ModifiedPremera BluecrossPolicy N/A

IL-5 Inhibitors (Cinqair, Fasenra, Nucala) - Coverage Criteria

Defines medical necessity, site-of-service review, and coverage criteria for Cinqair (reslizumab), Fasenra (benralizumab), and Nucala (mepolizumab) for eosinophilic asthma and other labeled eosinophilic indications; applies to Premera members (with an Alaska fully-insured exception for site-of-service rules).

Policy Summary

PayerPremera Bluecross

PolicyIL-5 Inhibitors (Cinqair, Fasenra, Nucala) - Coverage Criteria

Policy CodePolicy N/A

Change TypeMaterial updates to age limits, eosinophil thresholds, site-of-service rules, and combination-therapy prohibitions

Effective DateFeb 1, 2026

Next Review DateJan 13, 2026

Key ActionSubmit prior authorization with office visit notes, eosinophil lab results, and documentation of prior inhaled corticosteroid+LABA use to support medical necessity.

SourceLink

POLICY UPDATE CHANGES

Updated Fasenra age requirement from 12 years or older to 6 years or older.

Added explicit prohibitions on combination use of listed biologics (Xolair, Dupixent, Tezspire, and other IL-5 inhibitors) for treatment of asthma and nasal polyps.

Changed eosinophil threshold in asthma criteria multiple times: 150 → 300 cells/µL (effective Jan 3, 2025), then back to 150 cells/µL (updated Feb 1, 2025).

Added site-of-service review/requirements for Fasenra and Nucala and clarified that site-of-service criteria do not apply to Alaska fully-insured members per Alaska HB 226.

Updated asthma diagnostic criteria to require exacerbation history or FEV1 <80% predicted or FEV1/FVC <0.80 with worsening on steroid taper.

Added prescriber requirement for Nucala (and for Fasenra and Cinqair in some asthma indications).

Updated Nucala coverage to include certain COPD patients and adjusted nasal polyps criteria (removed requirement for surgery within last 10 years; require prior systemic steroids or prior bilateral polyp surgery).

Updated EGPA eosinophil threshold for Fasenra and Nucala from ≥1500 cells/µL to ≥1000 cells/µL.

Nucala CRSwNP criteria updated to prohibit combination use with Tezspire (tezepelumab-ekko).

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

3drugs covered (Cinqair, Fasenra, Nucala)

12max approval period (months)

150current asthma eosinophil threshold

6Fasenra minimum age

HB 226Alaska SOS exception

Coverage Criteria and Medical Necessity

Initial Therapy - Cinqair (reslizumab)

Cinqair (reslizumab) — covered when ALL of the following are met

Cinqair initial therapy: Individual aged ≥18 yearsage >= 18

Baseline therapy: Using maximum tolerated doses of an inhaled corticosteroid AND an inhaled long‑acting beta‑agonist (LABA)

Asthma severity: One of: 2 or more asthma exacerbations in the previous 12 months requiring oral/systemic corticosteroids OR 1 or more exacerbations requiring hospitalization, emergency department, or urgent care in the previous 12 months OR FEV1 <80% predicted OR FEV1/FVC <0.80 OR asthma worsens on tapering of oral corticosteroid therapy

Eosinophilic evidence: One of: blood eosinophil count ≥ 150 cells/mcL OR sputum eosinophils ≥ 3% OR oral/systemic corticosteroid–dependent asthma in which the patient is unable to discontinue corticosteroids for testingeosinophils >=150 cells/mcL or sputum >=3%

Other restrictions: Not used in combination with specified biologics for asthma; prescribed by or in consultation with an allergist/immunologist or pulmonologist; maintenance dose limited to 3 mg/kg every 4 weeksdose limit

Initial Therapy - Fasenra (benralizumab)

Fasenra (benralizumab) — covered when ALL of the following are met

Fasenra initial therapy: Individual aged ≥6 yearsage >= 6

Baseline therapy: Using maximum tolerated doses of an inhaled corticosteroid AND an inhaled long‑acting beta‑agonist (LABA)

Initial Therapy - Nucala (mepolizumab) and other labeled indications

Nucala (mepolizumab) — covered when ALL of the following are met (by indication)

