Find policies, billing codes, payers, states, and providers
Alpha 1-Proteinase Inhibitors
Customize your policy alerts
Sign up for Aetna Policy 0145 alerts
Get alerted when Policy 0145 changes without checking for updates manually.
Monitor payer policy activity
This policy governs medical necessity, precertification, and coverage criteria for alpha 1‑proteinase inhibitor therapy (Aralast NP, Glassia, Prolastin‑C, Zemaira) for treatment of emphysema due to alpha1‑antitrypsin deficiency in Aetna commercial medical plans.
No material clinical or coverage changes in this revision.
Coverage Criteria
Initial Therapy
Covered when ALL of the following are met:
All four conditions required
Continuation Therapy
Covered when ALL of the following are met:
Ongoing benefit must be documented
Coverage stance — investigational and established therapies (descriptive)
Investigational and emerging therapies described (no explicit coverage criteria stated):
Replacement therapy with alpha‑1 proteinase inhibitor is considered experimental and investigational when used in individuals who do not have clinical evidence of emphysema. The policy rationale notes that panacinar emphysema does not develop in some persons with alpha‑1 antitrypsin (AAT) deficiency, and in those without clinical emphysema replacement therapy has no proven value and is therefore not an established indication.
Inhaled formulations of alpha‑1 antitrypsin have demonstrated biochemical activity and short‑term safety in small studies, but their clinical effectiveness and impact on long‑term outcomes remain unproven. Short randomized phase IIa studies showed that inhaled alpha‑1 preparations can increase sputum AAT and are generally well tolerated, yet there is a lack of adequately powered phase II/III trials with clinical end points (lung function, imaging, exacerbations, health status, mortality) to establish long‑term benefit.
Aetna applies a brand‑preference rule for plasma‑derived augmentation products: Aralast NP, Glassia, and Zemaira are regarded as medically necessary only when the member has a documented contraindication, intolerance, or an ineffective trial of the lower‑cost alternative Prolastin‑C. The policy states there is insufficient evidence to show these branded products are superior to Prolastin‑C for augmentation/maintenance therapy.
Inhaled alpha‑1 antitrypsin preparations are designated investigational. While aerosol delivery can increase local airway AAT levels and short‑term studies report established safety and biochemical efficacy, the policy emphasizes that inhaled therapy’s effectiveness for chronic clinical outcomes has not been established and additional larger, longer randomized trials are required before inhaled formulations can be considered standard therapy.
Coding
| J0256 | Injection, alpha 1 - proteinase inhibitor - (human), not otherwise specified, 10 mg. |
| J0257 | Injection, alpha 1 proteinase inhibitor - (human), (glassia), 10 mg. |
| S9346 | Home infusion therapy, alpha-1-proteinase inhibitor (e.g., Prolastin); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem. |
| 38204 | Management of recipient hematopoietic progenitor cell donor search and cell acquisition [ alpha-1 antitrypsin deficiency gene therapy]. |
| E88.01 | Alpha-1-antitrypsin deficiency [only covered when billed with panlobular emphysema]. |
| J43.1 | Panlobular emphysema [panacinar emphysema]. |
| D80.2 | Selective deficiency of immunoglobulin A [IgA deficient with IgA antibodies]. |
| E84.0-E84.9 | Cystic fibrosis. |
| J80 | Acute respiratory distress syndrome. |
| T86.90-T86.99 | Complication of unspecified transplanted organ and tissue. |
| No codes listed |
Provider Actions & Requirements
Precertification / Prior Authorization Required
Precertification of alpha 1-proteinase inhibitors (Aralast NP, Glassia, Prolastin-C, and Zemaira) is required for all Aetna participating providers and members in applicable plan designs. Call (866) 752-7021 or fax (888) 267-3277 for precertification. Statement of Medical Necessity (SMN) precertification forms are available via Specialty Pharmacy Precertification. Site of Care Utilization Management Policy applies for infusions.
Prior Authorization — None Specified (Informational)
No additional payer-specific prior authorization algorithms or step-therapy sequences beyond the precertification and brand-preference rule are specified in this excerpt. There are no explicit prior authorization conditions described other than the general precertification requirement.
- No separate prior authorization forms or extra PA pathways specified in this excerpt
- Informational: CPT/HCPCS/ICD-10 code lists provided but PA specifics not further detailed
Administrative / Contact / Reference Information
This section contains administrative and reference information (policy history, review dates, and references/prescribing information). No explicit denial triggers are listed in this excerpt; however, lack of required precertification may result in claim delay or denial per plan rules.
- Policy effective date: 07/17/1996; Last review: 04/25/2023; Next review: 02/22/2024
- References and prescribing information cited (e.g., Aralast NP, Zemaira, Baxalta/CSL prescribing information)
- Administrative note: Clinical Policy Bulletins are informational and subject to change
Brand Selection / Step
Brand-preference rule: Prolastin-C is the lower-cost preferred product. Aralast NP, Glassia, and Zemaira are considered medically necessary only when the member has a contraindication, intolerance, or inadequate response to Prolastin-C.
