Highmark Commercial Medical Policy - Pennsylvania

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Medical Policy: I-126-007
Topic: Alpha1-Proteinase Inhibitor Infusions
Section: Injections
Effective Date: May 28, 2018
Issue Date: May 28, 2018
Last Reviewed: February 2018

Prolastin C, Prolastin-C Liquid, Aralast NP™, Zemaira™, Glassia  are alpha1-proteinase inhibitors that are indicated for chronic augmentation and maintenance therapy administered intravenously weekly in adults with emphysema due to congenital deficiency of alpha1-proteinase inhibitor (A1-PI), also known as alpha1-antitrypsin deficiency (A1AD).

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Policy Position Coverage is subject to the specific terms of the member’s benefit plan.

Alpha-1 antitrypsin (A1AT) inhibitor augmentation therapy may be considered medically necessary for individuals with emphysema due to Alpha-1 antitrypsin deficiency (A1AD) when all the following criteria are met: 

  • The individual is 18 years of age or older; and
  • There is a documented high risk phenotype** resulting in a low serum concentration of Alpha 1 antitrypsin (A1AT), as evidenced by less than 80 mg per deciliter (mg/dL) (0.8 g/L) by radial immundiffusion (or less than 50 mg/dL (0.5 g/L) if measured by nephelometry) or less than 11 µM/L (35 % of normal); and
  • ONE of the following is present:
    • Moderate airflow obstruction is evidenced by forced expiratory volume (FEV1) of 30-65% of predicted value, prior to initiation of therapy; or
    • Individual has a rapid decline in lung function as measured by a change in FEV1 greater than 120 ml/year; and
  • The individual is a non-smoker or is a smoker undergoing active smoking cessation therapy; and
  • Must be on standard therapy for chronic obstructive pulmonary disease (COPD) (i.e. inhaled bronchodilators, inhaled steroids) as defined by current clinical guidelines (i.e. the Global Initiative COPD- GOLD guidelines); and
  • The individual is likely to be compliant with the prescribed protocol.  

** PiZZ, PiZ, or Pi phenotype (homozygous) or other phenotypes, (PiSZ or PiMS) when associated with serum AAT concentrations of less than 80 mg/dL. 

AAT inhibitor therapy (i.e. Prolastin C, Prolastin-C Liquid, Aralast NP, Zemaira, Glassia) is considered experimental/investigational and therefore non-covered when all of the above criteria are not met. The safety and/or effectiveness of the treatment cannot be established by review of the available published peer-reviewed literature. 

Procedure Codes
J0256, J0257

Repeat doses of AAT inhibitor therapy may be considered medically necessary for individuals who meet the clinical  requirements for AAT inhibitor at therapy initiation and who demonstrate a substantial reduction in the  rate of deterioration of lung function as evidenced by AAT levels greater than 80mg/dL(greater than 11 EM or greater than 0.8g/L).

Procedure Codes
J0256, J0257

Dosage recommendations per the FDA label.

Safety and effectiveness in pediatric patients has not been established.

Professional Statements and Societal Positions

Global initiative for Chronic Obstructive Lung Disease (GOLD).  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease.  Bronchodilators – Recommendations

  • For both beta2-agonists and anticholinergics, long-acting formulations are preferred over short-acting formulations.
  • The combined use of short- or long-acting beta2-agonists and anticholinergics may be considered if symptoms are not improved with single agents.
  • Based on efficacy and side effects inhaled bronchodilators are preferred over oral bronchodilators.
  • Based on evidence of relatively low efficacy and more side effects, treatment with theophylline is not recommended unless other long-term treatment bronchodilators are unavailable or unaffordable.

Place of Service: Outpatient

Experimental/Investigational (E/I) services are not covered regardless of place of service.

A1-PI infusion is typically an outpatient procedure which is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.

The policy position applies to all commercial lines of business

Denial Statements

Services that do not meet the criteria of this policy will be considered experimental/investigational (E/I). A network provider can bill the member for the experimental/investigational service. The provider must give advance written notice informing the member that the service has been deemed E/I. The member must be provided with an estimate of the cost and the member must agree in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.


  • Link to Provider Resource Center for the Medical Policy Update
  • 01/2018, Coverage Criteria Revised for Prolastin C®, Aralast NP™, Zemaira™, Glassia (alpha1-proteinase inhibitors infusions) Coverage Criteria Established for Prolastin-C Liquid
    03/2018, Coverage Criteria Revised for Alpha1-Proteinase Inhibitor Infusions

Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

Discrimination is Against the Law
The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer:
  • Provides free aids and services to people with disabilities to communicate effectively with us, such as:
    • Qualified sign language interpreters
    • Written information in other formats (large print, audio, accessible electronic formats, other formats)
  • Provides free language services to people whose primary language is not English, such as:
    • Qualified interpreters
    • Information written in other languages
If you need these services, contact the Civil Rights Coordinator.

If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:

U.S. Department of Health and Human Services
200 Independence Avenue, SW
Room 509F, HHH Building
Washington, D.C. 20201
1-800-368-1019, 800-537-7697 (TDD)

Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

Insurance or benefit/claims administration may be provided by Highmark, Highmark Choice Company, Highmark Coverage Advantage, Highmark Health Insurance Company, First Priority Life Insurance Company, First Priority Health, Highmark Benefits Group, Highmark Select Resources, Highmark Senior Solutions Company or Highmark Senior Health Company, all of which are independent licensees of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield plans.

Highmark retains the right to review and update its medical policy guidelines at its sole discretion. These guidelines are the proprietary information of Highmark. Any sale, copying or dissemination of the medical policies is prohibited; however, limited copying of medical policies is permitted for individual use.

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