Asthma indication: Individual aged ≥6 years; using maximum tolerated doses of an inhaled corticosteroid AND an inhaled LABA; meets asthma severity criteria (2 or more exacerbations requiring systemic corticosteroids OR 1 or more exacerbation requiring hospitalization/ED/urgent care OR FEV1 <80% predicted OR FEV1/FVC <0.80 OR asthma worsens on tapering oral corticosteroids); AND has at least one eosinophil criterion (blood eosinophils ≥ 150 cells/mcL OR sputum eosinophils ≥ 3% OR oral/systemic corticosteroid–dependent asthma unable to discontinue)

Asthma other restrictions: Not used in combination with specified biologics for asthma; prescribed by or in consultation with an allergist/immunologist or pulmonologist; maintenance dose limited to 100 mg every 4 weeksdose limit

COPD indication: Individual aged ≥18 years with inadequately controlled COPD and blood eosinophils ≥ 150 cells/mcL within the prior 12 months; trial of LAMA/LABA ≥ 90 days unless not tolerated; and 2 or more exacerbations requiring systemic steroids/antibiotics OR 1 or more hospitalization in prior 12 months; prescribed by or in consultation with an allergist/immunologist or pulmonologist

Continuation / Reauthorization Criteria

Re-authorization / Continuation

Reauthorization general: May be approved up to 12 months if medical necessity criteria are met and chart notes document continued positive clinical responseup to 12 months

Evidence of response for asthma/COPD/EGPA: Any of: decrease in oral steroid requirement, decrease in exacerbation frequency, fewer ER/urgent care visits or hospitalizations OR decrease in frequency/severity of symptoms OR increase in quality-of-life and ability to perform activities of daily living

Evidence of response for HES: Decrease in number or severity of HES flares from baseline

Evidence of response for CRSwNP: Decrease from baseline in nasal polyp size AND improvement in nasal congestion score or documented decrease from baseline of nasal congestion

Covered indications and trial-derived criteria

Evidence-supported indications and trial-derived criteria referenced in the policy (summarized from clinical trials and indications):

CRSwNP - Nucala (mepolizumab): Adults with CRSwNP with recurrent symptomatic polyps who received background nasal corticosteroids >=8 weeks prior, VAS nasal obstruction >5/10, and endoscopic bilateral nasal polyp score (NPS) >=5 with >=2 in each cavity; NUCALA 100 mg SC q4 weeks showed significant improvement vs placebo in SYNAPSENPS >=5; VAS >5; background nasal steroid >=8 weeks

derived from SYNAPSE trial

Severe eosinophilic asthma - mepolizumab: Individuals with severe eosinophilic asthma (e.g., blood eosinophils >=300 cells/mcL in primary analyses) uncontrolled on high‑dose ICS plus other controllers had significant reductions in exacerbation rates with mepolizumab (DREAM, MENSA)>=300 cells/mcL primary; some trials included >=150 cells/mcL

DREAM and MENSA trials summarized

COPD with eosinophilic phenotype - mepolizumab:

Benralizumab (Fasenra) — evidence-based coverage group

Coverage considerations supported by trial evidence

Benralizumab efficacy group: Benefits demonstrated in adults with uncontrolled asthma on ICS/LABA with baseline eosinophils >=300 cells/μL (primary) and evidence of benefit in post‑hoc analyses at >=150 cells/μL — reductions in exacerbation rates and improvements in FEV1; ZONA trial showed oral corticosteroid‑sparing in patients with >=150 cells/μLbaseline eosinophils >=150 or >=300 cells/μL

Reslizumab (Cinqair) — evidence-based coverage group

Coverage considerations supported by reslizumab trial evidence

Reslizumab efficacy and safety: Reslizumab 3 mg/kg reduced exacerbation rate by ~50% and improved FEV1 in adults with eosinophilic asthma in pivotal trials (studies 3082/3083); safety signals include treatment‑related anaphylaxis and rare creatine phosphokinase (CPK) elevations; efficacy in adolescents was not established

Initial therapy / general asthma criteria

Covered when ALL of the following are met (summary of updated asthma diagnostic and eosinophil criteria):

Asthma severity and phenotype: Individual meets asthma diagnostic criteria: 2 or more exacerbations in prior 12 months requiring oral corticosteroids OR 1 or more exacerbations requiring hospitalization/ED/urgent care OR FEV1 <80% predicted OR FEV1/FVC <0.80 with asthma that worsens on tapering oral corticosteroidssee text

