CurrentUnitedHealthcarePolicy 2025D0067J

Alpha1-Proteinase Inhibitors (A1-PI) for AAT Deficiency

Covers UnitedHealthcare commercial medical benefit policy for use of plasma-derived alpha1-proteinase inhibitors (Aralast NP, Glassia, Prolastin-C, Zemaira) for chronic augmentation/maintenance therapy of emphysema due to congenital alpha1-antitrypsin (AAT) deficiency; applies to providers administering these therapies under the commercial plan.

Policy Summary

PayerUnitedHealthcare

PolicyAlpha1-Proteinase Inhibitors (A1-PI) for AAT Deficiency

Policy CodePolicy 2025D0067J

Change TypeNo material changes

Effective DateNov 1, 2025

Next Review Date

Key ActionObtain prior authorization and document diagnosis (specified Pi phenotype or disease-causing alleles), serum AAT < 11 µmol/L, evidence of emphysema, nonsmoker status, and adherence to FDA dosing.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

<= 12initial auth max

<= 12reauth max

2listed drug codes

E88.01diagnosis code

4FDA products

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Coverage Criteria for Alpha1-Proteinase Inhibitors

Initial Therapy

Covered when ALL of the following are met for initial therapy:

Diagnosis of congenital AAT deficiency: Diagnosis of congenital alpha1-antitrypsin (AAT) deficiency confirmed by one of the following: Pi*ZZ, Pi*Z(null), or Pi*(null)(null) protein phenotypes (homozygous); or other rare AAT disease-causing alleles associated with AAT level < 11 µmol/L.AAT < 11 µmol/L or specified phenotypes

Serum AAT level: Circulating serum concentration of alpha1-antitrypsin (AAT) level < 11 µmol/L (corresponding to < 80 mg/dL by radial immunodiffusion or < 57 mg/dL by nephelometry).< 11 µmol/L

mg/dL equivalents provided

Conventional treatment: Patient is receiving continued optimal conventional treatment for emphysema (e.g., bronchodilators, supplemental oxygen if necessary).

Smoking status: Patient is a current nonsmoker.

Emphysema confirmation: Diagnosis of emphysema confirmed with pulmonary function testing.

Dosing must be in accordance with United States Food and Drug Administration approved labeling.

Initial authorization duration: Initial authorization will be for no more than 12 months.<= 12 months

Continuation Therapy

Covered when ALL of the following are met for continuation therapy:

Current therapy: Patient is currently receiving therapy for emphysema due to congenital alpha1-antitrypsin (AAT) deficiency.

Clinical response: Documentation of a positive clinical response (e.g., decreased frequency of exacerbations, improvement in symptom burden, slowed rate of FEV1).

Smoking status: Patient remains a nonsmoker.

Dosing must be in accordance with United States Food and Drug Administration approved labeling.

Reauthorization duration: Reauthorization will be for no more than 12 months.

Covered Indication and Limitations

Coverage stance and limits for FDA-labeled A1-PI products

FDA Indication Requirements: Product must be an FDA-labeled alpha1-proteinase inhibitor for chronic augmentation therapy in patients having congenital deficiency of alpha1-proteinase inhibitor (A1-PI) with clinically evident emphysema.

FDA indication statement from product labeling

Clinical evidence limitations: Effects on pulmonary exacerbations and on the progression of emphysema in AAT deficiency have not been demonstrated in randomized, controlled clinical trials; clinical data demonstrating long-term effects are not available.

Informational for clinical context and coverage expectations

Contraindications and safety: Products are derived from pooled human plasma and may carry a risk of transmitting infectious agents; Aralast NP, Glassia, Prolastin-C, and Zemaira are contraindicated in IgA-deficient patients with antibodies against IgA.

Safety information may affect coverage decisions

Use of alpha1-proteinase inhibitors outside their FDA-labeled indication is considered unproven. Specifically, augmentation therapy with plasma-derived alpha1-proteinase inhibitors is not supported by adequate evidence for conditions other than emphysema associated with congenital alpha1-antitrypsin (AAT) deficiency. Requests for coverage for such indications should be evaluated in light of the limited clinical data and the policy’s explicit exclusion for non‑emphysema uses.

Alpha1-proteinase inhibitors are not indicated for treatment of lung disease in patients in whom congenital A1-PI (AAT) deficiency has not been established. Coverage is limited to patients who meet diagnostic criteria for congenital AAT deficiency and have clinically evident emphysema as described in this policy.

