ModifiedUnitedHealthcarePolicy CS2026D0055Y

Respiratory Interleukins (Cinqair, Fasenra, & Nucala)

Medical benefit drug policy governing provider-administered Cinqair (reslizumab), Fasenra (benralizumab), and Nucala (mepolizumab) for treatment of eosinophilic asthma and eosinophilic granulomatosis with polyangiitis (EGPA); affects clinicians prescribing or administering these agents under UnitedHealthcare plans.

Policy Summary

PayerUnitedHealthcare

PolicyRespiratory Interleukins (Cinqair, Fasenra, & Nucala)

Policy CodePolicy CS2026D0055Y

Change TypeTemplate updateoperational editsarchive/revision

Effective DateApril 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with indication-specific documentation including baseline peripheral blood eosinophil level and evidence of uncontrolled disease or prior controller therapy failure.

SourceLink

POLICY UPDATE CHANGES

Removed content/language pertaining to the state of Louisiana.

Template Update.

Archived previous policy version CS2026D0055X.

3drugs covered

>=150eosinophil threshold (asthma)

12 motypical init auth (most)

6 moNucala init auth (EGPA)

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4distinct indications

Coverage Criteria by Agent and Indication

Fasenra for EGPA — Initial (provider-administered)

Proven and medically necessary when ALL of the following are met:

Primary diagnosis

EGPA characteristic features: Eosinophilic vasculitis; Perivascular eosinophilic infiltration; Eosinophil-rich granulomatous inflammation; Neuropathy (mono or poly); Pulmonary infiltrates, non-fixed; Sino-nasal abnormality; Cardiomyopathy (echocardiography or MRI); Glomerulonephritis; Alveolar hemorrhage; Palpable purpura; ANCA positive

Relapsing or refractory disease: Relapsing disease: ≥1 EGPA relapse within past 2 years requiring escalation of corticosteroids/immunosuppressant or hospitalization; OR refractory disease: failure to attain remission within prior 6 months following induction therapy

Concurrent therapy: Patient is currently taking standard therapy (systemic glucocorticoids with or without immunosuppressive therapy)

Provider administration justification: Physician attestation patient/caregiver not competent or physically unable to self-administer; OR documented severe hypersensitivity to Fasenra within past 6 months requiring monitored administration; OR new to therapy requiring initial monitored dose (authorization for 1 dose)

Exclusions: Patient is not receiving Fasenra in combination with other listed biologics for same indication (anti-IL-5, anti-IgE, anti-IL-4, TSLP inhibitor)

Other: Dosing per U.S. FDA labeling; prescribed by pulmonologist, rheumatologist, or allergist/immunologist; initial authorization no more than 12 months

Nucala for EGPA — Initial (provider-administered)

Proven and medically necessary when ALL of the following are met:

Primary diagnosis

EGPA characteristic features: Eosinophilic vasculitis; Perivascular eosinophilic infiltration; Eosinophil-rich granulomatous inflammation; Neuropathy (mono or poly); Pulmonary infiltrates, non-fixed; Sino-nasal abnormality; Cardiomyopathy (echocardiography or MRI); Glomerulonephritis; Alveolar hemorrhage; Palpable purpura; ANCA positive

Concurrent therapy: Patient is currently taking standard therapy (systemic glucocorticoids with or without immunosuppressive therapy)

Cinqair for severe eosinophilic asthma — Initial (IV, provider-administered)

Proven and medically necessary when ALL of the following are met:

Primary diagnosis: Diagnosis of severe asthma

Uncontrolled asthma criteria: Poor symptom control (ACQ>1.5 or ACT<20); OR ≥2 systemic corticosteroid bursts (≥3 days each) in prior 12 months; OR asthma-related emergency treatment or hospitalization; OR airflow limitation (post-withhold FEV1 <80% predicted with reduced FEV1/FVC); OR dependence on maintenance oral corticosteroids

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

Concomitant controller therapy: Used with one maximally-dosed ICS/LABA combination; OR combination of maximally-dosed ICS plus one additional asthma controller medication

Fasenra and Nucala for severe eosinophilic asthma — Initial (provider-administered)

Proven and medically necessary when ALL of the following are met:

Primary diagnosis: Diagnosis of severe asthma

Uncontrolled asthma criteria: Poor symptom control (ACQ>1.5 or ACT<20); OR ≥2 systemic corticosteroid bursts (≥3 days each) in prior 12 months; OR asthma-related emergency treatment/hospitalization; OR airflow limitation (post-withhold FEV1 <80% predicted with reduced FEV1/FVC); OR dependence on maintenance oral corticosteroids

