ModifiedCignaPolicy IP0422

Immunologicals - Nucala

Defines Cigna prior authorization, medical necessity criteria, dosing, durations, and not-covered uses for mepolizumab (Nucala) for FDA-approved indications (asthma, COPD, CRSwNP, EGPA, HES) and exclusions. Applies to prescription benefit coverage and requires specialist prescribing/consultation.

Policy Summary

PayerCigna

PolicyImmunologicals - Nucala

Policy CodePolicy IP0422

Change TypeRevisions to indications, eosinophil timing, and approval durations (MODIFIED)

Effective Date

Next Review Date

Key ActionPrior Authorization is recommended for prescription benefit coverage of Nucala; approvals provided for specified durations (months defined as 30 days).

POLICY UPDATE CHANGES

Updated coverage policy title from 'Mepolizumab' to 'Immunologicals - Nucala'.

Asthma: updated diagnostic criteria requirements for confirmation of asthma and clarified eosinophil level timing; initial approval duration changed from 12 months to 6 months.

COPD: new indication and criteria added including age ≥18, eosinophil requirement ≥300 cells/µL, trial of inhaled therapies, exacerbation history, and specialist involvement.

EGPA: clarified systemic corticosteroid requirement to 'currently receiving' for a minimum of 4 weeks and eosinophil timing clarified to within previous 4 weeks OR prior to monoclonal antibody therapy; initial approval duration changed to 9 months.

HES: initial approval duration changed from 12 months to 8 months and eosinophil timing clarified to prior to any monoclonal antibody therapy that may alter blood eosinophil levels.

Throughout policy: added Ebglyss and Nemluvio to examples of monoclonal antibody therapies in selected revision; later removed in another revision.

Eosinophil level requirement timing clarified to require level ≥ 150 cells/microliter within the previous 4 weeks OR taken prior to treatment with a monoclonal antibody that may alter blood eosinophil levels (previously 6 weeks).

Eosinophil level requirements for Hypereosinophilic Syndrome clarified to require level be taken prior to treatment with any monoclonal antibody therapy that may alter blood eosinophil levels.

Revision history entries indicate Selected Revision dates and Annual Revision notes (e.g., Selected Revision 2 = 12/15/2024; Annual Revision 2 = 7/15/2025).

Ebglyss and Nemluvio were previously removed from examples of monoclonal antibody therapies in an earlier revision note.

5FDA-Approved Indications Covered

6Initial Approval Durations (months) listed

1HCPCS code listed

1Policy Number

>=150Eosinophil threshold

4Recent eosinophil test window (weeks)

Coverage Summary

Coverage stance: covered with criteria for Nucala (mepolizumab) for the FDA‑approved indications of asthma, COPD, chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic granulomatosis with polyangiitis (EGPA), and hypereosinophilic syndrome (HES). The policy applies to the prescription benefit and requires prior authorization, specialist prescribing/consultation, documentation of required prior therapies, and adherence to dosing and duration criteria. Coverage and medical necessity align with FDA labeling, pivotal trial enrollment criteria, and guideline-based evidence as summarized in the policy.

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Initial Therapy Criteria (by indication)

Covered when ALL of the following are met:

ALL of the following

Documentation of the specific indication: Asthma, COPD, CRSwNP, EGPA, or HES (see respective indication-specific criteria below).
Eosinophil Level Requirement (one of):
- Peripheral blood eosinophil count ≥ 150 cells/µL within 4 weeks prior to request or prior to initiation of monoclonal antibody therapy.
- Peripheral blood eosinophil count ≥ 300 cells/µL at any time in the past 12 months.
- For HES only: baseline blood eosinophil count ≥ 1,000 cells/µL prior to monoclonal antibody therapy (see HES criteria).
Indication-specific criteria (select the branch matching the diagnosis):
- Asthma — Initial Therapy
  - Age ≥ 6 years (per FDA indication).
    Policy applies to patients meeting plan age limits.
  - Diagnosis of severe asthma with an eosinophilic phenotype.
  - Lung function criteria (choose one):
    Option a: Demonstration of airflow limitation with FEV1 < 80% predicted after bronchodilator withholding and objective evidence of reversibility or variability consistent with asthma.
    Use when available; see pulmonary function test documentation.
    Poor symptom control: Asthma Control Questionnaire consistently ≥ 1.5 or Asthma Control Test < 20.