Eosinophil count: Blood eosinophil count >=150 cells/mcL within the last 12 months (policy history documents interim changes to 300 cells/mcL with subsequent reversion to 150 cells/mcL)150 cells/mcL

Prior/concomitant therapy: Using maximum tolerated doses of inhaled corticosteroid therapy and prior systemic corticosteroids or prior surgical history for nasal polyps where applicable; for OCS‑dependent asthma document inability to discontinue OCS for testingmaximum tolerated

Site-of-service and authorization

Site-of-service and duration criteria

Site-of-service review: Site-of-service medical necessity review may apply to infusion or injection drugs (site‑of‑service review added/clarified for Fasenra and Nucala); exception for Alaska fully‑insured members per Alaska HB 226; non‑formulary exception authorizations may be approved up to 12 monthsn/a

Nucala additional indications

Nucala-specific additional coverage additions

Additional indications: Nucala coverage expanded to include certain individuals with COPD; nasal polyps criteria updated to require prior use of systemic corticosteroids in the last 2 years OR prior bilateral nasal polyp surgery (removed prior 10‑year surgery requirement)n/a

Coverage-impacting historical revisions

Summary of coverage-impacting changes recorded in the policy history that affect medical necessity criteria

eosinophil_threshold_changes: Eosinophil thresholds for asthma coverage were changed multiple times between 150 and 300 cells/mcL; current policy permits >=150 cells/mcL with allowances for exceptions when individuals cannot discontinue corticosteroids for testing>=150 cells/mcL

prescriber_and_age_requirements: Prescriber requirements were added for certain agents and indications; Fasenra age eligibility was lowered to 6 yearsage >=6 for Fasenra

site_of_service_rule: Site‑of‑service medical necessity review was added or clarified for infusion and injection drugs for specific agents; Alaska fully‑insured members are excepted from site‑of‑service medical necessity per Alaska HB 226N/A

All uses of Cinqair (reslizumab), Fasenra (benralizumab), and Nucala (mepolizumab) that are not specifically described in this policy are considered investigational and may be denied. This includes off‑label indications or other eosinophilic conditions not listed in the policy statements.

Benefit application varies by product: Cinqair (reslizumab) is managed under the medical benefit only, while Fasenra (benralizumab) and Nucala (mepolizumab) may be managed under either the pharmacy or medical benefit depending on how they are billed. Prior authorization is required for injectable IL‑5 agents billed under HCPCS codes (e.g., J0517, J2182, J2786).

Pooled trial and advisory-panel data did not demonstrate consistent benefit for reslizumab (Cinqair) in adolescents (age 12–17); an advisory review noted efficacy was established in adults but not in this adolescent subgroup. Safety signals specific to reslizumab (including treatment‑related anaphylaxis and rare creatine phosphokinase elevations) further inform scrutiny of requests in younger populations.

The agents listed in this policy (including omalizumab, dupilumab, tezepelumab, and the IL‑5 inhibitors) are not to be used in combination for the treatment of the same indication. Concurrent use of two or more of these biologic therapies is prohibited by the policy due to limited evidence supporting safety and additive benefit.

For chronic rhinosinusitis with nasal polyps (CRSwNP), Nucala (mepolizumab) must not be used in combination with Tezspire (tezepelumab‑ekko). The policy explicitly prohibits this combination when both agents are directed at the treatment of CRSwNP.

The policy’s prohibition on combination biologic use applies across indications: requests to combine an IL‑5 inhibitor with other specified biologics for asthma, COPD, EGPA, or CRSwNP will not meet medical necessity. This restriction was added and clarified in recent updates and is enforced for the listed agents.

Site‑of‑service medical necessity review is limited for pediatric individuals younger than 13 years. The policy restricts site‑of‑service review (infusion/administration location determination) to individuals aged 13 years or older, reflecting pediatric considerations in infusion care.

Combination biologic therapy (concurrent administration of two of the named biologic agents) is not supported for the treatment of asthma or nasal polyps and may be denied. Nucala, Fasenra, and Cinqair must not be combined with other listed biologics when used for these indications.

Policy history records the addition of the combination‑use prohibition; operationally, this means requests for concurrent biologic therapy among the listed agents will be reviewed and are expected to be processed as not meeting medical necessity under current policy language.