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

Concomitant controller therapy: Used with one maximally-dosed ICS/LABA combination; OR combination therapy of maximally-dosed ICS plus one additional asthma controller medication

Reauthorization/Continuation (Fasenra or Nucala for EGPA)

Authorization for continued use will be approved based on ALL of the following:

Evidence of clinical response: Reduction in frequency and/or severity of relapses; OR reduction or discontinuation of corticosteroids/immunosuppressant; OR disease remission; OR reduction in severity/frequency of EGPA-related symptoms

Ongoing provider administration justification: Physician attestation patient/caregiver not competent or physically unable to self-administer; OR documented severe hypersensitivity within past 6 months requiring monitored administration

Exclusions: Patient is not receiving the product in combination with other listed biologics for same indication

Other: Dosing per U.S. FDA labeling; reauthorization no more than 12 months

Severe eosinophilic asthma — Initial Therapy (provider administration)

Covered when ALL of the following are met

Asthma diagnosis and control: Diagnosis of severe asthma AND classification as uncontrolled/inadequately controlled by at least one: poor symptom control (ACQ>1.5 or ACT<20); OR ≥2 systemic corticosteroid bursts ≥3 days in prior 12 months; OR asthma-related emergency treatment/hospitalization; OR airflow limitation (post-withhold FEV1 <80% predicted with reduced FEV1/FVC); OR dependence on maintenance oral corticosteroids

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

Concomitant controller therapy: Used in combination with either a maximally-dosed ICS/LABA combination OR maximally-dosed ICS plus one additional controller medication

Examples provided in policy

Asthma — Reauthorization/Continuation

Covered when ALL of the following are met

Clinical response: Documentation of positive clinical response: reduction in exacerbations; OR decreased rescue medication use; OR increase in percent predicted FEV1 from pretreatment baseline; OR reduction in severity/frequency of asthma symptoms

Concomitant therapy and exclusions: Continued use with an ICS-containing maintenance medication; AND patient not receiving the product in combination with other listed biologics for same indication

Specific cross-product exclusions vary by product

Administration exceptions for reauth: For Fasenra/Nucala reauthorization: physician attestation patient/caregiver cannot self-administer OR documented severe hypersensitivity within past 6 months OR (Nucala only) patient ≤11 years; For Cinqair reauthorization: history of failure to 4-month trial of Fasenra or Nucala OR contraindication/intolerance to them

Dosing and duration:

Hypereosinophilic syndrome (HES) — Initial Therapy and Reauthorization

Initial therapy covered when ALL of the following are met

Diagnosis duration and exclusions: Diagnosis of HES for ≥6 months; no identifiable nonhematologic secondary cause; HES is not FIP1L1-PDGFRα kinase-positive

Administration exceptions: One of: physician attestation patient/caregiver not competent or physically unable to self-administer; OR documented severe hypersensitivity to Nucala within past 6 months requiring monitored administration; OR new to therapy requiring initial monitored dose (authorization for 1 dose)

Baseline labs and background therapy: Submission of medical records documenting baseline (pre-mepolizumab) blood eosinophil level ≥1,000 cells/µL within past 4 weeks AND patient is receiving a stable dose of background HES therapy>=1,000 cells/µL

No concomitant biologics and prescriber:

Chronic rhinosinusitis with nasal polyps (CRSwNP) — Initial and Reauthorization

Initial therapy covered when ALL of the following are met

Diagnostic symptom criteria: Diagnosis of CRSwNP defined by two or more symptoms >12 weeks: nasal mucopurulent discharge; nasal obstruction/congestion; facial pain/pressure/fullness; reduction or loss of smell

Objective findings: One of: purulent mucus/edema in middle meatus or ethmoid regions; polyps in nasal cavity or middle meatus; CT imaging with mucosal thickening or opacification

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

Prior therapy failure: One of: prior sinus surgery; OR systemic corticosteroids for CRSwNP in previous 2 years; OR inability to obtain symptom relief after trial of two classes of agents (nasal saline irrigations, intranasal corticosteroids, antileukotriene agents)

Chronic Obstructive Pulmonary Disease (COPD) — Initial and Reauthorization

Covered when ALL of the following are met

Spirometric diagnosis: Post-bronchodilator FEV1/FVC ratio <0.7 AND post-bronchodilator FEV1 % predicted ≥20% and ≤80%FEV1/FVC <0.7; FEV1 % predicted 20–80%

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

Uncontrolled disease/exacerbations: Uncontrolled COPD demonstrated by either ≥2 exacerbations in prior year requiring systemic corticosteroids and/or antibiotics OR ≥1 exacerbation resulting in hospitalization/observation >24 hours in past year

