CurrentUnitedHealthcarePolicy CS2026D0067P

Alpha1-Proteinase Inhibitors

Defines UnitedHealthcare Community Plan medical benefit drug policy for human alpha1-proteinase inhibitors used as chronic augmentation and maintenance therapy for emphysema due to congenital alpha1-antitrypsin (AAT/A1-PI) deficiency. Includes initial and continuation criteria, applicable HCPCS/J-codes and diagnosis code(s), exclusions, dosing conformity requirement, and authorization durations.

Policy Summary

PayerUnitedHealthcare

PolicyAlpha1-Proteinase Inhibitors

Policy CodePolicy CS2026D0067P

Change TypeTemplate Update (removed Louisiana-specific content)

Effective DateApr 1, 2026

Next Review Date

Key ActionInitial authorization is limited to no more than 12 months and requires documentation of genotype/allele confirmation, serum AAT < 11 µmol/L (or equivalent), PFT-confirmed emphysema, evidence of continued conventional therapy, nonsmoker status, and dosing per FDA label.

POLICY UPDATE CHANGES

Template Update; removed content/language pertaining to the state of Louisiana.

4FDA-labeled products referenced

2Named HCPCS J-codes

12Authorization duration (months)

<11Required serum AAT threshold (µmol/L)

Coverage Summary & Scope

Defines UnitedHealthcare Community Plan medical benefit drug policy for human alpha1-proteinase inhibitors (Aralast NP, Glassia, Prolastin-C, Zemaira) for chronic augmentation and maintenance therapy of emphysema due to congenital alpha1-antitrypsin (AAT/A1-PI) deficiency. Coverage is covered with criteria when all specified initial or continuation criteria are met. The policy effective date is April 1, 2026.

Key thresholds and authorization

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

Authorization duration (initial/reauthorization)12 months / 12 months

Named HCPCS J-codesJ0256, J0257

FDA-labeled products referencedAralast NP, Glassia, Prolastin-C, Zemaira (4)

Initial Therapy Criteria

Initial Therapy

Covered when ALL of the following are met:

ALL of the following

Diagnosis of congenital alpha1-antitrypsin deficiency confirmed by one of the following:
- ONE of
  - Pi*ZZ, Pi*Z(null), or Pi*(null)(null) protein phenotypes (homozygous)
  - Other rare AAT deficiency disease-causing alleles associated with serum AAT level < 11 µmol/L (e.g., Pi (Malton, Malton))< 11 µmol/L
Circulating serum concentration of AAT < 11 µmol/L (which corresponds to < 80 mg/dl if measured by radial immunodiffusion or < 57 mg/dl if measured by nephelometry)< 11 µmol/L (equivalent to < 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)
Current nonsmoker
Diagnosis of emphysema confirmed with pulmonary function testing
Dosing is in accordance with the United States Food and Drug Administration approved labeling
Initial authorization will be for no more than 12 months
Authorization duration limit

(See individual child criteria)

Continuation Therapy Criteria

Continuation of Therapy

Covered when ALL of the following are met:

ALL of the following

Patient is currently receiving therapy for emphysema due to congenital alpha1-antitrypsin (AAT) deficiency
Documentation of a positive clinical response (e.g., decreased frequency of exacerbations, improvement in symptom burden, slowed rate of FEV1)
Patient remains a nonsmoker
Dosing is in accordance with the United States Food and Drug Administration approved labeling
Reauthorization will be for no more than 12 months
Reauthorization duration limit

(See individual child criteria)

Not Medically Necessary / Unproven Indications

Not Medically Necessary / Unproven

Alpha1-proteinase inhibitors are unproven for the following:

ANY of the following

Conditions other than emphysema associated with alpha1-antitrypsin deficiency
Cystic fibrosis

(See individual child criteria)

State-specific exceptions remain in effect for Arizona, Indiana, Kansas, North Carolina, Ohio, and Washington per the policy application; the 04/01/2026 template update removed Louisiana-specific content.

