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.

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. 

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).

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.

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

• Link to Diagnosis Codes

• Link to References