ModifiedPremera BluecrossPolicy N/A

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

Defines medical necessity, site-of-service review, and coverage criteria for IL-5 inhibitor drugs (reslizumab, benralizumab, mepolizumab) for various eosinophilic conditions and related administration requirements affecting providers who prescribe or administer these agents.

Policy Summary

PayerPremera Bluecross

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

Policy CodePolicy N/A

Change TypeCriteria and site-of-service updates

Effective DateOct 3, 2025

Next Review DateSep 9, 2025

Key ActionDocument age, baseline eosinophil counts, prior exacerbations or lung function, and adherence to maximum tolerated inhaled corticosteroid/LABA therapy when requesting authorization.

SourceLink

POLICY UPDATE CHANGES

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

Asthma eosinophil count criteria for Nucala, Fasenra, and Cinqair were changed multiple times between 150 and 300 cells/mcL in the last 12 months during 2024–2025 updates.

Clarified that the listed medications are subject to the product's FDA dosage and administration prescribing information.

Added site-of-service review requirements for Fasenra and Nucala and clarified Site of Service Medical Necessity exceptions for Alaska fully-insured members per Alaska HB 226.

Updated asthma diagnostic and exacerbation criteria to require two or more exacerbations in prior 12 months or other specified events or FEV1/FVC criteria.

Prohibition on combination biologic therapy: policy requires that these biologics not be used in combination with each other (e.g., Dupixent, Xolair, Tezspire).

Added quantity limits consistent with prescribing information for Cinqair, Nucala, and Fasenra.

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.

IL-5 inhibitor drugs addressed

12 monthsmax approval duration

>=13age for SOS review

Age ≥ 6Fasenra/Nucala min age

150↔300eosinophil threshold toggle

Coverage Criteria for IL-5 Inhibitors

inv-01: Cinqair (reslizumab) — severe eosinophilic asthma

Covered when ALL of the following are met:

Cinqair asthma criteria: Individual aged 18 years or older; using maximum tolerated inhaled corticosteroid; using an inhaled long-acting beta-agonist (LABA); and meets one of: ≥2 asthma exacerbations in prior 12 months requiring oral corticosteroids, OR ≥1 exacerbation requiring hospitalization/ED/urgent care in prior 12 months, OR FEV1 <80% predicted, OR FEV1/FVC <0.80, OR asthma worsens when tapering oral corticosteroids.

Supported by policy site-of-service and Cinqair-specific criteria (chunk 7).

inv-02: Fasenra (benralizumab) — severe eosinophilic asthma and EGPA

Covered when ALL of the following are met:

Fasenra asthma criteria: Individual aged ≥6 years; using maximum tolerated inhaled corticosteroid; using an inhaled long-acting beta-agonist (LABA); and meets one of: ≥2 exacerbations in prior 12 months requiring oral corticosteroids, OR ≥1 exacerbation requiring hospitalization/ED/urgent care in prior 12 months, OR FEV1 <80% predicted, OR FEV1/FVC <0.80, OR asthma worsens when tapering oral corticosteroids. Additionally must have at least one: blood eosinophils >150 cells/mcL, sputum eosinophils ≥3%, or oral corticosteroid–dependent asthma not able to discontinue for testing.

Age, background therapy, exacerbation/FEV1 criteria and eosinophil requirements per chunks 9-10.

Fasenra EGPA criteria: Individual aged ≥18 years; history or presence of asthma; stable prednisone/prednisolone 7.5–50 mg with or without additional immunosuppressive therapy; blood eosinophil level ≥10% OR absolute eosinophil count threshold as specified; and polyangiitis documented by biopsy or listed clinical findings (eg alveolar hemorrhage, palpable purpura, myocardial infarction due to coronary arteritis, hematuria with red cell casts, leukocytoclastic vasculitis, mononeuritis, or other systemic manifestations).