Exacerbations occurred on maintenance therapy:

Nucala (mepolizumab) reauthorization for COPD

Reauthorization/Continuation of Care Criteria for patients currently on Nucala for COPD: approval requires ALL of the following

Root: Reauthorization requires all of the following conditions

Clinical response: Documentation of positive clinical response to Nucala therapy

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Concomitant maintenance therapy: Nucala is being used in combination with maintenance therapy (examples: Advair/AirDuo, Bevespi Aerosphere, Breo Ellipta, Symbicort, Trelegy Ellipta)

Chunk 36

Administration capability or hypersensitivity: Either physician attestation that patient/caregiver is not competent or physically unable to self-administer Fasenra or Nucala OR documented history of severe hypersensitivity to Fasenra or Nucala within past 6 months requiring administration and direct monitoring by a healthcare professional

Unproven / Not Medically Necessary uses

Unproven and Not Medically Necessary

Unproven_NMN_list: Cinqair, Fasenra, and Nucala are unproven and not medically necessary for: other eosinophilic conditions; acute bronchospasm; status asthmaticus; granulomatosis with polyangiitis; microscopic polyangiitis; organ- or life-threatening EGPA

Chunk 38

Agent_specific_NMN: Cinqair and Fasenra are unproven and not medically necessary for chronic obstructive pulmonary disease (COPD)

Chunk 38

Reslizumab (Cinqair) initial coverage criteria

Reslizumab (Cinqair) covered when ALL of the following are met

Age: Patient is aged 18 years or older>=18 years

Reslizumab FDA indication is for adults

Diagnosis: Severe asthma with eosinophilic phenotype

Matches FDA indication for add-on maintenance treatment

Evidence of eosinophilia or prior trial criteria: Clinical evidence or lab documentation consistent with trials (e.g., history of exacerbation requiring systemic corticosteroid in prior 12 months; blood eosinophil counts as used in trials, e.g., >=400/µL)eg >=400/µL

Reflects entry criteria from Studies I-II

Mepolizumab (Nucala) coverage criteria by indication

Mepolizumab (Nucala) covered when ALL of the following are met (indication-specific sets summarized)

Severe eosinophilic asthma: Add-on maintenance treatment for patients aged >=6 years with severe asthma and eosinophilic phenotype>=6 years

FDA-approved pediatric age for asthma

EGPA: Treatment for adult patients with eosinophilic granulomatosis with polyangiitis (EGPA)adult

FDA indication

Hypereosinophilic syndrome (HES): Treatment for patients aged >=12 years with HES for >=6 months without identifiable non-hematologic secondary cause>=12 years; >=6 months

FDA-indication-based coverage

Covered when ALL of the following are met for the specified agent and indication:

Fasenra (benralizumab) - covered indications: Add-on maintenance treatment of patients with severe asthma aged 6 years and older with an eosinophilic phenotype; treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA).FDA-approved indications only

Not indicated for other eosinophilic conditions or for acute bronchospasm or status asthmaticus.

Nucala (mepolizumab) - covered indications: Add-on maintenance treatment of patients with severe asthma aged 6 years and older with an eosinophilic phenotype; treatment of adult patients with EGPA; treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) for ≥6 months without an identifiable non-hematologic secondary cause; add-on maintenance treatment of adult patients with inadequately controlled COPD and an eosinophilic phenotype; add-on maintenance treatment of adult patients 18 years and older with chronic rhinosinusitis with nasal polyps (CRSwNP).FDA-approved indications and age requirements

Not indicated for relief of acute bronchospasm or status asthmaticus.

Use of these interleukin-targeted biologics in combination with other specified biologic therapies for the same indication is prohibited. Specifically, the patient must not be receiving concomitant therapy with other anti‑IL‑5 agents (e.g., Nucala, Cinqair), anti‑IgE therapy (e.g., Xolair), anti‑IL‑4 therapy (e.g., Dupixent), or TSLP inhibitors (e.g., Tezspire) when seeking authorization for a given agent. Requests that document concurrent use of two or more of these biologics for the same indication do not meet the coverage criteria.

Nucala (mepolizumab) is not covered when used simultaneously with other biologic therapies for the same indication. Requests for Nucala must demonstrate the patient is not receiving an anti‑IL‑4, another anti‑IL‑5, anti‑IgE, or a TSLP inhibitor for the same diagnosis. Reauthorization for Nucala in indications such as COPD also requires documentation that no concurrent biologic therapy for the same indication is being administered.