Continuation Therapy Criteria (by indication)

Typical continuation approvals are provided for 1 year when continuation criteria are met (e.g., patient has completed the required initial treatment period and demonstrates clinical benefit). For initial and continuation authorization calculations, the policy defines 1 month as equal to 30 days.

Dosing by Indication

Eosinophil Level Requirements & Timing

Not Medically Necessary / Exclusions

Not Medically Necessary Uses

Uses considered not medically necessary (deny) if the request is for ANY of the following:

Not medically necessary uses: Atopic dermatitis; Concurrent use of Nucala with another monoclonal antibody therapy; Eosinophilic esophagitis, eosinophilic gastroenteritis, or eosinophilic colitis (eosinophilic GI disorders)

This list may not be all-inclusive

Applicable Codes

Considered Medically Necessary when criteria metHCPCSCovered

J2182

Injection, mepolizumab, 1 mg

Policy Identifiermixed

IP0422

Coverage Policy Number

Provider Actions & Authorization Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for medical benefit coverage of Nucala (mepolizumab). Prior authorization is also recommended/required for prescription benefit coverage. Approvals are duration-limited; when approved, authorization durations are based on 30-day months.

Affected codes: J2182
Common approval durations: 1 month (30 days), 3 months (90 days), 6 months (180 days), 12 months (360 days) — durations expressed as 30-day months

Documentation Required

Specialist Prescribing / Consultation Requirement

Prescribing or consultation by an appropriate specialist is required or recommended depending on the indication. Document involvement of a specialist as part of the prior authorization request.

Clinical Evidence

>=150Asthma trial enrollment threshold (≥150 cells/µL at screening or ≥300 cells/µL during prior year); efficacy seen as early as 24 weeks

>=300COPD MATINEE enrollment threshold (≥300 cells/µL at screening; ≥150 cells/µL within prior 12 months) with background triple therapy ≥3 months

>=1000HES pivotal trial baseline requirement (≥1,000 cells/µL); efficacy assessed at 32 weeks

Evidence summary: pivotal randomized trials for asthma, COPD, EGPA, and HES required elevated peripheral blood eosinophil counts for enrollment (for example, asthma trials used screening thresholds of ≥150 cells/µL at screening or ≥300 cells/µL during the prior year; MATINEE for COPD required ≥300 cells/µL at screening and ≥150 cells/µL within 12 months; the HES trial required baseline eosinophils of ≥1,000 cells/µL). Efficacy in some indications was assessed as early as 24 weeks (asthma) and 32 weeks (HES).

Clinical guidelines support biologic therapy in selected patients with eosinophilic phenotypes: GINA and ERS/ATS recommend anti‑IL‑5 therapy (including mepolizumab) as add‑on treatment for severe eosinophilic asthma; GOLD recognizes triple inhaled therapy for COPD with elevated eosinophils though Nucala is not yet in GOLD recommendations; JTFPP and other ENT guidelines support biologics for CRSwNP in patients with inadequate response to intranasal corticosteroids; rheumatology guidance (ACR/EULAR) supports Nucala for non‑severe or relapsing EGPA; WHO/international HES guidance lists Nucala as a second‑line option. These guideline positions and trial enrollment thresholds inform the policy criteria for patient selection and expected clinical benefit.

Background & Definitions

Background and mechanism: Nucala (mepolizumab) is an interleukin‑5 (IL‑5) antagonist monoclonal antibody indicated as add‑on maintenance therapy for eosinophilic phenotypes of asthma, COPD, CRSwNP, EGPA, and HES. The policy notes that Nucala is not for relief of acute bronchospasm and that use requires specialist oversight and alignment with FDA labeling and the clinical evidence base.

Term	Definition
{"text":"Baseline","status":""},{"text":"Defined as prior to receiving Nucala or another monoclonal antibody therapy for the listed condition.","status":""}
{"text":"Non-severe EGPA","status":""},{"text":"Vasculitis without life- or organ-threatening manifestations (examples: rhinosinusitis, asthma, mild systemic symptoms, uncomplicated cutaneous disease, mild inflammatory arthritis).","status":""}
{"text":"Month","status":""},{"text":"One month is equal to 30 days for authorization duration calculations.","status":""}
{"text":"Monoclonal antibody that may alter eosinophil levels","status":""},{"text":"Any monoclonal antibody therapy that may lower or otherwise change blood eosinophil counts; examples include Ebglyss (lebrikizumab-lbkz) and Nemluvio (nemolizumab-ilto) as noted in the policy.","status":""}

Revision History

9/1/2024title_change

Annual revision: updated coverage policy title from 'Mepolizumab' to 'Immunologicals - Nucala'.