EGPA-specific requirements and prescriber specialty noted in chunk 10.

inv-03: Nucala (mepolizumab) — asthma, COPD, EGPA, HES, CRSwNP

Covered when ALL of the following are met (indication-specific):

Nucala asthma criteria: Individual aged ≥6 years; using maximum tolerated inhaled corticosteroid; using an inhaled long-acting beta-agonist (LABA); and meets one of: ≥2 exacerbations in prior 12 months requiring oral corticosteroids, OR ≥1 exacerbation requiring hospitalization/ED/urgent care in prior 12 months, OR FEV1 <80% predicted, OR FEV1/FVC <0.80, OR asthma worsens when tapering oral corticosteroids. Also requires at least one: blood eosinophils >150 cells/mcL, sputum eosinophils ≥3%, or oral corticosteroid–dependent asthma not able to discontinue for testing.

Asthma age, controller therapy, exacerbation and eosinophil criteria per chunks 11-12.

Nucala COPD criteria: Individual aged ≥18 years with inadequately controlled COPD; blood eosinophils ≥150 cells/mcL within the prior 12 months; prior trial of LAMA/LABA combination for ≥90 days (unless not tolerated) with persistent symptoms; and meets exacerbation criteria: ≥2 exacerbations treated with systemic corticosteroid and/or antibiotic in prior 12 months OR ≥1 exacerbation requiring hospitalization; plus signs or symptoms of chronic bronchitis for ≥3 months in prior 12 months.>=150 cells/mcL within last 12 months

COPD-specific criteria and prior therapy requirements per chunk 13.

inv-04: Concomitant medication exclusions

No combination biologic therapy: IL-5 inhibitors (Cinqair, Fasenra, Nucala) will not be used in combination with Dupixent (dupilumab), Tezspire (tezepelumab-ekko), Xolair (omalizumab), or each other for asthma or CRSwNP when these medications are being used to treat those conditions.

Combination therapy prohibition and exclusions described in chunk 16.

inv-05: Site of service medical necessity

When hospital-based outpatient setting is medically necessary: Initial course of infusion/injection or re-initiation after ≥6 months AND no outpatient infusion center within 50 miles and no contracted home infusion agency available, OR individual has a clinical condition that increases risk for infusion/injection (eg symptomatic cardiac arrhythmia, significant respiratory disease with %FVC ≤40%, unstable renal function, difficult vascular access, cognitive impairment impacting safety, or prior severe adverse drug reaction/anaphylaxis).

Site-of-service medical necessity criteria and examples per chunks 6-7.

inv-06: Continuation / Site-of-Service Renewal

Non-formulary exception reviews and other reviews for IL-5 agents may be approved up to 12 months if medical necessity criteria are met and ongoing response is documented as follows:

Continuation authorization conditions

Asthma general response measures: Decrease in requirement for oral steroids OR decrease in exacerbation frequency OR decrease in ER/urgent care visits OR decrease in hospitalizations OR decrease in frequency and severity of symptoms OR increase in quality-of-life and ability to perform activities of daily livingclinical improvement documented
Apply for asthma indications (chunk 18).
HES response measure (Nucala): Decrease in number or severity of Hypereosinophilic Syndrome (HES) flares from baselineclinical improvement documented
Applies to mepolizumab for HES (chunk 18).

inv-07: Efficacy linked to eosinophil thresholds

Covered when evidence shows clinically meaningful benefit in specified eosinophil-defined populations and per product labeling:

Baseline eosinophil and evidence: Therapy demonstrates greater reductions in exacerbation rates and improvements in FEV1 in populations with baseline blood eosinophil counts >=150 cells/µL and often >=300 cells/µL; many pivotal analyses report statistically significant benefit in these subgroups.baseline eosinophils >=150 or >=300 cells/µL

Multiple trial subgroup analyses (SIROCCO, CALIMA, pooled analyses) show stronger effects at higher eosinophil thresholds (chunks 36, 38, 40, 42).

inv-08: Safety considerations

Consider contraindications and safety signals when determining coverage:

Serious adverse events and monitoring: Safety signals include deaths in trials (not necessarily treatment-related), serious adverse events such as worsening asthma, anaphylaxis (reslizumab), and creatine phosphokinase elevations; immunogenicity observed with benralizumab but not associated with reduced efficacy. Monitor per product labeling.monitor per product labeling

Reslizumab anaphylaxis and CPK signals and benralizumab immunogenicity reported in chunks 48 and 43.

inv-09: Initial therapy / general coverage criteria

Covered when ALL of the following are met (summary of updated/recorded elements):

Age and product dosing: Product-specific age requirements must be met (for example, Fasenra age ≥6 years; Cinqair and some Nucala indications have older minimum ages) and FDA dosing/administration prescribing information must be followed.