Cinqair (reslizumab) and Fasenra (benralizumab) are considered unproven and not medically necessary for the treatment of chronic obstructive pulmonary disease (COPD). Cinqair is FDA‑approved only for add‑on maintenance treatment of severe eosinophilic asthma in adults and is explicitly not indicated for COPD; Fasenra’s label likewise does not support COPD and the policy designates these uses as not medically necessary.

Reslizumab (Cinqair), mepolizumab (Nucala), and benralizumab (Fasenra) are not indicated for the management of acute bronchospasm or status asthmaticus. These agents are indicated as add‑on maintenance therapies for chronic eosinophilic airway diseases and are not appropriate treatments for acute, life‑threatening bronchospasm or status asthmaticus; such use is excluded from coverage.

Use of these agents for acute bronchospasm, status asthmaticus, or for eosinophilic conditions not listed among the FDA‑approved indications is excluded. The policy treats such acute or off‑indication uses as not covered or unproven; robust randomized controlled trial evidence is required before these indications would be considered for coverage. Providers should seek appropriate acute care therapies for bronchospasm rather than these biologic maintenance agents.

Nucala requests that do not meet the policy’s eosinophil thresholds or that lack required background controller therapy will be denied. For eosinophilic phenotype indications the baseline peripheral blood eosinophil level must meet the stated threshold (e.g., ≥150 cells/µL for asthma; higher thresholds apply for other indications), and for asthma/COPD the agent must be used as an add‑on to specified controller regimens. Use outside these numeric thresholds or without the required concomitant controller therapy does not meet coverage criteria.

Use of Cinqair, Fasenra, or Nucala for other eosinophilic conditions (those not listed in the FDA indications) or for acute settings is considered unproven or not medically necessary. The policy requires indication‑specific evidence (typically randomized controlled trial data) before these therapies will be approved for additional eosinophilic disorders or for acute management.

Specifically for Nucala and Cinqair, uses outside the agents’ labeled indications—such as treatment of other eosinophilic syndromes, acute bronchospasm, or status asthmaticus—are viewed as unproven in the absence of randomized controlled trial evidence. The policy notes that additional FDA‑listed or label‑referenced uses require statistically robust RCT data to establish safety and efficacy before coverage will be considered.

Treatment of conditions outside each agent’s FDA‑approved indications (including acute bronchospasm and status asthmaticus) is considered not medically necessary per this policy. Coverage is limited to the FDA‑labeled uses enumerated for each drug; requests for off‑label indications are subject to denial absent compelling evidence meeting the policy’s standards.

Billing and Code References

Referenced HCPCS and ICD-10 codes (part 1)mixed

J0517	Injection, benralizumab, 1 mg
J2182	Injection, mepolizumab, 1 mg
J2786	Injection, reslizumab, 1 mg
D72.11	Hypereosinophilic Syndrome
J31.0	Chronic rhinitis
J32.0	Chronic maxillary sinusitis

Referenced ICD-10 codes (part 2)ICD-10

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
J33.9	Nasal polyp, unspecified

1–10 of 21

1/3

Drug NDCs and product identifiersNDC

NDC (not listed)

Product-specific NDCs not provided in this section

Drug/Indication references (no explicit billing codes in excerpt)mixed

No codes listed

inv-29: Peripheral blood eosinophil level — typical threshold

Typical threshold (asthma/eosinophilic phenotype)>= 150 cells/µL

COPD threshold (baseline)>= 300 cells/µL

HES screening/entry threshold (trial and HES criteria)>= 1,000 cells/µL (within past 4 weeks)

Benralizumab pivotal-trial entry example>= 300 cells/µL

inv-30: Baseline peripheral blood eosinophil level by indication

Asthma (baseline pre-treatment)>= 150 cells/µL

Authorization, Documentation, and Administration Requirements

Prior Authorization

Time-limited initial authorization

Initial authorizations for provider-administered indications are time-limited; most initial approvals are for no more than 12 months (Nucala for EGPA initial authorization is limited to no more than 6 months).

Prior Authorization

Prior authorization required

Prior authorization is required for these biologic therapies; initial approvals are limited in duration and must meet indication-specific clinical and laboratory criteria.

Prior Authorization

Nucala reauthorization criteria

Reauthorization of Nucala for COPD requires documentation of a positive clinical response, continuation with maintenance inhaled therapy, absence of concurrent biologic therapies for the same indication, and dosing per FDA labeling; reauthorization will be for no more than 12 months.

