratio and FEV1 % predicted for COPD).
History of exacerbations or flares (e.g., systemic steroid bursts, hospitalizations, documented HES flares).
Prior treatment history including trials of and response/intolerance to other biologics, inhaled controllers, intranasal corticosteroids, oral corticosteroids, sinus surgery when relevant.
Physician specialty attestation (e.g., pulmonologist, allergist/immunologist, hematologist, cardiologist) and rationale for in-office administration if requested.

Step Therapy

Step Therapy and Conservative-Therapy Expectations

The policy specifies expected conservative-therapy and step-therapy prerequisites prior to approval for biologic therapy for specific indications. Documentation of prior trials, failures, contraindications, or intolerance must be provided.

CRSwNP: Trial of intranasal corticosteroids and at least two classes of conservative therapies (e.g., nasal saline irrigation, antileukotriene agents, oral corticosteroids) and prior sinus surgery or failed medical therapy as specified.
Severe asthma: Maximally-dosed inhaled therapy required — e.g., one maximally-dosed combination ICS/LABA product or maximally-dosed ICS plus an additional controller; evidence of inadequate control (exacerbations, ACQ/ACT scores) or OCS dependence.
Cinqair (reslizumab): Prior failure, contraindication, or intolerance to Fasenra or Nucala, or documented failure to a 4-month trial of Fasenra or Nucala when applicable.
For COPD: documentation of maintenance inhaled therapy and treatment failure per criteria (see COPD-specific callout).

Documentation Required

Required Background and Concomitant Inhaled Therapy for Nucala in COPD

Nucala (mepolizumab) use for COPD requires demonstration of specific background inhaled maintenance therapy and objective diagnostic testing.

Required background inhaled therapy prior to Nucala for COPD: use as add-on maintenance therapy in combination with one of the following: triple therapy (LAMA + LABA + ICS) or dual therapy (LAMA + LABA) with documented failure, contraindication, or intolerance to an ICS when dual therapy is used.
Required objective testing and documentation: post-bronchodilator FEV1/FVC ratio < 0.7; post-bronchodilator FEV1 % predicted ≥30% and ≤70%; baseline peripheral blood eosinophil count ≥300 cells/µL (pre-treatment); documentation of exacerbation history (≥2 exacerbations treated with systemic corticosteroids and/or antibiotics in prior year, or ≥1 exacerbation resulting in hospitalization/observation >24 hours).
Nucala must be used as add-on maintenance therapy to the specified inhaled regimens; include medication names/doses and dates in the PA submission.

Background and Clinical Context

Background: These products are interleukin‑targeting biologic therapies used as add‑on maintenance treatments for eosinophilic respiratory diseases. Fasenra (benralizumab) and Nucala (mepolizumab) are provided subcutaneously for provider administration; Cinqair (reslizumab) is administered intravenously. Indications covered in this policy include eosinophilic granulomatosis with polyangiitis (EGPA), severe eosinophilic asthma, hypereosinophilic syndrome (HES), chronic rhinosinusitis with nasal polyps (CRSwNP), and — for Nucala only — an eosinophilic COPD phenotype meeting the policy's specified criteria.

Definitions and Clinical Terms

Relapsing or refractory EGPA — definition key value

DefinitionRelapsing EGPA: at least one EGPA relapse within the past 2 years requiring increased corticosteroids, immunosuppressant, or hospitalization; Refractory EGPA: failure to attain remission within 6 months after induction therapy.

Clinical elementsRelapsing or refractory status usually accompanied by history/presence of asthma and histopathologic features (≥2 characteristic EGPA findings).

DocumentationMedical record documentation of relapse/refractory history and relevant histopathology/ANCA status should be submitted for authorization.

Eosinophilic asthma phenotype definition — >=150 cells/µL threshold

Eosinophilic asthma definitionAsthma with baseline (pre‑treatment) peripheral blood eosinophil level ≥150 cells/µL.

Clinical contextUsed to identify eosinophilic phenotype in severe asthma coverage criteria for Fasenra and Nucala.

Trial alignmentSome trials and indications use higher thresholds (e.g., ≥300 cells/µL) for primary analyses; check indication‑specific criteria.

Eosinophilic phenotype (COPD/HES) definitions — COPD >=300; HES >=1000

COPD definitionCOPD eosinophilic phenotype: baseline peripheral blood eosinophils ≥300 cells/µL (policy operational threshold).

HES definitionHES baseline threshold: blood eosinophils ≥1,000 cells/µL and disease duration ≥6 months (trial and policy requirement).

Clinical implicationThese thresholds are used to align coverage decisions with trial enrollment criteria for each condition.

Eosinophilic phenotype general description — epidemiology note

General descriptionEosinophilic phenotype refers to airway/pulmonary disease subtypes associated with elevated blood and airway eosinophils; approximately half of severe asthma patients exhibit this phenotype.