12/15/2024criteria_revision

Selected revision: clarified eosinophil requirements for asthma to require ≥150 cells/µL either within the previous 6 weeks OR prior to treatment with a monoclonal antibody that may alter eosinophil levels; EGPA systemic corticosteroid criterion refined to 'currently receiving' for a minimum of 4 weeks; initial approval duration for EGPA changed to 9 months; examples Ebglyss and Nemluvio added as monoclonal antibody examples.

12/15/2024duration_change

Policy Summary

PayerCigna

PolicyImmunologicals - Nucala

Policy CodePolicy IP0422

Change TypeRevisions to indications, eosinophil timing, and approval durations (MODIFIED)

Effective Date

Next Review Date

Key ActionPrior Authorization is recommended for prescription benefit coverage of Nucala; approvals provided for specified durations (months defined as 30 days).

On This Page

Frequent severe exacerbations: two or more bursts of systemic corticosteroids in the previous year.

Serious exacerbation: at least one hospitalization, ICU stay, or mechanical ventilation in the previous year.

Failure of or inadequate response to optimized controller therapy: persistent uncontrolled disease despite adherence to high-dose ICS plus a second controller (and/or systemic corticosteroids) or disease that worsens when high-dose therapy is reduced.

Prior controller therapy: documentation of trials of appropriate inhaled/controller therapies as applicable (e.g., high-dose ICS/LABA with adherence optimization).

Prescribed by or in consultation with a pulmonologist or an allergist/immunologist (specialist).

Specialist documentation or consultation note required.

COPD — Initial Therapy

Age ≥ 18 years.
Peripheral blood eosinophil requirement: ≥ 300 cells/µL at screening or ≥ 150 cells/µL within the prior 12 months.
Background inhaled therapy (one of):
- Patient is currently receiving triple inhaled therapy (ICS + LAMA + LABA) for at least 3 months prior to request.
- Or documented contraindication or intolerance to inhaled corticosteroid (ICS) therapy, with alternative maintenance regimen described and rationale.
Exacerbation history: at least two moderate COPD exacerbations treated with systemic corticosteroids (with or without antibiotics) within the past year, OR at least one severe COPD exacerbation resulting in hospitalization (≥ 24 hours) within the past year.
Disease remains inadequately controlled despite background therapy as described above.
Prescribed by or in consultation with a pulmonologist (specialist).

CRSwNP — Initial Therapy

Age ≥ 18 years.
Diagnosis of chronic rhinosinusitis with nasal polyps confirmed by sinonasal endoscopy or CT scan showing sinonasal inflammation and polyps.
Symptoms persist despite at least 4 weeks of intranasal corticosteroid therapy or continuation of intranasal corticosteroid therapy as part of management.
Prior systemic/surgical therapy (one of):
- History of prior systemic corticosteroid use or prior sinonasal surgery for nasal polyps.
- Or documented contraindication to systemic corticosteroids or prior surgery, with rationale provided.
Inadequate response to standard therapies and high burden of disease despite intranasal corticosteroids.
Prescribed by or in consultation with an otolaryngologist (ENT) or allergy/immunology specialist.

EGPA — Initial Therapy

Age ≥ 18 years.
Active, non-severe disease (not immediately life- or organ-threatening).
Patient is receiving a stable dose of systemic corticosteroid therapy for at least 4 weeks prior to request.
Eosinophil timing/threshold (one of):
- Absolute peripheral blood eosinophil count ≥ 150 cells/µL within 4 weeks prior to request or prior to initiation of monoclonal antibody therapy.
- Documented prior absolute eosinophil count ≥ 1,000 cells/µL before monoclonal antibody therapy.
Prescribed by or in consultation with a rheumatologist, pulmonologist, or allergist/immunologist experienced in vasculitis management.