Clinical Background and Rationale

Background: Cinqair (reslizumab), Fasenra (benralizumab), and Nucala (mepolizumab) target the interleukin‑5 pathway or its receptor to reduce eosinophilic inflammation. These agents are indicated primarily for patients with an eosinophilic phenotype of severe asthma and, for certain agents, other eosinophilic diseases (e.g., Nucala for EGPA and HES; Fasenra for EGPA). Patient selection emphasizes documented uncontrolled or severe disease despite optimized controller therapy and an eosinophilic biomarker (for many asthma indications, baseline peripheral blood eosinophils of ≥150 cells/µL), with provider administration required in specific situations such as inability to self‑administer or prior severe hypersensitivity.

Key Definitions and Diagnostic Thresholds

inv-61: Uncontrolled or inadequately controlled asthma — definition elements

Poor symptom control metricACQ > 1.5 or ACT < 20

Frequent systemic corticosteroid burstsTwo or more bursts (>=3 days each) in prior 12 months

Asthma-related acute careEmergency treatment, hospital admission, or unscheduled urgent visit for asthma

inv-62: Relapsing or refractory EGPA — definition elements

Core diagnostic requirementDiagnosis of EGPA with past history or presence of asthma

EGPA characteristic features (need at least two)Eosinophilic vasculitis; perivascular eosinophilic infiltration; eosinophil-rich granulomatous inflammation; neuropathy; pulmonary infiltrates; sino-nasal abnormality; cardiomyopathy; glomerulonephritis; alveolar hemorrhage; palpable purpura; ANCA positive

Policy History and Changes

Policy Summary

PayerUnitedHealthcare

PolicyRespiratory Interleukins (Cinqair, Fasenra, & Nucala)

Policy CodePolicy CS2026D0055Y

Change TypeTemplate updateoperational editsarchive/revision

Effective DateApril 1, 2026

Next Review DateN/A

SourceLink

On This Page

Provider administration justification:

Physician attestation patient/caregiver not competent or physically unable to self-administer; OR documented severe hypersensitivity to Nucala within past 6 months requiring monitored administration; OR new to therapy requiring initial monitored dose (authorization for 1 dose)

Exclusions: Patient is not receiving Nucala in combination with other listed biologics for same indication (anti-IL-4, anti-IL-5, anti-IgE, TSLP inhibitor)

Other: Dosing per U.S. FDA labeling; prescribed by pulmonologist, rheumatologist, or allergist/immunologist; initial authorization no more than 6 months

Prior biologic failure/contraindication: History of failure to a 4-month trial of Fasenra or Nucala; OR contraindication/intolerance to Fasenra or Nucala

Exclusions: Patient is not receiving Cinqair in combination with other listed biologics for same indication (anti-IL-4, anti-IL-5, anti-IgE, TSLP inhibitor)

Other: Dosing per U.S. FDA labeling; prescribed by pulmonologist or allergist/immunologist; initial authorization no more than 12 months

Provider administration justification: Physician attestation patient/caregiver not competent or physically unable to self-administer; OR documented severe hypersensitivity within past 6 months requiring monitored administration; OR new to therapy requiring initial monitored dose (authorization for 1 dose)

Exclusions: Patient is not receiving the agent in combination with other listed biologics for same indication (anti-IL-4, anti-IL-5, anti-IgE, TSLP inhibitor)

Other: Dosing per U.S. FDA labeling; prescribed by pulmonologist or allergist/immunologist; initial authorization no more than 12 months

Administration exceptions:

One of: physician attestation patient/caregiver cannot self-administer; documented severe hypersensitivity to Nucala within past 6 months requiring monitored administration; new to therapy requiring initial monitored dose (authorization for 1 dose); OR patient ≤11 years of age

No concomitant biologics: Patient is not receiving Nucala in combination with anti-IL-4, anti-IL-5, anti-IgE, or TSLP inhibitors for same indication

Dosing and prescriber: Dosing per U.S. FDA labeling; prescribed by pulmonologist or allergist/immunologist; initial authorization no more than 12 months

Dosing per U.S. FDA labeling; reauthorization no more than 12 months

Patient is not receiving Nucala in combination with other listed biologics; dosing per U.S. FDA labeling; prescribed by allergist, immunologist, hematologist, cardiologist, or pulmonologist; initial authorization no more than 12 months

Reauthorization criteria: Documentation of positive clinical response (reduction in HES flares or maintenance/reduction in background HES therapy) AND one of the administration exception conditions; not receiving concomitant listed biologics; dosing per U.S. FDA labeling; reauthorization no more than 12 months

