C1 Esterase Inhibitor
DESCRIPTION
C1 esterase inhibitor (C1-INH) is a normal constituent of human blood and is a serine proteinase inhibitor or serpin. C1-INH’s primary function is to regulate the activation of the complement and intrinsic coagulation pathway. It also has a role in regulation of the fibrinolytic system. Commercially, C1-INH is derived from purified human plasma which has undergone multiple viral reduction steps.
Individuals with an inherited deficiency of C1-INH suffer from sudden, recurrent edematous swellings of the subcutaneous or submucosal tissues. This condition is known as hereditary angioedema (HAE).
An example of a preparation of C1-INH to prevent HAE attacks is Cinryze®.
An example of a preparation of C1-INH to treat abdominal or facial attacks of HAE is Berinert®.
REFER TO DECISION SUPPORT TREE
POLICY
C1 esterase inhibitor (C1-INH) for the prevention of angioedema attacks is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
C1 esterase inhibitor (C1-INH) for the treatment of angioedema attacks is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
C1-INH for the treatment of other conditions/diseases is considered investigational.
MEDICAL APPROPRIATENESS
C1 esterase inhibitor (C1-INH) for the prevention of angioedema attacks is considered medically appropriate if ALL of the following criteria are met:
The individual has a diagnosis of hereditary angioedema (HAE). (Note: Hereditary angioedema requires laboratory testing to confirm the diagnosis: C4 levels are decreased in virtually all individuals during an attack. Functional C1-INH levels are generally decreased in those with this diagnosis.)
The agent requested is Cinryze®
C1 esterase inhibitor (C1-INH) for the treatment of angioedema attacks is considered medically appropriate if ALL of the following criteria are met:
The individual has a diagnosis of hereditary angioedema (HAE). (Note: Hereditary angioedema requires laboratory testing to confirm the diagnosis: C4 levels are decreased in virtually all individuals during an attack. Functional C1-INH levels are generally decreased in those with this diagnosis.)
Attacks are acute
Location of the attacks is ANY ONE of the following:
Abdomen
Face
The agent requested is Berinert®
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
Tennessee State law requires coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is relative to life-threatening illnesses, such as cancer, AIDS, and coronary heart disease and recognized in one of the standard reference compendia (As defined in the statute: The United States Pharmacopoeia Drug Information, The American Medical Association Drug Evaluations, & The American Hospital Formulary Service Drug Information) or in the medical literature. This law is applicable to all fully insured members. The law is not applicable to self-funded accounts, but coverage for off-label uses may be provided based on the contractual agreement.
IMPORTANT REMINDER
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.
ADDITIONAL INFORMATION
For appropriate dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., The American Hospital Formulary Service Drug Information).
Hereditary angioedema (HAE) occurs in two main types: type I, accounting for 85% of cases, with C1 inhibitor (C1-INH) mutations throughout the gene and type II with mutations on or near exon 8 (15% of cases). HAE requires laboratory testing to confirm the diagnosis. C4 level testing during an HAE attack is a cost effective screen for the condition as an individual’s C4 level is decreased in virtually all true HAE attacks. The diagnosis of HAE is confirmed for most patients by testing for decreased levels of antigenic C1-INH and functional C1-INH, although levels of antigenic C1-INH are normal in individuals with type II HAE.
No controlled studies were found in the published literature that validate the use of either preparation of C1 esterase inhibitor for the prophylaxis, treatment or prevention of any other condition/disease.
SOURCES
Lexi-Comp Online. (2011, May). AHFS DI. C1 Esterase Inhibitor. Retrieved June 15, 2011 from Lexi-Comp Online with AHFS.
MICROMEDEX Healthcare Series. Drugdex Evaluations. (2010, October). C1 Esterase Inhibitor. Retrieved April 22, 2011 from MICROMEDEX Healthcare Series.
U. S. Food and Drug Administration. (2009, October). Center for Biologics Evaluation and Research. Berinert® C1 Esterase Inhibitor (Human) label. Retrieved June 21 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM186268.pdf.
U. S. Food and Drug Administration. (2010, November). Center for Biologics Evaluation and Research. Cinryze® C1 Esterase Inhibitor (Human) label. Retrieved January 6. 2009 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM129918.pdf.
Zuraw, B. L. (2008). Hereditary Angioedema. The New England Journal of Medicine, 359 (10), 1027-1036.
ORIGINAL EFFECTIVE DATE: 6/13/2009
MOST RECENT REVIEW DATE: 8/2/2011
ID_BT
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.
Pharmaceutical Decision Support Tree
C1 Esterase Inhibitor (Cinryze®, Berinert®)
Does the individual have angioedema attacks marked by a decreased C4 level?
If yes, go to question #2
If no, this does not meet medical necessity and/or medical appropriateness criteria
Does the individual have a diagnosis of hereditary angioedema (HAE) confirmed by decreased functional C1 inhibitor (C1-INH) level?
If yes, go to question #3
If no, this does not meet medical necessity and/or medical appropriateness criteria
Is Cinryze® the agent requested for routine prophylaxis against HAE attacks with a dosage of 1000 units intravenous every 3 or 4 days as stated in the FDA approved labeling?
If yes, this meets medical necessity and/or medical appropriateness criteria
If no, go to question #4
Is Berinert® the agent requested for the treatment of angioedema attacks with ALL the following?
Attacks are acute
Location of the attacks is abdominal or facial
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
This document has been classified as public information.