00053-7201-XX Zemaira 1000 MG SOLR (CSL BEHRING)
00944-2814-XX Aralast NP 500 MG SOLR (BAXALTA)
00944-2815-XX Aralast NP 1000 MG SOLR (BAXALTA)
00944-2884-XX Glassia 1000 MG/50ML SOLN (BAXALTA)
13533-0700-XX Prolastin-C 1000 MG SOLR (GRIFOLS USA)
13533-0703-XX Prolastin-C 1000 MG SOLR (GRIFOLS USA)
13533-0705-XX Prolastin-C 1000 MG/20ML SOLN (GRIFOLS USA)
The release of proteolytic enzymes such as trypsin and elastin through the blood onto organ surfaces and into tissue spaces results in tissue damage by a “digestive” process unless inhibitors are present. Alpha-1-antitrypsin (AAT), produced in the liver, is the most abundant of these serum protease inhibitors. Also known as alpha1-proteinase inhibitor, it blocks the destructive action of trypsin and elastin as well as several other proteases.
While rare, the congenital condition of AAT deficiency is associated with the development of emphysema at an unusually early age and other conditions including increased incidence of neonatal hepatitis, usually progressing to cirrhosis. Normal reference values AAT 100-190 mg/dL with AAT Proteotype negative for S and Z phenotype (Non S Non Z) (Mayo Clinic). Some rare cases may have AAT levels of zero. All individuals with AAT serum levels <70 mg/dL may have a homozygous deficiency and are at risk for early lung disease.
Alpha-1-antitrypsin prototyping should be done to confirm the presence of homozygous deficiency alleles. Individuals who are severely deficient are typically homozygous in the Z allele with AAT levels 20 to 30% of normal. Affected persons are extremely susceptible to cigarette smoking and may develop emphysema at an early age. The form of emphysema is characteristically the panacinar type with predominant basal distribution.
Treatment of panacinar emphysema due to AAT deficiency with an alpha1-proteinase inhibitor is a process of chronic augmentation and maintenance therapy. The products are prepared from pooled human plasma and purified to remove virus and DNA fragments. The theoretical intent of augmentation is to protect the lower respiratory tract by correcting the imbalance between neutrophil elastase and protease inhibitors; however this has not been proven in any clinical trials. Blood levels of circulating alpha1-proteinase inhibitor were found to increase after treatment.
Alpha1-proteinase inhibitor therapy is considered medically necessary for the treatment of emphysema if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Alpha1-proteinase inhibitor therapy for the treatment of other conditions/diseases, including, but not limited to, the following is considered investigational:
Lung disease without congenital alpha-1-antitrypsin (A1A) deficiency
Alpha1-proteinase inhibitor therapy is considered medically appropriate if ALL of the following criteria are met:
Diagnosis of emphysema due to alpha-1-antitrypsin (AAT) deficiency
Individual is 18 years of age or older
Individual has an FEV1 in the range of 30-65% of predicted
Individual has alpha-1-antitrypsin (AAT) deficiency with PiZZ, PiZ (null), or Pi (null, null) phenotypes
Individual has AAT deficiency and clinical evidence of panacinar/panlobular emphysema
Individual has low serum concentration of AAT ≤ 11 μM/L or ≤ 80 mg/dL (if measured by radial immunodiffusion) or ≤ 50 mg/dL (if measured by nephelometry)
Individual is receiving optimal medical therapy (e.g., comprehensive case management, pulmonary rehabilitation, vaccinations, smoking cessation, self-management skills, etc.)
Individual is not a tobacco smoker
Alpha1-proteinase inhibitor therapy for renewal is considered medically appropriate if ALL of the following criteria are met:
Individual continues to meet the initial approval criteria
Disease response with treatment as defined by elevation of AAT levels above baseline, substantial reduction in the rate of deterioration of lung function as measured by predicted FEV1, or improvement in CT scan lung density
Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include hypersensitivity reactions, etc.
|INDICATION(S)||DOSAGE & ADMINISTRATION|
|All indications||60 mg/kg by intravenous (IV) infusion administered once every 7 days (weekly)|
LENGTH OF AUTHORIZATION
Coverage will be provided for 12 months and may be renewed.
Refer to DOSAGE LIMITS below
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).
Hernandez P, Balter M, et al. Alpha-1 antitrypsin deficiency targeted testing and augmentation therapy: a Canadian Thoracic Society clinical practice guideline. Can Respir J. 2012;19(2):109-16.
Lexi-Comp Online. AHFS DI. (2018, February). α1-proteinase inhibitor (human). Retrieved May 23, 2019 from Lexi-Comp Online with AHFS.
Mayo Foundation for Medical Education and Research. (2016, June).Mayo Clinic. Test ID: A1ALC. Alpha-1-Antitrypsin Prototype S/Z by LC-MS/MS, Serum. Mayo medical laboratories. Retrieved May 9, 2016 from http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/61767.
MICROMEDEX Healthcare Series. Drugdex Evaluations. (2018, September). Alpha1-proteinase inhibitor human. Retrieved May 23, 2019 from MICROMEDEX Healthcare Series.
Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. 668-682. Accessed January 11, 2018. doi: HTTP://DX.DOI.ORG/10.15326/JCOPDF.3.3.2015.0182
Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chronic Obstr Pulm Dis. 2016; 3(3): 668-682
U. S. Food and Drug Administration. (2007, May). Center for Biologic Research and Evaluation. Aralast® NP(alpha1-proteinase inhibitor [human]). Retrieved May 23, 2019 fromhttps://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM051590.pdf
U. S. Food and Drug Administration. (2010, August). Center for Biologic Research and Evaluation. Glassia® (alpha1-proteinase inhibitor [human], intravenous). Retrieved May 23, 2019 from https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM217890.pdf
U. S. Food and Drug Administration. (2017, September). Center for Biologic Research and Evaluation. Alpha1-proteinase inhibitor (human) Prolastin®-C. Retrieved May 23, 2019 from https://www.fda.gov/downloads/BiologicsBloodVaccines/UCM209676.pdf
U. S. Food and Drug Administration. (2003, July). Center for Biologic Research and Evaluation. Alpha1-proteinase inhibitor (human) Zemaira®. Retrieved May 23, 2019 from https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM172304.pdf
ORIGINAL EFFECTIVE DATE: 12/1/2016
MOST RECENT REVIEW DATE: 9/30/2019
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
This document has been classified as public information.
Maximum billable units per dose and over time by indication as a Medical Benefit Billable Unit = 10 mg