Age and dosing updates recorded in policy history and 2024–2025 updates (chunks 56, 71, 72).

Eosinophil criterion: A qualifying blood eosinophil count is required; policy thresholds toggled between 150 and 300 cells/mcL in 2024–2025 updates and were restored to 150 cells/mcL within the last 12 months per 02/01/25 history; verify indication-specific thresholds in the full policy.>=150 cells/mcL within the last 12 months

Documented threshold and history of changes (chunks 56, 58, 71).

Exacerbation or lung function criteria: Individual has ≥2 asthma exacerbations in prior 12 months requiring oral corticosteroids, OR ≥1 exacerbation requiring hospitalization/ED/urgent care in prior 12 months, OR FEV1 <80% predicted, OR FEV1/FVC <0.80, OR asthma worsens on OCS taper; must meet one of these to qualify.

All uses of Cinqair (reslizumab), Fasenra (benralizumab), and Nucala (mepolizumab) that are not specifically described in this policy are considered investigational. This includes use for other eosinophilic conditions or for acute bronchospasm/status asthmaticus and any indication not covered by the listed product-specific medical necessity statements.

Site-of-service review under this policy is limited to individuals aged 13 years or older. Pediatric site‑of‑service provisions do not apply to children under age 13 because pediatric administration often requires specialty infusion training, size‑appropriate equipment, and other age‑specific considerations.

Pivotal trial subgroup analyses for reslizumab identified populations with little or no demonstrated benefit, including adolescents and certain racial groups and US‑only subjects. The absence of meaningful effect in these subgroups was noted in the trial reviews and may justify more restrictive coverage decisions or denial when the requesting patient matches these less‑responsive populations.

The policy prohibits concurrent use of the IL‑5 inhibitors with each other or with other biologics for asthma or CRSwNP (for example, Dupixent [dupilumab], Xolair [omalizumab], Tezspire [tezepelumab‑ekko]). Requests for combination biologic therapy are excluded and would not meet medical necessity under this policy.

Hospital‑based outpatient settings and other facility locations are considered not medically necessary for infusion or injectable therapy when the site‑of‑service criteria in this policy are not met. Examples include situations where the defined clinical risks, distance, or other site‑specific justifications are absent.

Failure to submit required documentation (office visit notes with diagnosis, relevant history, laboratory values, physical exam, and medication history) or inability to demonstrate a documented clinical response per the policy’s response parameters (for example decreased oral steroid need, fewer exacerbations, fewer ED visits/hospitalizations, or indication‑specific improvements) may result in denial of initial requests or non‑renewal.

Evidence for combined use of IL‑5 inhibitors with dupilumab (dupilumab) or omalizumab (omalizumab) is limited to a few case reports and is not robust. Therefore combination therapy with these agents is not supported by the available evidence and is generally not considered medically necessary without strong, documented justification.

Site‑of‑Service Medical Necessity criteria do not apply to Alaska fully‑insured members per Alaska HB 226; for those members only the infusion medical necessity criteria apply. This exception was recorded in the policy history and clarifications effective in early 2025.

Codes, Thresholds, and Key Numeric Criteria

Reviewed for Medical Necessity HCPCS CodesHCPCS

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

Coding history entriesHCPCS

J2182	HCPCS code added effective 1/1/17 (as recorded in history)
J0517	HCPCS code added effective 1/1/19 (as recorded in history)
J2786	Cinqair (reslizumab) HCPCS code referenced (coverage effective Aug 7, 2020)

inv-20: Blood eosinophil count — >150 cells/mcL (or sputum eosinophils ≥3% for some criteria)

Policy threshold (as stated)Blood eosinophil count greater than 150 cells/mcL (sputum eosinophils ≥3% accepted for some criteria)

Context — asthma criteriaRequired as one of at least one qualifying findings for severe eosinophilic asthma (eg, with ≥2 exacerbations or FEV1/FVC or FEV1 criteria)