Augmentation therapy with alpha1-proteinase inhibitor is considered unproven for disorders other than emphysema due to congenital AAT deficiency. The policy limits coverage to the FDA‑labeled population—patients with congenital A1‑PI deficiency and clinically evident emphysema—because efficacy for other conditions has not been established in randomized controlled trials or supported by robust long‑term data.

Examples of conditions for which A1-PI augmentation is unproven include refractory bronchial asthma, fibromyalgia, panniculitis, and vasculitis. Published reports for these conditions are limited to case reports or small compassionate‑use series, and authors have concluded that further laboratory and larger clinical trials are needed before efficacy can be determined.

Applicable Codes and Diagnostic Thresholds

Applicable Codesmixed

J0256	Injection, alpha 1-proteinase inhibitor, human, 10 mg, not otherwise specified.
J0257	Injection, alpha 1-proteinase inhibitor (human), (Glassia), 10 mg
E88.01	Alpha-1-antitrypsin deficiency

HCPCS CodesHCPCS

J0256	Injection, alpha 1-proteinase inhibitor, human, 10 mg, not otherwise specified.
J0257	Injection, alpha 1-proteinase inhibitor (human), (Glassia), 10 mg

Diagnosis CodesICD-10

E88.01

Alpha-1-antitrypsin deficiency

inv-09: Serum alpha1-antitrypsin level thresholds

Serum AAT threshold (primary)Circulating serum alpha1-antitrypsin (AAT) concentration < 11 µmol/L

Radial immunodiffusion equivalent< 80 mg/dL when measured by radial immunodiffusion

Nephelometry equivalent< 57 mg/dL when measured by nephelometry

Measurement contextAAT level requirement applies as part of initial therapy diagnostic criteria and must be documented in provider submission

Prior Authorization, Documentation, and Utilization Management

Prior Authorization

Prior Authorization Required; Duration Limits

Prior authorization is required for initiation and continuation of alpha1-proteinase inhibitor therapy. Initial authorization will be limited to no more than 12 months. Reauthorization (continuation) approvals will also be issued for no more than 12 months per authorization period.

Initial and reauthorization limits: up to 12 months
Prior authorization required before dispensing or administration

Prior Authorization

Verify Member Plan and Prior Authorization Requirements

Providers must verify member-specific benefit plan requirements and confirm medical necessity prior to prescribing or administering therapy. Coverage is determined by the member's benefit plan document and applicable federal or state mandates; in case of conflict, the member-specific plan governs.

Verify eligibility and benefits with UnitedHealthcare prior to treatment
Confirm plan-specific prior authorization processes and forms

Definitions and Diagnostic Phenotypes

inv-19: Diagnostic phenotype/thresholds

Diagnostic phenotypes (homozygous)Pi*ZZ, Pi*Z(null), or Pi*(null)(null) protein phenotypes

Other disease-causing allelesOther rare AAT disease-causing alleles associated with serum AAT level < 11 µmol/L (e.g., Pi Malton)

Serum threshold linked to phenotypeDiagnosis requires association with circulating AAT < 11 µmol/L (equivalents: < 80 mg/dL by radial immunodiffusion or < 57 mg/dL by nephelometry)

inv-20: Alpha1-proteinase inhibitor definition

Product descriptionHuman plasma-derived alpha1-proteinase inhibitor (A1-PI; alpha1-antitrypsin) used for chronic augmentation therapy

Intended use (FDA-labeled)Chronic augmentation therapy in patients with congenital A1-PI (AAT) deficiency and clinically evident emphysema

Background on Alpha1-Antitrypsin Deficiency

Alpha1-antitrypsin (AAT) deficiency is an inherited, co‑dominant disorder characterized by reduced circulating AAT levels that permit unopposed neutrophil elastase activity and progressive destruction of lung parenchyma. Plasma‑derived alpha1-proteinase inhibitor (A1-PI) products (Aralast NP, Prolastin‑C, Glassia, Zemaira) are approved by the FDA for chronic augmentation therapy in patients with congenital AAT deficiency and clinically evident emphysema. The therapeutic rationale is to restore deficient AAT levels to protect the lower respiratory tract from proteolytic damage. However, clinical trials have not demonstrated effects on pulmonary exacerbations or emphysema progression in randomized controlled studies, and long‑term outcome data are limited. Safety considerations include that these products are derived from pooled human plasma (theoretical risk of infectious transmission) and are contraindicated in IgA‑deficient patients with anti‑IgA antibodies.