Billing Codes, Doses, and Clinical Thresholds

Covered biologic productsmixedCovered

Cinqair (reslizumab)	product listed — IV, managed under medical benefit
Fasenra (benralizumab)	product listed — SC, managed under pharmacy and medical benefit
Nucala (mepolizumab)	product listed — SC, managed under pharmacy and medical benefit

HCPCS codes for IL-5 agentsHCPCSCovered

J0517	Injection, benralizumab (Fasenra) 1 mg
J2182	Injection, mepolizumab (Nucala) 1 mg
J2786	Injection, reslizumab (Cinqair) 1 mg

Policy historical/used HCPCS codesHCPCS

J2786	Cinqair (reslizumab) HCPCS code referenced in history
J0517	HCPCS code added 01/01/19 (history entry)
J2182	HCPCS code added 01/01/17 (history entry)

inv-24: Blood eosinophil — common thresholds and indication-specific values

Common asthma thresholdBlood eosinophils >=150 cells/mcL (policy common requirement for asthma indications)

Trial primary threshold>=300 cells/mcL (used as primary analysis population in pivotal benralizumab and mepolizumab trials)

Sputum thresholdSputum eosinophils >=3% (alternative eosinophilic phenotype marker)

EGPA/HES higher thresholdsEGPA: absolute or percent thresholds used (policy references ≥1000 cells/mcL or ≥10%); HES: ≥1000 cells/mcL

Timeframe for measurementEosinophil count within the last 12 months is acceptable for asthma criteria

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required and Benefit Application

Prior authorization is required for Nucala (mepolizumab), Fasenra (benralizumab), and Cinqair (reslizumab) when billed under the medical or pharmacy benefit as indicated. Site-of-service review may apply for infusion/injection administrations; Alaska fully‑insured members are exempt from SOS rules per Alaska HB 226. Non‑formulary exception authorizations may be approved up to 12 months.

Cinqair (reslizumab) — managed under medical benefit; subject to SOS review
Nucala (mepolizumab) — managed under pharmacy and medical benefits; subject to SOS review
Fasenra (benralizumab) — managed under pharmacy and medical benefits; subject to SOS review
Site-of‑Service rules do not apply to Alaska fully‑insured members (Alaska HB 226)

Prior Authorization

Prior Authorization Based on Eosinophil Threshold and Prior Therapy

Approvals for asthma indications include eosinophil and prior‑therapy thresholds. Current criteria require documented blood eosinophil counts within the stated timeframe and evidence of prior controller therapy and exacerbation history as specified for each product.

Clinical Background and Mechanism

Eosinophils are circulating white blood cells that participate in type‑2 inflammatory responses and contribute to airway inflammation in eosinophilic asthma. IL‑5 is a central cytokine for eosinophil growth, activation, and survival. Monoclonal antibodies that target the IL‑5 pathway act by either binding IL‑5 (e.g., reslizumab, mepolizumab) or the IL‑5 receptor alpha (e.g., benralizumab), resulting in decreased eosinophil counts and reduced eosinophil‑mediated inflammation; these agents are used as add‑on therapies to reduce exacerbations in appropriately selected patients.

Key Definitions and Terms

inv-55: Eosinophil count — definition and common thresholds

DefinitionEosinophil count: a blood (or sputum) test measuring eosinophil levels; used to identify eosinophilic phenotype (e.g., blood >=150 cells/mcL or sputum >=3%)

Clinical significanceElevated eosinophils indicate eosinophilic inflammation associated with severe asthma and guide IL-5 inhibitor use

Measurement timeframePolicy accepts blood eosinophil measurements within the last 12 months for asthma criteria

inv-56: Site of service (SOS) — definition and examples

DefinitionSite of service (SOS): location where the drug is administered (hospital outpatient, infusion center, physician office, or home)

Policy applicationSOS medical necessity review applies only to medical benefit reviews and is not applied to Alaska fully-insured members per policy

Policy Revision History and Material Changes

2024-06-01age_change

Fasenra (benralizumab) minimum age lowered from 12 years to 6 years.

2024-07-01combination_therapy_prohibition

Policy clarified that listed biologics (including Xolair, Dupixent, Tezspire, Cinqair, Fasenra, and Nucala) are not to be used in combination for treatment of asthma and nasal polyps.

