Alpha-1 proteinase inhibitors (Aralast NP™, Glassia®, Prolastin-C®, or Zemaira™) are used for chronic augmentation and maintenance therapy in adults with emphysema due to congenital deficiency of alpha-1 proteinase inhibitor (A1-PI), also known as alpha1-antitrypsin deficiency (A1AD).

Alpha-1 proteinase inhibitors (Aralast NP, Glassia, Prolastin-C, or Zemaira) administered intravenously may be considered medically necessary in individuals 18 years of age and older when ALL the following criteria are met: 

• Individual diagnosed with emphysema due to alpha-1 antitrypsin deficiency; and
• There is a documented high risk phenotype** resulting in a low serum concentration of alpha-1 antitrypsin (AAT), as evidenced by less than 80 mg per deciliter (mg/dL) (0.8 g/L) by radial immunodiffusion (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:
  • Presence of airflow obstruction is evidenced by forced expiratory volume (FEV1) less than or equal to 80% 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); or
• Individual has necrotizing panniculitis; and
• Initial authorization will be for a period of 12 months.

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

Reauthorization Criteria

• Continuation of therapy for AAT inhibitor therapy with Aralast NP, Glassia, Prolastin-C, or Zemaira may be considered medically necessary when ALL the following criteria are met:
  • Individual is currently receiving AAT inhibitor therapy; and
  • Provider attestation of positive clinical response; and
  • Reauthorization will be for a period of 12 months

The use of AAT inhibitor therapy (i.e. Aralast NP, Glassia, Prolastin-C, or Zemaira not meeting the criteria as indicated in this policy is considered not medically necessary.

Safety and effectiveness of alpha-1-proteinase inhibitors in pediatric individuals has not been established.

AAT inhibitor therapy (i.e. Aralast NP, Glassia, Prolastin-C, or Zemaira) may be considered medically necessary for individuals 18 years of age and older when applicable clinical criteria for individual medication policies are met and when administered in a physician’s office not affiliated with a hospital, specialized infusion centers not affiliated with a hospital or in the home.

Outpatient facility (Outpatient Hospital IV Infusion Department or Hospital-based Outpatient Clinical Level of Care) administration may be considered medically necessary if ANY of the following criteria are present to indicate the member is medically unstable for infusions in other than an outpatient facility setting:

• Member’s home is considered unsuitable for care by the home infusion provider; or
• Individual’s medical status requires enhanced monitoring beyond that which would routinely be needed for infusion therapy; or
• Previous severe adverse reaction (including but not limited to anaphylaxis, seizure, thromboembolism, myocardial infarction, renal failure) during or following administration of prescribed medication despite standard pre-medication; or
• Individual is receiving other medications that require close monitoring with a higher level of care (e.g., cytotoxic chemotherapy or blood products); or
• Individual is at high risk for complications due to medication administration (e.g., at risk for post-transplant complications, increased risk of infusion reactions due to presence of circulating antibodies, unstable vascular access, cardiopulmonary condition at risk for severe adverse reactions, unstable renal function with inability to safely tolerate IV volume loads, etc.); or 
• Individual is initiating therapy or re-initiating therapy after a period of at least 6 months with no therapy; or
• Physically and/or cognitively impaired AND a home caregiver is not available to comply with the required treatment regimen and schedule.

Home health services may be considered medically necessary when utilized for the administration of home infusion therapy and when provided by licensed eligible provider. Each case will be addressed on an individual basis.

The medications identified in this policy will be considered not medically necessary if administered in an unapproved hospital outpatient setting when an approved site of care is a viable option for treatment.

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Highmark may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits. 

Evidence-based guidelines support the administration of injectable medications in alternative sites of care such as the non-hospital physician’s office, non-hospital infusion center or in the home.  Administration of the injectable medications subject to this policy at alternate sites of care is based upon the professional judgment of the provider, and takes into account the clinical appropriateness for each individual member. Requests for administration of any dose of the drugs listed in this policy received from a hospital-based facility, physician’s office or specialized infusion center will be assessed for meeting the policy exception criteria based on the clinical documentation provided by the requesting practitioner.