Prior Authorization, Documentation & Billing Rules

Prior Authorization

Initial authorization requirement

Initial authorization is limited to no more than 12 months and requires documentation of genotype/allele confirmation (e.g., Pi*ZZ or other disease-causing alleles), circulating serum AAT concentration < 11 µmol/L (or the listed equivalents), confirmation of emphysema by pulmonary function testing, evidence of continued optimal conventional therapy for emphysema, current nonsmoker status, and dosing in accordance with the U.S. FDA–approved labeling. Affected codes: J0256, J0257.

J0256
J0257

Prior Authorization

Reauthorization/Continuation

Reauthorization/continuation is limited to no more than 12 months and requires documentation that the patient is currently receiving therapy for emphysema due to congenital AAT deficiency, documentation of continued clinical benefit (for example, decreased exacerbations, symptom improvement, or slowed FEV1 decline), the patient remains a nonsmoker, and dosing is in accordance with U.S. FDA–approved labeling. Affected codes: J0256, J0257.

J0256
J0257

Documentation Required

Diagnostic confirmation required

Providers must document genotype/allele status (for example, PiZZ or other disease‑causing alleles) and objective confirmation of emphysema by pulmonary function testing. This diagnostic confirmation (genotype/allele and PFT evidence) must be included in the medical record.

Billing Rule

Dosing per FDA labeling

Dosing must be in accordance with the FDA‑approved labeling for the specific product; claims may be reviewed for adherence to approved dosing.

J0256
J0257

Clinical Evidence Summary

47.6Mean FEV1 change mL/yr favoring augmentation (Tonellis) (p=0.05)

34.2 vs 49.2FEV1 decline lower during treatment period (mL/yr), retrospective cohort (p=0.019)

RR 0.64Registry: augmentation associated with decreased mortality (95% CI 0.43-0.94, p=0.02)

A1-PI augmentation therapy increases serum and lung AAT levels and is intended to correct the imbalance between neutrophil elastase and protease inhibitors, theoretically protecting the lower respiratory tract. Randomized trial evidence demonstrating effects on pulmonary exacerbations and progression of emphysema is limited or lacking.

Observational cohort and registry studies report slowed decline in FEV1 and suggest a potential survival benefit: cohort and nonrandomized studies showed smaller annual FEV1 declines during treatment periods and an observational registry reported lower mortality associated with augmentation (risk ratio 0.64, 95% CI 0.43–0.94).

Background & Definitions

Alpha1-antitrypsin (AAT) deficiency is an inherited, co-dominant disorder characterized by reduced A1-PI levels and increased neutrophil elastase activity that leads to destruction of lung connective tissue and emphysema. Human A1-PI augmentation therapy increases circulating and lung AAT, restores antiprotease capacity, and is FDA-labeled for chronic augmentation in patients with congenital AAT deficiency and clinically evident emphysema.

Clinical studies demonstrate biochemical reversal of deficiency in blood and lung fluid and observational data suggest slowing of FEV1 decline in some cohorts, although randomized trials have not demonstrated effects on exacerbations or emphysema progression.

Term	Definition
{"text":"AAT / A1-PI","status":""},{"text":"Alpha1-antitrypsin / Alpha1-proteinase inhibitor, a plasma protein that inhibits neutrophil elastase.","status":""}
{"text":"PiZZ","status":""},{"text":"Homozygous Z allele protein phenotype associated with severe AAT deficiency.","status":""}

Policy Summary

PayerUnitedHealthcare

PolicyAlpha1-Proteinase Inhibitors

Policy CodePolicy CS2026D0067P

Change TypeTemplate Update (removed Louisiana-specific content)

Effective DateApr 1, 2026

Next Review Date

On This Page

OpenPayer

Alpha1-Proteinase Inhibitors

Coverage Summary & Scope

Initial Therapy Criteria

Continuation Therapy Criteria

Not Medically Necessary / Unproven Indications

Applicable Codes

Prior Authorization, Documentation & Billing Rules

Clinical Evidence Summary

Background & Definitions

Policy Revision History

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