Epidemiology noteAsthma affects ~24 million people in the U.S.; an estimated 1.2–2.4 million have severe asthma, and about half of those have eosinophilic phenotype.

Clinical relevanceEosinophil levels guide selection of anti‑IL‑5 therapies and are correlated with trial response in many studies.

Hypereosinophilic Syndrome (HES) definition — clinical threshold and chronicity

HES definitionHypereosinophilic Syndrome (HES) is a disorder of sustained eosinophil overproduction causing organ damage; many patients have >1,500 eosinophils/µL for 6 months or more, and trial/policy criteria require disease ≥6 months and exclusion of secondary causes.

ExclusionsTrials and policy exclude non‑hematologic secondary causes (e.g., drug hypersensitivity, parasitic infection, HIV, non‑hematologic malignancy) and FIP1L1‑PDGFRA–positive patients.

Treatment contextMepolizumab (Nucala) was studied at 300 mg SC every 4 weeks in HES patients meeting these criteria and reduced HES flares in the trial.

CRSwNP definition — disease duration and NPS requirements from trials

CRSwNP definitionChronic rhinosinusitis with nasal polyps is an inflammatory condition lasting ≥12 weeks; trial enrollment required inadequate response to nasal corticosteroids and endoscopic bilateral NPS ≥5 with ≥2 per cavity.

Other trial requirementsPatients had prior nasal corticosteroid use (≥8 weeks) and many had prior nasal polypectomy within 10 years.

Objective measuresNPS is scored 0–4 per side (total 0–8); documentation of endoscopic scores supports coverage for Nucala in CRSwNP.

Severe eosinophilic asthma definition — uncontrolled despite optimized therapy and eosinophil thresholds

Severe eosinophilic asthma definitionAsthma uncontrolled despite optimized high‑dose ICS‑LABA and management of contributory factors, characterized by elevated blood eosinophils (commonly thresholds referenced at ≥150–300 cells/µL).

Clinical featuresMay include frequent exacerbations, poor symptom control (ACQ>1.5 or ACT<20), reduced FEV1, or maintenance OCS dependence.

Use in policyDefinition underpins eligibility for biologic therapies (Fasenra, Nucala, Cinqair) in severe asthma criteria.

COPD eosinophilic phenotype definition for this policy (>=300 cells/µL)

Policy COPD eosinophilic phenotypeFor COPD in this policy, eosinophilic phenotype is defined as baseline peripheral blood eosinophil level ≥300 cells/µL prior to mepolizumab treatment.

Operational noteThis threshold is required along with spirometry and exacerbation history for Nucala coverage in COPD.

DocumentationSubmit baseline eosinophil laboratory result obtained before initiating Nucala.

Baseline peripheral blood eosinophil level >= 300 cells/µL — short definition

Short definition>= 300 cells/µL (baseline peripheral blood eosinophil level) used to identify eosinophilic phenotype for COPD Nucala eligibility.

Required timingValue must be pre‑treatment (baseline) and documented in submitted records.

Use caseApplies specifically to COPD coverage criteria for mepolizumab in this policy.

COPD spirometric criteria — post-bronchodilator FEV1/FVC <0.7 and FEV1 % predicted 30-70%

Spirometric criteriaPost‑bronchodilator FEV1/FVC ratio < 0.7 and post‑bronchodilator FEV1 percent predicted 30–70% are the spirometric requirements to document COPD severity for Nucala eligibility.

PurposeThese criteria confirm persistent airflow limitation and moderate‑to‑severe airflow obstruction consistent with COPD coverage population.

SubmissionProvide full post‑bronchodilator spirometry report showing both FEV1/FVC and FEV1 % predicted values with the authorization request.

Policy Revision History

2025-09-01revisionLatest

Revised coverage criteria: clarified that exclusion of combination therapy applies to use for the same indication; removed language stating Nucala was unproven/not medically necessary for COPD; changed initial authorization duration to 12 months for CRSwNP and HES; added COPD-specific coverage criteria and provider administration/monitoring requirements; added ICD-10 codes J44.0, J44.1, and J44.9.

note

Policy history entries on 09/01/2025 include multiple related operational and clinical updates (see full summary).

Policy Summary

PayerUnitedHealthcare

PolicyRespiratory Interleukins (Cinqair, Fasenra & Nucala)

Policy CodePolicy CS2O25DOOS5W

Change TypeCoverage criteria revisedCOPD indication added for Nucala

Effective DateSep 1, 2025

Next Review DateN/A

Key ActionSubmit prior authorization with documentation of diagnosis, baseline eosinophil count and spirometry (for COPD) and attest if patient cannot self-administer.

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