2025-01-03eosinophil_threshold_increase

Policy Summary

PayerPremera Bluecross

PolicyIL-5 Inhibitors (Cinqair, Fasenra, Nucala) - Coverage Criteria

Policy CodePolicy N/A

Change TypeMaterial updates to age limits, eosinophil thresholds, site-of-service rules, and combination-therapy prohibitions

Effective DateFeb 1, 2026

Next Review DateJan 13, 2026

Key ActionSubmit prior authorization with office visit notes, eosinophil lab results, and documentation of prior inhaled corticosteroid+LABA use to support medical necessity.

SourceLink

On This Page

eosinophils >=150 cells/mcL or sputum >=3%

eosinophils >=150 cells/mcL; LAMA/LABA >=90 days

EGPA indication: Individual aged ≥18 years with history or presence of asthma; stable prednisone/prednisolone dose 7.5–50 mg with/without immunosuppressives; blood eosinophils >=10% OR absolute >=1000 cells/mcL; and at least one vasculitis criterion (biopsy or supported findings); prescribed by or in consultation with allergist/immunologist, pulmonologist, or rheumatologist; dose limited to 300 mg every 4 weekseosinophils >=10% or >=1000 cells/mcL

HES indication: Individual aged ≥12 years with documented history >=6 months without secondary cause; FIP1L1-PDGFRA negative; blood eosinophils >=1000 cells/mcL; >=2 HES flares in prior 12 months requiring escalation; receiving background HES therapy >=4 weeks; prescribed by or in consultation with a hematologist; dose limited to 300 mg every 4 weekseosinophils >=1000 cells/mcL; duration >=6 months

CRSwNP indication: Individual aged ≥18 years with inadequately controlled bilateral CRSwNP; at least 2 symptoms including nasal congestion/loss of smell/facial pressure; failed intranasal corticosteroid monotherapy; Nucala prescribed with intranasal corticosteroid; prior systemic corticosteroids for polyps in last 2 years OR prior bilateral nasal polyp surgery; dose 100 mg every 4 weeks; not used in combination with specified biologics for CRSwNPdose limit

Phase 3 MATINEE and METREX trials showed a statistically significant reduction in annualized moderate/severe exacerbation rate when Nucala was added to triple inhaled therapy in eosinophilic COPD phenotype

eosinophilic phenotype as defined in trials

MATINEE and METREX summarized

Benralizumab efficacy criteria: Adults with uncontrolled asthma on high‑dose ICS/LABA and baseline eosinophils >=300 cells/mcL (primary) showed reduced exacerbation rates in CALIMA and SIROCCO trials with benralizumab (30 mg SC regimens)>=300 cells/mcL primary analysis

CALIMA and SIROCCO summarized

Prescriber requirement: Certain indications require a specified prescriber (updated for Nucala and added for Fasenra and Cinqair in asthma/EGPA)n/a

combination_use_prohibition: Policy clarifies listed biologics (e.g., Nucala, Fasenra, Cinqair, Dupixent, Tezspire, Xolair) are not to be used in combination for treatment of asthma or nasal polypsN/A

inv-25: Maintenance dosing limits — typical dosing schedules by agent

Cinqair (reslizumab)3 mg/kg IV every 4 weeks (dose limit per policy)

Fasenra (benralizumab)30 mg subcutaneously: initial dosing then maintenance every 8 weeks (per trial/regimen described; 30 mg q8w maintenance)

Nucala (mepolizumab)100 mg subcutaneously every 4 weeks (standard maintenance dose; higher dosing for some indications up to 300 mg q4w per labeling/policy)

inv-26: Blood eosinophil count — primary trial analysis threshold (>= 300 cells/mcL)

Primary trial analysis threshold>= 300 cells/mcL (primary analysis population used in pivotal CALIMA/SIROCCO and key mepolizumab trials)

Trial subgroup usageTrials reported efficacy by baseline eosinophil strata (<150, 150–299, >=300) with primary focus on >=300 cells/mcL

Supporting trial referencesCALIMA, SIROCCO, DREAM, MENSA referenced as using >=300 cells/mcL as primary or key efficacy subgroup

inv-27: Baseline blood eosinophil count — common and post-hoc thresholds (>=150 and >=300)

Common baseline threshold (post-hoc)>=150 cells/µL (post-hoc subgroups showed benefit; used in pooled benralizumab analyses)