Concomitant therapy and administration exceptions: Nucala as add-on maintenance with intranasal corticosteroids; AND one of administration exceptions (cannot self-administer, severe hypersensitivity within 6 months, new to therapy needing monitored initial dose, or patient ≤11 years)

No concomitant biologics and prescriber: Patient is not receiving Nucala with other listed biologics; dosing per U.S. FDA labeling; prescribed by allergist/immunologist/otolaryngologist/pulmonologist; initial authorization no more than 12 months

Reauthorization: Documentation of positive clinical response; continue as add-on with intranasal corticosteroids; administration exceptions or patient ≤11 years if applicable; not receiving concomitant biologics; dosing per U.S. FDA labeling; reauthorization no more than 12 months

Exacerbations occurred while receiving maintenance therapy with either triple therapy (LAMA+LABA+ICS) OR dual LAMA+LABA with failure/contraindication/intolerance to an ICS

Concomitant therapy and administration exceptions: Nucala used as add-on maintenance with specified regimens; AND one of administration exceptions (cannot self-administer, documented severe hypersensitivity within 6 months, or new to therapy requiring initial monitored dose)

No concomitant biologics and prescriber: Patient is not receiving Nucala with listed biologics; dosing per U.S. FDA labeling; prescribed by allergist/immunologist/pulmonologist; initial authorization no more than 12 months

Reauthorization: Documentation of positive clinical response; Nucala used in combination with maintenance therapy; administration exception documentation as applicable; not receiving concomitant biologics; dosing per U.S. FDA labeling; reauthorization no more than 12 months

No concurrent biologics: Patient is not receiving Nucala in combination with any of the following for the same indication: anti-IL-5 therapies (e.g., Cinqair, Fasenra), anti-IgE (Xolair), anti-IL-4 (Dupixent), or TSLP inhibitor (Tezspire)

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Dosing and duration: Dosing must be in accordance with FDA approved labeling; reauthorization will be for no more than 12 months

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Based on randomized 32-week trial entry criteria

Chronic rhinosinusitis with nasal polyps (CRSwNP): Add-on maintenance for adults 18+ with inadequate response to nasal corticosteroids and objective polyp burdenadult

Based on 52-week CRSwNP trial requiring NPS and VAS criteria

COPD with eosinophilic phenotype: Add-on maintenance for adult patients with inadequately controlled COPD and an eosinophilic phenotype with prior exacerbations despite triple therapyhistory of >=2 moderate or 1 severe exacerbation in prior year

Reflects MATINEE and METREX trial populations

COPD (baseline pre-treatment)>= 300 cells/µL

HES (baseline pre-treatment for Nucala initial therapy)>= 1,000 cells/µL within the past 4 weeks

inv-31: Blood eosinophil thresholds referenced in trials

Benralizumab pivotal trials (SIROCCO, CALIMA)>= 300 cells/µL entry criterion

Mepolizumab asthma trialsUsed either >=150 cells/µL at screening or >=300 cells/µL within 12 months

Reslizumab pivotal asthma studies>= 400 cells/µL entry criterion in Studies I-II

inv-32: HES diagnostic eosinophil level

Typical diagnostic level cited for HES>1,500 eosinophils/µL sustained

HES trial entry requirement (mepolizumab randomized trial)>= 1,000 cells/µL at screening

Required duration for typical HES definitionSustained for >= 6 months

inv-33: blood eosinophil thresholds — examples from trials and guidance

Reslizumab (Cinqair) pivotal asthma trials example>= 400 cells/µL entry criterion

Mepolizumab HES randomized trial screening threshold>= 1,000 cells/µL

ERS/ATS guidance exampleSuggests a blood eosinophil cut-point >=150 µL^-1 to guide anti-IL-5 initiation in adults with severe asthma

inv-34: HES duration (diagnostic/supporting timeframe)

Typical HES duration for diagnostic consideration>= 6 months

Clinical trial requirement (mepolizumab HES program)Trials excluded secondary causes; treatment trials required recent flares and screening eosinophils >=1,000 cells/µL

Policy HES duration requirement for Nucala indication>= 6 months without identifiable non-hematologic secondary cause

Prior Authorization

Indication-specific prior authorization

Prior authorization requests must meet the indication-specific requirements (e.g., reslizumab for add‑on maintenance severe eosinophilic asthma in adults with documented eosinophilia and prior controller therapy; mepolizumab and benralizumab criteria vary by indication and age).

Prior Authorization

Prior authorization for biologics

Prior authorization must align with FDA-indicated uses and UnitedHealthcare criteria for biologic therapies; the policy requires PA for these agents and was updated on 04/01/2026.