Test specimenPeripheral blood eosinophil count; sputum eosinophil ≥3% accepted where specified

inv-21: HES eosinophil threshold — ≥ 1,000 cells/microL

Policy threshold (HES)Blood eosinophil level ≥1,000 cells/microL

Indication

Prior Authorization, Documentation, and Provider Requirements

Documentation Required

Clinical and laboratory documentation required

Providers must submit clinical and laboratory documentation to support medical necessity for all reviews. Documentation should include office visit notes with diagnosis, relevant medical history, physical exam, medication history (including inhaled corticosteroid and LABA regimens and doses), and recent laboratory values such as blood eosinophil counts. For asthma and related indications, include prior exacerbation history, prior treatment trials, baseline and follow-up measures (e.g., FEV1, FEV1/FVC), and objective response measures (decrease in oral steroid use, reduction in exacerbations/ED visits/hospitalizations, symptom improvement, or quality-of-life gains). Lack of documentation of ongoing positive clinical response on re-authorization may result in denial.

Office visit notes with diagnosis, history, exam, medication history
Baseline and recent blood eosinophil count (timing per indication)
Prior exacerbations, hospitalizations, ED/urgent care visits in prior 12 months
Baseline and follow-up pulmonary function (FEV1, FEV1/FVC) where applicable
Documentation of prior biologic or steroid-sparing response when relevant
Chart notes documenting positive clinical response for continuations (e.g., decreased oral steroid requirement, fewer exacerbations, improved symptoms/quality of life)

Background and Rationale

Eosinophils are circulating white blood cells that promote inflammation and contribute to airway inflammation in eosinophilic asthma and other disorders. Interleukin‑5 (IL‑5) is a key cytokine driving eosinophil development, activation, and survival. IL‑5 pathway inhibitors (mepolizumab, reslizumab) bind IL‑5 and reduce eosinophil counts, while benralizumab targets the IL‑5 receptor alpha subunit to deplete eosinophils. Reducing eosinophilia with IL‑5 pathway blockade is the therapeutic mechanism underlying the clinical benefits observed in trials for severe eosinophilic asthma and select eosinophilic conditions.

Definitions and Key Terms

inv-46: Eosinophil count — definition and unit expectations

DefinitionEosinophil count = laboratory measurement of the number (or percentage) of eosinophils, a white blood cell type implicated in eosinophilic diseases

Specimen/unit expectationReported as cells/mcL (cells per microliter) or as a percentage in sputum when specified (eg sputum eosinophils ≥3%)

Clinical interpretationElevated blood or sputum eosinophils support eosinophilic phenotype and may indicate reduced responsiveness to inhaled corticosteroids alone

inv-47: IL-5 inhibitors — agents and mechanism (mepolizumab, benralizumab, reslizumab)

Agents in classMepolizumab (Nucala), benralizumab (Fasenra), reslizumab (Cinqair)

Mechanism summaryMonoclonal antibodies targeting IL-5 or the IL-5 receptor to reduce eosinophil-mediated inflammation (mepolizumab and reslizumab bind IL-5; benralizumab binds IL-5 receptor alpha)

Policy Revision History

2016-01-12policy_created

New policy created and added to Medical subsection; considered medically necessary for labeled indications when criteria are met.

2017-01-01coding_update

HCPCS code J2182 added to coding table effective 01/01/2017.

2019-01-01coding_update

HCPCS code J0517 added effective 01/01/2019.

Policy Summary

PayerPremera Bluecross

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

Policy CodePolicy N/A

Change TypeCriteria and site-of-service updates

Effective DateOct 3, 2025

Next Review DateSep 9, 2025

Key ActionDocument age, baseline eosinophil counts, prior exacerbations or lung function, and adherence to maximum tolerated inhaled corticosteroid/LABA therapy when requesting authorization.

SourceLink

On This Page

Nucala EGPA criteria: Individual aged ≥18 years; history or presence of asthma; stable prednisone/prednisolone 7.5–50 mg with or without additional immunosuppressive therapy; blood eosinophil level ≥10% OR absolute eosinophil count ≥1500 cells/microL; and polyangiitis documented by biopsy or listed clinical findings.