Primary analysis threshold>=300 cells/µL (primary trial analysis for pivotal benralizumab and mepolizumab trials)

Stratified trial reportingTrials reported efficacy across multiple baseline eosinophil strata including <150, 150–299, and >=300 cells/µL

inv-28: Oral prednisone — clinical endpoint reference (e.g., reduction to <5 mg/day)

Clinical endpoint referencedReduction in oral prednisone to physiologic levels (<5 mg/day) was an endpoint in the ZONA trial for benralizumab

OCS-sparing outcomeZONA demonstrated statistically significant reductions in oral corticosteroid requirements versus placebo

Trial population requirementZONA enrolled adults with minimum blood eosinophil count >=150 cells/µL on stable prednisone prior to enrollment

inv-29: Blood eosinophil count — current policy threshold history (150 cells/mcL; changed 150100300150)

Current policy threshold historyPolicy established eosinophil requirement at 150 cells/mcL (within last 12 months) as of Feb 1, 2025 after interim changes

Interim change to 300Eosinophil threshold was updated to 300 cells/mcL effective Jan 3, 2025 (later reverted)

Reversion noteThreshold reverted from 300 cells/mcL back to 150 cells/mcL on Feb 1, 2025 per policy history

inv-30: FEV1 — lung-function diagnostic threshold (<80% predicted)

FEV1 diagnostic thresholdFEV1 <80% predicted is one of the diagnostic criteria options for severe asthma in the policy

Role in criteriaFEV1 <80% predicted can satisfy the asthma severity requirement when paired with other baseline therapy requirements

Trial/lab documentationFEV1 values are accepted documentation to support medical necessity and reauthorization assessments

inv-31: FEV1/FVC — lung-function diagnostic threshold (<0.80 with steroid-taper worsening)

FEV1/FVC diagnostic thresholdFEV1/FVC <0.80 is an accepted diagnostic criterion when asthma worsens upon tapering oral corticosteroids

Context of useFEV1/FVC <0.80 is used alongside clinical worsening on steroid taper to meet asthma severity criteria

Policy historyFEV1/FVC <0.80 was added to asthma coverage criteria in 2025 updates

inv-32: Eosinophil count — documented threshold changes and EGPA revision (150/300 and EGPA 15001000)

EGPA threshold revisionEGPA absolute eosinophil count requirement was revised from >=1500 cells/µL to >=1000 cells/µL

inv-33: Age — Fasenra minimum age lowered to 6 years

Fasenra minimum ageFasenra (benralizumab) age eligibility lowered to 6 years (policy update effective 06/01/24)

Age across agentsPolicy age requirements vary by drug and indication; see specific drug criteria for exact minimum ages

Asthma eosinophil threshold: policy updates have varied (150 vs 300 cells/µL historically); verify effective criteria at time of request — recent revisions allow ≥150 cells/µL within the last 12 months in some updates
Baseline therapy requirement: documentation of use of maximum tolerated inhaled corticosteroid AND an inhaled long‑acting beta‑agonist (LABA) is required
Exacerbation/prior‑therapy evidence: ≥2 exacerbations requiring systemic/oral corticosteroids in prior 12 months, or ≥1 exacerbation requiring hospitalization/ED/urgent care, or FEV1 <80% predicted, or FEV1/FVC <0.80, or asthma that worsens when tapering oral corticosteroids

Denial Risk

Safety and Subgroup Concerns May Trigger Coverage Scrutiny

Safety signals and subgroup effects are considered during review. Requests may receive intensified scrutiny for agents with known serious adverse events or subgroup‑specific efficacy concerns.

Reslizumab (Cinqair) safety signals: anaphylaxis and elevated CPK (muscle toxicity) reported in trials — monitor and document prior reactions
Benralizumab (Fasenra) safety: long‑term trial data include SAEs and antibody responses; document relevant safety history and monitoring plans
Document any history of hypersensitivity, prior malignancy concerns, CPK elevations, or other significant adverse events

Denial Risk

Combination Therapy Prohibition

Combination biologic therapy for the same indication is prohibited. Requests to use two or more of the listed monoclonal antibodies concurrently for asthma, CRSwNP, EGPA, HES, or other covered indications will be denied.