Step Therapy

Step through anti-IL-5 agents before Cinqair

Cinqair (reslizumab) requires prior trial failure of an anti‑IL‑5 agent: history of failure of a 4‑month trial of Fasenra or Nucala, or documented contraindication/intolerance to those agents, before approval.

Step Therapy

Add-on and prior therapy requirements

Therapy must be used as add‑on to specified controller regimens (examples: maximally‑dosed ICS/LABA combinations for asthma; intranasal corticosteroids for CRSwNP; specified maintenance regimens for COPD) and after trials/failure of specified therapies where stated.

Denial Risk

Prohibition on combination biologic therapy

The patient must not be receiving the requested agent in combination with other listed biologic therapies (anti‑IL‑5 agents, anti‑IgE, anti‑IL‑4, or TSLP inhibitors) for the same indication.

Note

Biologic add-on sequencing per GINA

Guideline-based sequencing: biologic add‑on therapy is recommended for uncontrolled severe asthma despite optimized maximal therapy; selection among biologics depends on phenotype (e.g., anti‑IL‑5/5R for eosinophilic asthma).

Step Therapy

Step therapy (not specified in excerpt)

No additional step therapy specifics are provided in this excerpt; operational template update noted without new step requirements.

Documentation Required

Reauthorization response documentation

For reauthorization, submit documentation demonstrating positive clinical response such as reduced relapse frequency/severity, steroid dose reduction/discontinuation, disease remission, or reduction in EGPA-related symptoms.

Documentation Required

Baseline eosinophil documentation

Document baseline peripheral blood eosinophil level (pre-treatment) demonstrating ≥150 cells/µL for eosinophilic asthma indications prior to initiation.

Documentation Required

HES baseline labs and therapy documentation

For HES initial therapy, submit medical records documenting baseline blood eosinophil level ≥1,000 cells/µL within the past 4 weeks and documentation of stable background HES therapy.

Documentation Required

Diagnosis and disease control documentation

Provide documentation supporting the diagnosis and evidence of uncontrolled disease or exacerbations, the eosinophilic phenotype (e.g., baseline peripheral blood eosinophil level), and prior controller therapies or surgeries as specified per indication.

Documentation Required

Reauthorization documentation

For reauthorization of Nucala, document positive clinical response and that Nucala is used in combination with maintenance inhaled therapy as specified; attest administration exception if applicable.

Documentation Required

Administration competency or hypersensitivity documentation

If the patient or caregiver cannot self‑administer Fasenra or Nucala, provide physician attestation; alternatively, document recent severe hypersensitivity requiring administration and direct monitoring by a healthcare professional.

Documentation Required

CRSwNP baseline documentation

For CRSwNP, document prior nasal corticosteroid use (≥8 weeks), history of prior nasal polypectomy where applicable, and baseline nasal obstruction VAS and endoscopic nasal polyp scores as reflected in trial entry criteria.

Documentation Required

Eosinophil counts and exacerbation history

Include blood eosinophil counts and prior exacerbation history (examples: ≥400/µL in reslizumab asthma trials; ≥1 exacerbation requiring systemic corticosteroid in prior 12 months in reslizumab studies; ≥1,000 cells/µL screening threshold used in HES trial) as relevant to the indication.

Documentation Required

Indication and age documentation

Prescribing must document the specific FDA‑approved indication and patient age where required (e.g., reslizumab adults 18+, mepolizumab and benralizumab age limits per label).

Denial Risk

Insufficient evidence of uncontrolled asthma

Cinqair or Fasenra requests may be denied if asthma is not documented as uncontrolled/inadequately controlled by the policy definitions (no poor symptom control, no qualifying corticosteroid bursts, no exacerbation history, no airflow limitation, or not OCS‑dependent).

Denial Risk

Insufficient EGPA diagnostic documentation

Requests for Fasenra or Nucala for EGPA may be denied if documentation does not support relapsing or refractory EGPA and the required characteristic features (diagnosis, asthma history, and at least two typical EGPA features).

Denial Risk

Dosing, prescriber specialty, and duration requirements

Requests may be denied if dosing is not in accordance with FDA‑approved labeling, if prescribed by a non‑specified specialty, or if initial authorization exceeds the stated limits (typically no more than 12 months; Nucala for EGPA initial auth ≤6 months).

Denial Risk

Not medically necessary for COPD (Cinqair, Fasenra)

Use of Cinqair or Fasenra for COPD is considered unproven and not medically necessary and may be denied when submitted for that indication.