EGPA criteria and dosing/prescriber details per chunks 11 and 14.

Nucala HES criteria: Individual aged ≥12 years; documented hypereosinophilic syndrome (HES) for ≥6 months without identifiable non-hematologic secondary cause; FIP1L1–PDGFRA negative; blood eosinophils ≥1,000 cells/microL; ≥2 HES flares requiring escalation in past 12 months; receiving background HES therapy ≥4 weeks prior to initiation; and prescribed by or in consultation with a hematologist.>=1000 cells/microL

HES-specific eligibility and prescriber requirement per chunk 15.

Nucala CRSwNP criteria: Individual aged ≥18 years with inadequately controlled bilateral chronic rhinosinusitis with nasal polyps (CRSwNP); at least 2 symptoms (facial pressure, moderate–severe nasal congestion/obstruction, or significant loss of smell); prior failure of intranasal corticosteroid monotherapy; prescribed with intranasal corticosteroid; and either prior systemic corticosteroid use for nasal polyps in last 2 years or prior bilateral nasal polyp surgery. Dose prescribed 100 mg subcutaneously every 4 weeks.

CRSwNP criteria and dosing per chunk 16.

CRSwNP response measures (Nucala): Decrease from baseline of nasal polyp size AND improvement in nasal congestion score (NCS) or documented decrease from baseline of nasal congestionboth required

NCS scale provided in policy (chunk 18).

Diagnostic/exacerbation criteria updated effective Jan 3, 2025 and further clarified in history (chunks 56, 58, 71, 72).

Background therapy and prior use: Must have been on appropriate background inhaled corticosteroid and bronchodilator therapy at maximum tolerated doses prior to biologic therapy.

Policy language changed from 'maximum dose' to 'maximum tolerated dose' (chunks 58, 72); see appendix for specific inhaled corticosteroid regimens.

Combination therapy exclusion: The biologic must not be used concurrently with other listed biologics for asthma or CRSwNP (eg Dupixent, Xolair, Tezspire, or other IL-5 inhibitors).

Combination therapy prohibition added in 2024 and reiterated in updates (chunks 56, 16).

Hypereosinophilic syndrome (HES) — Nucala specific requirement

Additional requirementDocumented HES ≥6 months and exclusion of FIP1L1–PDGFRA positive disease

inv-22: EGPA eosinophil thresholds — ≥ 10% or absolute eosinophil count ≥ 1500 cells/microL

Policy thresholds (EGPA)Blood eosinophil level ≥10% OR absolute eosinophil count ≥1,500 cells/microL

Indication contextEGPA (eosinophilic granulomatosis with polyangiitis) — Nucala EGPA criteria require these eosinophil thresholds plus clinical/lab documentation

Prescriber requirementMedication prescribed by or in consultation with an allergist/immunologist or pulmonologist (EGPA criteria note prescriber specialties)

inv-23: Blood eosinophil count — trial-subgroup examples (>=300 cells/mcL and other thresholds)

Common trial subgroup example>=300 cells/mcL (primary analysis group in several pivotal trials such as DREAM and MENSA)

Alternate subgroup used>=150 cells/mcL (used in some analyses and entry criteria)

Historical/reference useTrials report benefit gradients across thresholds (eg 150–299, ≥300) when analyzing efficacy

inv-24: Baseline blood eosinophil count thresholds — commonly analyzed ranges (<150, >=150, >=300, etc.)

Analyzed baseline rangesCommonly analyzed categories: <150, ≥150, ≥300 cells/µL (and subgroups 150–299, 300–449, ≥450)

Evidence notePivotal trials (eg SIROCCO, CALIMA, benralizumab analyses) show larger treatment effects at higher baseline eosinophil strata

Use in decisionsBaseline category selected influences expected exacerbation-rate reduction and FEV1 change interpretations

inv-25: blood eosinophil count — policy-stated 150 cells/mcL within the last 12 months (policy toggled 150↔300 in updates)

Policy operational threshold (current recorded)Blood eosinophil count ≥150 cells/mcL within the last 12 months (policy toggled between 150 and 300 in 2024–2025 updates)