Prohibited combinations include co‑administration of: Xolair (omalizumab), Dupixent (dupilumab), Tezspire (tezepelumab‑ekko), Cinqair (reslizumab), Fasenra (benralizumab), and Nucala (mepolizumab) for the same treated condition
Nucala for CRSwNP must not be used in combination with Dupixent or Xolair

Denial Risk

Triggers for Denial (Historical Revisions)

Requests lacking required documentation or not meeting updated criteria may be denied. Historical policy revisions have changed eosinophil thresholds, prescriber requirements, age limits, SOS applicability, and background therapy language — ensure the submitted documentation matches the effective criteria date.

Common triggers for denial: eosinophil value outside required timeframe or below the threshold in effect for the service date
Prescriber requirement not met for certain indications (some updates require allergist/immunologist, pulmonologist, or rheumatologist)
Age criteria not met (e.g., Fasenra age lowered to ≥6 years in 2024 update — confirm current age requirement)
Requests that do not follow SOS rules when applicable (except Alaska fully‑insured members)

Documentation Required

Required Documentation

Submit office visit notes and objective data to support medical necessity. Incomplete or missing documentation (office notes, labs, medication history) may result in denial or delay.

Office visit notes including diagnosis, relevant history, physical exam, and medication history are required
Laboratory values: most recent blood eosinophil count with date (within timeframe required by policy); if on systemic corticosteroids and eosinophil testing cannot be performed, document inability to discontinue and rationale
Pulmonary function data if used to meet criteria (FEV1, FEV1/FVC)

Documentation Required

Required Clinical Documentation to Support Medical Necessity

Provide specific clinical data to demonstrate medical necessity: eosinophil counts, exacerbation history, steroid exposure, prior surgical history for CRSwNP, and prescriber specialty when required.

Eosinophil documentation: absolute count (cells/µL) with collection date; policy timeframes have changed — include date to confirm eligibility
Exacerbation evidence: documentation of number and severity of exacerbations in prior 12 months (OCS bursts, ED visits, hospitalizations)
Oral/systemic corticosteroid use: dose and duration (e.g., chronic OCS dose for OCS‑dependent asthma or prior OCS courses)
CRSwNP specifics: symptoms, prior intranasal corticosteroid trial, prior systemic steroid use for nasal polyps within last 2 years or prior bilateral polyp surgery
Pulmonary function testing: FEV1 values and FEV1/FVC ratio where used to meet criteria
Prescriber requirement: note specialist consultation or prescription by a required specialty when applicable

Prior Authorization

Documentation and Prescribing Guidance

Follow FDA dosing and administration. Quantity limits per product labeling apply. Non‑formulary exception approvals may be granted up to 12 months. Confirm the product's current PI for dosing; requests inconsistent with labeled dosing or lacking prescriber rationale may be denied.

Adhere to FDA‑approved dose and frequency and indicate the prescribed dose on the request
Quantity limits added per prescribing information for each product must be observed
Non‑formulary exception reviews: may approve up to 12 months — include clinical rationale for exception requests

Step Therapy

Baseline Therapy Requirement and Step Therapy Position

Positioning in treatment pathway: IL‑5 inhibitors are step‑5 add‑on agents per GINA 2024 and are intended for individuals uncontrolled on optimized background therapy. Ensure prior controller therapy and step‑therapy context are documented.

Baseline therapy requirement: evidence patient is on maximum tolerated inhaled corticosteroid plus a LABA prior to initiating IL‑5 inhibitor therapy
Step therapy context: IL‑5 agents serve as step‑5 add‑on biologic therapy for severe asthma uncontrolled on standard options (ICS/LABA, leukotriene modifiers, etc.)
Document prior alternative therapies attempted and reason for failure or intolerance

Age applicabilityFor members age 13 and older the site-of-service review may be applied per the policy

inv-57: IL05 inhibitors / IL05 pathway agents — drug class definition

DefinitionIL-5 inhibitors / IL-5 pathway agents: monoclonal antibodies targeting IL-5 or the IL-5 receptor to reduce eosinophil activity

MechanismsMepolizumab and reslizumab bind IL-5; benralizumab binds IL-5 receptor alpha leading to eosinophil depletion

Clinical roleUsed as add-on therapies to reduce exacerbations in severe eosinophilic asthma

inv-58: Fasenra (benralizumab) — brief drug definition

Drug classFasenra (benralizumab) is a monoclonal antibody to the IL-5 receptor alpha leading to depletion of eosinophils and basophils