Denial Risk

Anaphylaxis risk on administration

Because reslizumab carries a risk of anaphylaxis, providers administering Cinqair must observe patients closely after infusion and be prepared to manage anaphylaxis.

Denial Risk

Off-label or non-indicated uses

Use of Fasenra or Nucala for indications outside their FDA‑approved indications (such as other eosinophilic conditions not listed, acute bronchospasm, or status asthmaticus) is considered unproven/not covered and may be denied.

Relapsing or refractory disease definitionRelapsing disease: >=1 relapse within 2 years requiring escalation or hospitalization; Refractory: failure to attain remission within 6 months of induction therapy

inv-63: Eosinophilic phenotype — definition by indication

Asthma eosinophilic phenotype cutoff>= 150 cells/µL (baseline pre-treatment)

COPD eosinophilic phenotype cutoff>= 300 cells/µL (baseline pre-treatment)

HES pre-treatment threshold (policy)>= 1,000 cells/µL (within past 4 weeks)

inv-64: CRSwNP diagnosis criteria

Required symptom durationTwo or more symptoms for >12 weeks (e.g., nasal discharge, obstruction, facial pain, loss of smell)

Objective findingsEndoscopic or CT evidence: purulent mucus/edema in middle meatus or ethmoid; polyps in nasal cavity or middle meatus; CT mucosal thickening/opacification

Polyp history/prior surgeryBilateral nasal polyposis or prior bilateral nasal polypectomy; prior sinus surgery or systemic corticosteroids in prior 2 years considered

inv-65: Hypereosinophilic Syndrome (HES)

Core definitionDisorder with sustained overproduction of eosinophils associated with organ damage

Typical blood eosinophil level>1,500 eosinophils/µL for >= 6 months

Trial-related screening criterion>= 1,000 cells/µL at screening for randomized HES trial

inv-66: EGPA (Eosinophilic Granulomatosis with Polyangiitis)

Core featuresVasculitis characterized by asthma, sinusitis, pulmonary infiltrates, neuropathy, and eosinophilic vasculitis affecting end organs

Standard therapySystemic glucocorticoids are standard treatment; some patients are relapsing or refractory

EGPA treatment indicationBenralizumab and mepolizumab indicated for adult EGPA per FDA labeling (policy aligns with FDA indications)

inv-67: Uncontrolled asthma

Definition (clinical)Asthma with poor symptom control and/or frequent exacerbations (>=2/year requiring OCS or >=1/year requiring hospitalization)

Measures includedSymptom control scores (ACQ/ACT), exacerbation history, airflow limitation, OCS dependence

Use for treatment selectionUsed to determine eligibility for add-on biologic therapy per guideline recommendations (GINA)

inv-68: Difficult-to-treat asthma

DefinitionAsthma uncontrolled despite medium- or high-dose ICS plus a second controller or maintenance OCS, or that requires high-dose treatment to maintain control

ImplicationRepresents population for whom biologic add-on therapy may be considered after optimizing adherence and contributory factors

Distinction from severe asthmaDifficult-to-treat refers to nonresponse due to factors like adherence or comorbidity versus true severe asthma

inv-69: Severe asthma

DefinitionAsthma uncontrolled despite optimized high-dose ICS-LABA and management of contributory factors, or that worsens when high-dose treatment decreased

Treatment implicationSevere asthma population eligible for add-on biologics per FDA-indicated ages and phenotype

Age considerationFasenra and Nucala indicated for patients aged >=6 years for severe asthma per FDA

inv-70: EGPA — indicated treatment population note

Indicated population noteEGPA coverage limited to relapsing or refractory disease with required characteristic features and concurrent standard therapy

Administration considerationsProvider administration justification allowed for initial monitored dose or hypersensitivity or inability to self-administer

Prescriber specialty and durationDosing per FDA labeling; prescribed by specified specialists; initial authorization time-limited per indication (e.g., Nucala EGPA ≤6 months)

inv-71: HES — indicated patient age and duration

Indicated patient age for mepolizumab in HESPatients aged >=12 years

Required duration prior to labeling consideration>= 6 months of HES without identifiable non-hematologic secondary cause

Baseline lab requirement for initial therapy>= 1,000 cells/µL within the past 4 weeks and stable background HES therapy

inv-72: CRSwNP — indicated age and role

Indicated age for mepolizumab in CRSwNPAdults 18 years and older

Role of therapyAdd-on maintenance treatment for patients with objective polyp burden and inadequate response to intranasal corticosteroids

Documentation standardsTrial-based benchmarks include prior nasal corticosteroid use >= 8 weeks, prior polypectomy history, and baseline NPS/VAS scores