HES — Initial Therapy

Age ≥ 12 years.
Documented diagnosis of hypereosinophilic syndrome for ≥ 6 months without identifiable non-hematologic secondary cause.
FIP1L1-PDGFRα kinase negative status documented.
Exclusion of secondary causes of eosinophilia documented (e.g., parasitic infection, other secondary causes).
Baseline peripheral blood eosinophil count ≥ 1,000 cells/µL prior to initiation of monoclonal antibody therapy.
Prior trial of other HES therapies (e.g., systemic corticosteroids, immunosuppressive agents, or cytotoxic therapy) with inadequate response or intolerance; documentation of prior stable therapy for ≥ 4 weeks prior to request.
Prescribed by or in consultation with a hematologist or specialist experienced in HES management.

Required/appropriate specialists by indication: allergist, immunologist, pulmonologist, otolaryngologist (ENT), rheumatologist

Documentation Required

Prior Treatment and Trial Requirements

Prior treatment and trial requirements must be documented before approval. Include clinical details and duration of prior therapies in the request.

Asthma: documentation of trial of inhaled controller therapy (e.g., high-dose ICS plus other controllers) for ≥ 3 months
COPD: documentation of background triple inhaler therapy (ICS + LAMA + LABA) for at least 3 months
EGPA: documentation of ≥ 4 weeks of stable systemic corticosteroid therapy prior to initiation
HES: documentation of ≥ 4 weeks of stable alternative HES therapy (e.g., oral corticosteroids, immunosuppressive agents, or cytotoxic therapy) prior to initiation

Documentation Required

Eosinophil Test Timing and Result Documentation

Document peripheral blood eosinophil results with timing relative to the request. Eosinophil thresholds and timing requirements vary by indication; include lab date(s) with the value in the submission.

Required documentation: peripheral blood eosinophil level (absolute count) and date of testing
Timing: most indications require an eosinophil result within 4 weeks of the request OR documentation of an eligible prior eosinophil level obtained prior to monoclonal antibody therapy
Example monoclonal antibodies referenced in documentation: mepolizumab (Nucala), benralizumab (Fasenra), reslizumab

Denial Risk

Not Medically Necessary Uses

The following examples describe uses that are generally considered not medically necessary or are likely to be denied; include clear rationale when submitting requests for these scenarios.

Atopic dermatitis (not an FDA-approved indication for Nucala)
Concurrent use of another monoclonal antibody targeting the same pathway (e.g., simultaneous anti‑IL‑5 agents) — concurrent monoclonal antibody therapy
Eosinophilic gastrointestinal disorders (EGID) — not an established/covered indication in many benefit plans

Prior Authorization

COPD Prior Authorization Checklist

For COPD indications, prior authorization requires documentation of specific clinical criteria and therapies trialed. Ensure the checklist below is completed in the prior authorization submission.

Age: patient ≥ 18 years
Eosinophil level: documented blood eosinophil count meeting policy threshold (include date; see eosinophil documentation requirements)
Trial of inhaled therapies: documentation of background triple inhaler therapy (ICS + LAMA + LABA) for at least 3 months prior to request
Exacerbation history: at least two moderate exacerbations treated with systemic corticosteroids (with or without antibiotics) OR at least one severe exacerbation requiring hospitalization in the prior 12 months
Specialist involvement: documentation of care/consultation by an appropriate specialist (e.g., pulmonologist, allergist, immunologist)

Selected revision: asthma initial approval authorization duration changed from 12 months to 6 months; hypereosinophilic syndrome initial approval duration changed from 12 months to 8 months.

12/15/2024eosinophil_timing_clarified

Selected revision: eosinophil timing for EGPA clarified to require ≥150 cells/µL within the previous 4 weeks OR prior to treatment with a monoclonal antibody that may alter eosinophil levels (shortened from 6 weeks).

8/1/2025indication_addedLatest

Selected revision: Chronic Obstructive Pulmonary Disease (COPD) added as an FDA-approved indication with new approval criteria including age ≥18, eosinophil requirement (≥300 cells/µL), trial of inhaled therapies (including background triple therapy), exacerbation history, and specialist involvement; COPD removed from 'Conditions Not Recommended for Approval'.

2025-08-01eosinophil_timing_generalizedLatest

Context/administrative: policy defines eosinophil level timing across indications to require the test either within the previous 4 weeks OR prior to treatment with any monoclonal antibody therapy that may alter blood eosinophil levels (policy last reviewed 2025-08-01).