- Preferred agent: Prolastin-C (use required unless contraindicated/intolerant/ineffective)
- Alternatives (allowed if Prolastin-C contraindicated/intolerant/ineffective): Aralast NP, Glassia, Zemaira
Required Clinical Documentation
Required clinical documentation to support medical necessity includes pretreatment serum AAT level, pretreatment post-bronchodilation FEV1, and genotype/phenotype confirming severe deficiency. Continuation of therapy requires evidence of clinical benefit.
- Pretreatment serum AAT level < 11 micromol/L (80 mg/dL by radial immunodiffusion or 50 mg/dL by nephelometry)
- Pretreatment post-bronchodilation FEV1 between ≥25% and ≤80% predicted
- Documented genotype/phenotype consistent with severe deficiency (e.g., PiZZ, PiZ null, homozygous null)
- Exclusion: PiMZ or PiMS phenotypes not eligible
- Continuation: documentation of beneficial clinical response
No Step Therapy / References
No step therapy algorithms, required prior failures, or explicit denial triggers are described in this excerpt beyond the brand-preference requirement and the precertification requirement. References and prescribing information cited in the policy may be used to support clinical decision-making and documentation.
Background
Alpha‑1 antitrypsin (AAT) is a circulating plasma antiprotease that inhibits neutrophil elastase. Congenital deficiency of AAT (AATD, due to SERPINA1 mutations) reduces protection against proteolytic lung injury and is associated with early‑onset panacinar emphysema. Replacement augmentation therapy with plasma‑derived alpha‑1 proteinase inhibitors is intended to restore protective levels of AAT in plasma and lung and is used for lifelong augmentation in adults with clinically evident emphysema due to severe AAT deficiency. The policy also notes important safety considerations, including contraindication in patients with IgA deficiency with anti‑IgA antibodies because of anaphylaxis risk, and defines the protective plasma threshold as AAT < 11 μM (equivalent values by common assays are cited elsewhere in the policy).
Definitions
Initial Therapy Criteria
Initial Therapy
Initial therapy — clinical entry criteria (detailed):
Initial therapy — investigational formulations
Investigational formulations and delivery strategies (descriptive):
Continuation of Therapy Criteria
Continuation of Therapy
Continuation of therapy — coverage requirements:
Ongoing benefit must be documented in the medical record
Continuation therapy — safety observations and long‑term repeat dosing notes
Continuation therapy — safety observations and long‑term dosing notes:
Step Therapy
| Step | Preferred agent | Non-preferred agents | Requirement / Failure criteria |
|---|---|---|---|
| 1 | Prolastin-C | Aralast NP; Glassia; Zemaira | Aralast NP, Glassia, and Zemaira are considered medically necessary only if the member has a contraindication, intolerance, or ineffective trial to lower‑cost Prolastin‑C. |
| Step | Description | Notes / References | Requirement / Failure criteria |
|---|---|---|---|
| [{"text":"1","status":""},{"text":"No formal step therapy algorithm specified in these sections; content provides background and citations regarding investigational and established therapies (gene therapy, inhaled AAT, PEGylated/recombinant constructs).","status":""},{"text":"Policy references and background citations (selected): Abboud et al.; Chiuchiolo & Crystal; CSL Behring Zemaira PI; Franciosi et al.; Gaggar et al.","status":""},{"text":"No step therapy requirements are stated in the cited background/references. | |||
| status":""}] |
Site of Care
Follow Aetna Site of Care policy for infusions
Site of Care Utilization Management Policy applies to specialty drug infusions; follow Aetna's site‑of‑service policy for alpha1‑proteinase inhibitor infusions whether provided in an infusion center or at home.
- Adhere to Utilization Management Policy on Site of Care for Specialty Drug Infusions
Site of care and routes: IV established; others investigational
Routes under study include intravenous, intrapleural, intramuscular gene transfer, and inhalation; established augmentation therapy is administered by weekly intravenous infusion in infusion center, home, or hospital outpatient settings.
- Established augmentation: weekly IV infusion
- Investigational/under study: intrapleural, intramuscular gene transfer, inhalation (clinic/home)
Revision History & Administrative
Administrative/contact information and policy notices
Policy history and administrative contact details (including review dates and the Clinical Policy Bulletin notice) are listed to assist providers in locating updates and supplemental information.
- See Policy History for review dates and links to definitions and additional information
- Clinical Policy Bulletin Notes available for administrative assistance
OpenPayer is powered by Trek Health's payer performance platform. Trek continuously ingests, validates, and normalizes Transparency in Coverage data alongside payer policies and other commercial payer data to create a structured payer intelligence foundation. OpenPayer uses this foundation to deliver personalized search results, dynamically generated policy pages, and tailored policy monitoring based on each user's payers, specialties, billing codes, and areas of interest. The same intelligence powers broader payer performance workflows, including reimbursement benchmarking, contract evaluation, payer negotiations, and financial decision-making.