Dosing formatAdministered subcutaneously; trial regimens include 30 mg dosing with maintenance intervals (q8w) after initial dosing

Clinical evidenceDemonstrated reduction in exacerbation rates in CALIMA and SIROCCO trials (primary analyses focused on baseline eosinophils >=300 cells/µL)

inv-59: Cinqair (reslizumab) — brief drug definition

Drug classCinqair (reslizumab) is a humanized monoclonal antibody that binds IL-5, interrupting IL-5 signaling to reduce eosinophilia

AdministrationGiven IV at weight-based dosing (policy dose limit 3 mg/kg every 4 weeks)

Efficacy and safety notePivotal trials (studies 3082/3083) showed reduced exacerbation rates and improved FEV1; safety signals include rare anaphylaxis and CPK elevations

inv-60: eosinophilic granulomatosis with polyangiitis — abbreviation/definition (EGPA)

AbbreviationEGPA = eosinophilic granulomatosis with polyangiitis

Policy contextEGPA is included as a labeled indication in Nucala and (per updates) Fasenra criteria with specific eosinophil and clinical requirements

ThresholdsPolicy references EGPA criteria using percent or absolute eosinophil thresholds (e.g., >=10% or absolute >=1000 cells/mcL)

inv-61: chronic rhinosinusitis with nasal polyps — abbreviation/definition (CRSwNP)

AbbreviationCRSwNP = chronic rhinosinusitis with nasal polyps

Policy inclusionNucala (mepolizumab) has labeled CRSwNP indication with specific symptom and prior therapy requirements in the policy

Prior therapy requirementsPolicy requires failed intranasal corticosteroids and prior systemic steroids or prior bilateral nasal polyp surgery depending on update timing

inv-62: CRSwNP — policy-history abbreviation note

Historical abbreviation noteCRSwNP is used as an abbreviation in policy history entries documenting Nucala updates for nasal polyps

ContextPolicy history entries (2021 onward) reference CRSwNP when recording coverage and criteria changes for nasal polyps indications

Related updatesHistory records multiple interim updates to CRSwNP criteria including surgery and prior steroid requirements

Asthma criteria eosinophil threshold for Nucala, Fasenra, and Cinqair changed from ≥150 cells/µL to ≥300 cells/µL (effective following 90-day provider notification).

2025-02-01eosinophil_threshold_reversion_and_sos_exception

Eosinophil threshold for Nucala, Fasenra, and Cinqair reverted from ≥300 cells/µL back to ≥150 cells/µL; Site-of-Service medical necessity criteria clarified to not apply to Alaska fully-insured members per Alaska HB 226 and non-formulary exceptions may be authorized up to 12 months.

2025-04-01diagnostic_criteria_change

Removed requirement to confirm asthma with an eosinophilic phenotype documented in the previous 12 months and changed 'maximum doses' to 'maximum tolerated doses' of inhaled corticosteroid in asthma coverage criteria.

2025-07-01fev1_and_sos_addition

Asthma criteria updated to add FEV1/FVC <0.80 with asthma worsening on steroid taper as an option; site-of-service review was added for Fasenra and Nucala (effective Oct 3, 2025 after provider notification).

2025-08-01sos_injection_application_and_copd

Clarified that Site-of-Service medical necessity criteria can apply to injection drugs and Nucala coverage extended to certain COPD patients.

2025-10-01crsnp_surgery_requirement_change

Nucala CRSwNP criteria revised to remove requirement for at least one nasal polyp surgery within the last 10 years and instead require prior systemic corticosteroids in last 2 years or prior bilateral nasal polyp surgery.

2025-11-01egpa_clarification_and_copd_change

EGPA criteria updated to clarify presence of ANCA meets requirement; COPD criteria for Nucala further refined (removal of chronic bronchitis sign/symptom requirement).

2026-02-01eosinophil_and_testing_exceptionsLatest

Asthma criteria updated to allow blood eosinophil count ≥150 cells/µL, permit use of oral/systemic corticosteroids for exacerbations, and allow exceptions for individuals unable to discontinue corticosteroids for eosinophil testing; EGPA absolute eosinophil threshold lowered from ≥1500 to ≥1000 cells/µL.