Change historyAsthma eosinophil criterion was changed to 300 cells/mcL effective Jan 3, 2025, then reverted to 150 cells/mcL in 2025 history entries

VerificationConfirm product-specific criteria in the full policy for indication-specific requirements and time window

inv-26: FEV1/FVC — <0.80 added as an option for qualifying asthma with worsening on OCS taper

Added lung function optionFEV1/FVC <0.80 may be used as an option to qualify asthma with worsening on oral corticosteroid taper

Context of useIncluded among qualifying criteria where an individual meets one of: exacerbations, FEV1 <80% predicted, FEV1/FVC <0.80, or worsening on OCS taper

Effective changeFEV1/FVC <0.80 added in 2025 history updates to asthma coverage criteria

Denial Risk

Site-of-service denial triggers

Site-of-service review applies for listed drugs. Requests for administration in a non-preferred site (e.g., hospital outpatient instead of home or outpatient infusion center) will be denied when site-of-service medical necessity criteria are not met. Site-of-service medical necessity is limited to situations such as no outpatient infusion center within 50 miles, no contracted home infusion agency available, or when the individual has clinical risk factors that increase complication risk (for example unstable cardiac or pulmonary disease, unstable vascular access, acute cognitive impairment, unstable renal function, history of severe anaphylaxis).

Denial risk when outpatient infusion center within 50 miles or home infusion available and site-of-service criteria not met
Clinical risk factors that may justify non-standard site: symptomatic cardiac arrhythmia, significant respiratory disease (eg, FVC ≤ 40%), unstable renal function, difficult vascular access, acute cognitive/mental status changes, prior severe anaphylaxis
Site-of-service exception for cytokine release syndrome (CRS) when criteria met

Denial Risk

Age-based site-of-service limitation

Site-of-service review is limited by age. Pediatric physiologic and developmental differences necessitate specialized infusion resources; therefore site-of-service review and restrictions in this policy apply only to individuals aged 13 years and older. Requests for site-of-service exceptions for younger pediatric patients should account for pediatric-specific needs and may be denied under this policy.

Site-of-service review limited to individuals ≥ 13 years of age
Pediatric-specific infusion considerations (equipment, dosing, behavioral management) are the rationale for the age limitation

Note

Trial data to support requests

When relevant to a request, include pivotal trial safety and efficacy data or summaries (for example, key trial endpoints, population, and major safety signals) to support clinical rationale for use outside standard labeling or for complex cases. Trial data are especially relevant for requests involving combination therapy, off-label indications, or where subgroup analyses affect expected benefit.

Provide pivotal trial efficacy endpoints (e.g., exacerbation rate reductions, FEV1 changes) when supporting medical necessity
Provide safety summaries from pivotal trials if safety concerns or subgroup findings (e.g., age, region, comorbidities) affect expected benefit
Case reports or limited evidence for combination biologic therapy should be accompanied by trial or literature justification

Prior Authorization

Background controller therapy requirement

For asthma indications, individuals must be on appropriate background controller therapy prior to initiation of IL-5 pathway biologics. The policy requires use of a long-acting beta-agonist (LABA) in combination with an inhaled corticosteroid (ICS) at maximum tolerated dose. Document attempts at optimization of non-biologic therapy and adherence.

Requirement: inhaled LABA plus inhaled corticosteroid at maximum tolerated dose prior to IL-5 biologic initiation
Document adherence and optimization of inhaled controller therapy
If maintenance oral corticosteroids are in use, document exacerbation history and attempts to taper

Documentation Required

Background controller therapy documentation

Support documentation must enumerate the inhaled corticosteroid regimen and dose ranges to demonstrate high/maximum tolerated dosing per policy high-dose definitions. Use the listed high-dose ICS regimens when documenting prior controller therapy.

