CurrentColorado Rocky Mountain Health PlansPolicy 2025D0067J

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

Covers medical necessity and coverage criteria for alpha1-proteinase inhibitor augmentation therapy (Aralast NP, Glassia, Prolastin-C, Zemaira) for emphysema due to congenital alpha1-antitrypsin deficiency for Commercial members.

Policy Summary

PayerColorado Rocky Mountain Health Plans

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

Policy CodePolicy 2025D0067J

Change TypeClarified referencesarchived prior version

Effective DateNov 1, 2025

Next Review Date

Key ActionObtain prior authorization with documentation of genotype or confirmatory testing, serum AAT < 11 µmol/L, evidence of emphysema, and dosing per FDA labeling.

SourceLink

POLICY UPDATE CHANGES

Updated References section to reflect the most current information.

≤12 moInitial authorization interval

≤12 moReauthorization interval

11 µmol/LAAT threshold

J0256, J0257, E88.01Codes listed

0RCTs cited for emphysema progression

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.

Coverage Criteria for Alpha1-Proteinase Inhibitors

Initial Therapy

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

Initial therapy: Diagnosis of congenital alpha1-antitrypsin (AAT) deficiency confirmed by one of: Pi*ZZ, Pi*Z(null), Pi*(null)(null) phenotypes (homozygous), or other rare disease-causing AAT alleles associated with serum AAT < 11 µmol/L; circulating serum AAT concentration < 11 µmol/L (or stated assay equivalents: < 80 mg/dL by radial immunodiffusion or < 57 mg/dL by nephelometry); continued optimal conventional treatment for emphysema (e.g., bronchodilators, supplemental oxygen if necessary); patient is a current nonsmoker; diagnosis of emphysema confirmed with pulmonary function testing; dosing in accordance with FDA-approved labeling; initial authorization for no more than 12 months.< 11 µmol/L

Initial authorization interval ≤ 12 months

Continuation Therapy

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

Continuation therapy: Patient is currently receiving augmentation therapy for emphysema due to congenital AAT deficiency; documentation of positive clinical response (for example: decreased frequency of exacerbations, improvement in symptom burden, or slowed rate of FEV1 decline); patient remains a nonsmoker; dosing in accordance with FDA-approved labeling; reauthorization for no more than 12 months.

Reauthorization interval ≤ 12 months

Unproven / Not Established Indications

Not covered / considered unproven for the following indications:

Unproven indications: Conditions other than emphysema associated with AAT deficiency; cystic fibrosis; and other non-COPD conditions (e.g., refractory bronchial asthma, fibromyalgia, panniculitis, vasculitis) where evidence is limited to case reports or small studies.

Use for these indications is considered unproven or not medically necessary absent supporting evidence

Labeled Indication Coverage

Covered when ALL of the following are met

FDA-labeled indication: Prescribed as chronic augmentation therapy for patients with congenital deficiency of alpha1-proteinase inhibitor (A1-PI) who have clinically evident emphysema; documentation must support congenital A1-PI deficiency and clinical emphysema.

Coverage aligned to FDA labeling; randomized controlled trials demonstrating effect on emphysema progression are not available

Miscellaneous/Off-label Uses

Off-label/compassionate uses

Other indications: Case reports describe compassionate use of A1-PI augmentation for refractory bronchial asthma, fibromyalgia, panniculitis, and vasculitis with reported positive responses, but evidence is limited to case reports and larger studies are needed to establish efficacy.

Evidence insufficient to support routine coverage for these off-label indications

Alpha1-proteinase inhibitors are not indicated for treatment of lung disease in patients without established congenital A1-PI (AAT) deficiency. FDA-labeled products (Aralast NP, Prolastin-C, Glassia, Zemaira) are approved specifically for chronic augmentation therapy in patients with documented congenital A1-PI deficiency and clinically evident emphysema; use outside that labeled population is not an FDA-indicated use and may be denied.

Alpha1-proteinase inhibitors are not indicated for treatment of lung disease in patients in whom congenital A1-PI deficiency has not been established. The FDA notes these agents are labeled for augmentation therapy only in patients with documented congenital A1-PI deficiency and clinically evident emphysema.

Use of alpha1-proteinase inhibitor for conditions other than emphysema associated with AAT deficiency, including cystic fibrosis, is considered unproven. Small trials and case reports (for example, short-duration CF studies showing biomarker changes without lung function benefit) suggest possible biological effects, but larger studies with clinically relevant endpoints are required before such indications can be considered medically necessary.

Use of alpha1-proteinase inhibitors for lung disease without documented congenital A1-PI deficiency is not an indicated use per the FDA labeling and lacks evidence of benefit. Requests for therapy in patients who do not have confirmed congenital deficiency should be considered not medically necessary and are at risk for denial.

Coding and Products

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

FDA-labeled products mentionedmixed

Aralast NP	FDA-labeled alpha1-proteinase inhibitor (human) product name
Prolastin-C	FDA-labeled alpha1-proteinase inhibitor (human) product name
Glassia	FDA-labeled alpha1-proteinase inhibitor (human) product name
Zemaira	FDA-labeled alpha1-proteinase inhibitor (human) product name

Serum AAT concentration threshold

Serum AAT concentration threshold< 11 µmol/L (equivalent to < 80 mg/dL by radial immunodiffusion or < 57 mg/dL by nephelometry)

Alternate units provided< 80 mg/dL by radial immunodiffusion

Alternate units provided< 57 mg/dL by nephelometry

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization required for FDA-labeled chronic augmentation therapy of emphysema due to congenital alpha1-proteinase inhibitor (A1-PI/AAT) deficiency. Initial approvals are limited to no more than 12 months; reauthorization (continuation) approvals are also limited to no more than 12 months.

Initial and continuation therapy require prior authorization
Initial authorization duration: ≤ 12 months
Reauthorization/continuation duration: ≤ 12 months

Denial Risk

Denial Triggers

Requests will be denied when criteria are not met. Common denial triggers include lack of documentation of an established congenital A1-PI (AAT) deficiency (e.g., phenotype/genotype and low serum AAT level), dosing that is inconsistent with FDA-approved labeling, requests for use in patients without clinically evident emphysema due to AAT deficiency, or use in IgA-deficient patients with anti-IgA antibodies.

Background and Rationale

Alpha1-antitrypsin (A1-PI) deficiency is an autosomal co-dominant disorder resulting in reduced circulating AAT levels and consequent excess neutrophil elastase activity, which predisposes to early-onset panacinar emphysema. Augmentation therapy with human plasma–derived A1-PI aims to restore serum and epithelial lining fluid AAT levels and may slow decline in lung function in selected patients, particularly those with documented congenital deficiency and appropriate clinical features.

Definitions

Severe AAT deficiency

Definition example genotypesPi*ZZ, Pi*Z(null), Pi*(null)(null) (homozygous) or other rare disease‑causing alleles

Associated serum levelSerum AAT level < 11 µmol/L

Clinical consequenceAssociated with severe AAT deficiency leading to increased neutrophil elastase activity and emphysema

Alpha1‑proteinase inhibitor (A1‑PI)

What it isHuman plasma‑derived alpha1‑proteinase inhibitor (also called alpha1‑antitrypsin) used for augmentation therapy

Indication per FDA/policyChronic augmentation therapy for congenital A1‑PI (AAT) deficiency with clinically evident emphysema

Policy Revision History

2025-11-01updateLatest

Updated References section to reflect the most current information; archived previous policy version 2024D0067I.