Include specific ICS product and daily dose (examples in policy high-dose regimens: beclomethasone, budesonide, ciclesonide, fluticasone propionate/furoate, mometasone) to show high or maximum tolerated dosing
If patient cannot tolerate high doses, document adverse effects or reasons for dose limitation
Document concurrent LABA use and dosing

Therapeutic roleUsed as add-on maintenance therapy for severe eosinophilic asthma and other eosinophilic disorders per product labeling

inv-48: Nasal Polyp Score (NPS) — endoscopic bilateral nasal polyp score 0-8 used in CRSwNP trials

Scoring rangeEndoscopic bilateral Nasal Polyp Score (NPS) ranges from 0 to 8 (each side graded 0–4)

Use caseNPS employed in CRSwNP trials (eg SYNAPSE) to assess polyp burden and treatment effect

Thresholds used in trialsSYNAPSE required baseline bilateral NPS ≥5 with ≥2 in each nasal cavity for enrollment

inv-49: Reslizumab (Cinqair) — brief agent definition

Agent definitionReslizumab (Cinqair) is a humanized monoclonal antibody that binds IL‑5, preventing IL‑5 from binding its receptor and thereby reducing eosinophilia and airway inflammation

Therapeutic implicationIndicated as add‑on therapy for severe eosinophilic asthma in adults (policy notes prescribing/consult requirements)

Safety signalsPooled trials identified safety concerns including anaphylaxis and muscle toxicity (see safety section)

inv-50: maximum tolerated inhaled corticosteroid — definition replacing 'maximum dose' language

Definition (policy language)Maximum tolerated inhaled corticosteroid = the inhaled corticosteroid dose tolerated by the individual (policy language replaced 'maximum dose' with 'maximum tolerated dose')

RationaleChange accounts for individual tolerability when assessing whether background controller therapy was optimized prior to biologic initiation

Reference/appendixSee Appendix for examples of inhaled corticosteroid and combination agents used when assessing background therapy

2020-08-07coverage_addition

Coverage criteria for Cinqair (reslizumab) added; HCPCS code J2786 referenced and coverage effective for dates of service on or after 08/07/2020.

2024-06-01material_update

Fasenra (benralizumab) minimum age requirement updated from 12 years to 6 years (recorded May–June 2024) and combination-therapy prohibition and quantity limits added per prescribing information.

2024-10-01effective_change_notification

Policy changes scheduled effective 2025-01-03 after provider notification: asthma eosinophil criterion changed from 150 to 300 cells/mcL and diagnostic and prescriber requirements updated.

2025-02-01annual_review_material_update

Annual review approved 01/14/2025 reinstated asthma eosinophil criterion to 150 cells/mcL, clarified Site of Service Medical Necessity exception for Alaska fully-insured members, and confirmed non-formulary exception authorizations may be approved up to 12 months.

2025-07-01interim_update

Interim review approved 06/10/2025 changed wording to 'maximum tolerated' inhaled corticosteroid and added FEV1/FVC <0.80 and worsening on OCS taper as qualifying asthma options (approved 07/01/2025 entry recorded).

2025-10-03site_of_service_additionLatest

Site-of-service review added for Fasenra and Nucala effective 10/03/2025 (provider notification dated prior to effective date).

2024-06-01age_requirement_change

Fasenra (benralizumab) minimum age requirement updated from 12 years to 6 years as part of the 2024 updates.

2024-06-01combination_therapy_prohibition

Policy updated to prohibit combination use of listed biologics (including Xolair, Dupixent, Tezspire and the IL-5 inhibitors) for treatment of asthma and to add quantity limits per prescribing information.

2025-01-03eosinophil_threshold_change

Asthma baseline blood eosinophil criterion for Nucala, Fasenra, and Cinqair was changed from 150 cells/mcL to 300 cells/mcL effective January 3, 2025 (per 2024 notice), then restored to 150 cells/mcL in the 02/01/2025 annual review.

2025-02-01site_of_service_exception_clarification

Clarified that Site of Service Medical Necessity criteria do not apply to Alaska fully-insured members (Alaska HB 226) and confirmed adherence to FDA dosing/administration; non-formulary exception authorizations may be approved up to 12 months.

2025-07-01diagnostic_criteria_updateLatest

Asthma diagnostic criteria updated to require two or more exacerbations in prior 12 months or specified events and added FEV1/FVC <0.80 and worsening on OCS taper as qualifying options (recorded in 07/01/25 history entries; effective dates noted in history).