BlueCross and BlueShield of Montana Medical Policy/Codes
CINRYZE [C1 Esterase Inhibitor (Human)] for Routine Prophylaxis of Hereditary Angioedema (HAE)
Chapter: Drugs - Medical Benefit
Current Effective Date: November 26, 2013
Original Effective Date: November 26, 2013
Publish Date: August 26, 2013
Description

On October 10, 2008 the U.S. Food and Drug Administration (FDA) licensed CINRYZE® for marketing as the first product in the United States intended to protect people with hereditary angioedema (HAE), a rare and potentially life-threatening genetic disease.  HAE affects about 6,000 to 10,000 individuals in the United States.  CINRYZE® is licensed for the prevention of HAE attacks, which can occur spontaneously or during stress, surgery, or infection in patients diagnosed with the disease.  Attacks can produce rapid swelling of the hands, feet, limbs, face, intestinal tract or airway.  Swelling of the larynx can lead to asphyxiation.

HAE is the result of a defect in the gene controlling the synthesis of C1 inhibitor.  C1 inhibitor maintains the natural regulation of the contact, complement, and fibrinolytic systems, that when left unrestricted, can initiate or perpetuate an attack by consuming the already low levels of endogenous C1 inhibitor in HAE patients.  C1 inhibitors have been used in Europe for over ten years for the prophylaxis and acute treatment of HAE.  

CINRYZE® is administered intravenously and can be given every three or four days for routine prevention of HAE attacks.  It is manufactured by Lev Pharmaceuticals Inc., New York, N.Y., through a contract manufacturing agreement with Sanquin Blood Supply Foundation in The Netherlands.

Policy

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions.  Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply.  If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Medically Necessary

Blue Cross and Blue Shield of Montana (BCBSMT) may consider CINRYZE® medically necessary for routine prophylaxis against angioedema attacks in adolescent (nine years of age and older) and adult patients diagnosed with hereditary angioedema (HAE) when the diagnosis has been confirmed by C4 and C1 Inhibitor laboratory testing. 

Investigational

BCBSMT considers CINRYZE® experimental, investigational and unproven for all other treatments including but not limited to treatment of an acute HAE attack.

NOTE:  Safety and efficacy of CINRYZE have not been established in neonates, infants, or children under the age of nine years old and CINRYZE is contraindicated for patients who have manifested life-threatening immediate hypersensitivity reactions, including anaphylaxis to the product.

NOTE: Serum C4 level is a screening test for C1 INH deficiency, as serum C4 is invariably low in untreated HAE (C4 < 30% of mean normal level).  If C4 is normal it is not usually necessary to proceed to C1 INH analysis.  If the C4 level is low then C1 INH level and function may be assessed.

NOTE:  This MP does not address drugs for the treatment of “acute” HAE attacks.

Rationale

Prophylaxis against HAE Attacks

In clinical trials, CINRYZE was effective in preventing or decreasing the frequency of attacks in most but not all HAE patients.  Adverse reactions reported in the study were considered mild or moderate in severity.

The safety and efficacy of CINRYZE prophylaxis therapy to reduce the incidence, severity, and duration of HAE attacks was demonstrated in a single randomized, double blind, placebo controlled multi-center cross-over study of 24 patients.  Patients were screened to confirm a diagnosis of HAE and a history of at least two HAE attacks per month.  Twenty-four patients were randomized to one of two treatment groups: either CINRYZE prophylaxis for 12 weeks followed by 12 weeks of placebo prophylaxis; or randomized to placebo prophylaxis for 12 weeks followed by 12 weeks of CINRYZE prophylaxis.  Two subjects dropped out (one in each arm); 22 patients crossed over into period two and were included in the efficacy analysis.  Patients were given blinded injections (CINRYZE or placebo) every 3 to 4 days, approximately two times per week.  Patients recorded all angioedema symptoms daily.  An attack was defined as the subject-reported indication of swelling at any location following a report of no swelling on the previous day.  The efficacy determination was based on the number of attacks during the 12 week period while receiving CINRYZE as compared to the number of attacks during the placebo treatment period.  The effectiveness of C1 inhibitor prophylaxis in reducing the number of HAE attacks was variable among the subjects.  Patients treated with CINRYZE had a 66% reduction in days of swelling, and decreased in the average severity and duration of attacks.

Treatment for HAE Attacks

Clinical trials are currently being conducted in the United States to determine the efficacy of CINRYZE® for the treatment of acute attacks of HAE. 

2011 Update

A search of peer reviewed literature through April 2011 identified no new clinical trial publications or any additional information that would change the coverage position of this medical policy.

Coding

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

ICD-9 Codes
277.6
Procedural Codes: J0598
References
  1. Micromedex® Healthcare Series: Thomson Micromedex, Greenwood Village, Colorado. 2008.
  2. Sloane DE, Lee CW, Sheffer AL. Hereditary angioedema: Safety of long-term stanozolol therapy. J Allergy Clin Immunol September-2007; 120(3):654-8.
  3. Frank MM, Jiang H. New therapies for hereditary angioedema: Disease outlook changes dramatically. J Allergy Clin Immunol January 2008; 121(1):272-80.
  4. Bernstein, J.A., Hereditary angioedema: a current state-of-the-art review, VIII: current status of emerging therapies.  Ann Allergy Asthma Immunol (2008 Jan) 100(1 Suppl 2):S41-6.
  5. Temino VM, Peebles RS. The spectrum and treatment of Angioedema. Am J Med April 2008; 121(4):282-6.
  6. Weiler C. R., Van Dellen R. G. Diagnostic algorithm for patients with angioedema and possible C1-inhibitor (C1-INH) deficiency as suggested by Bowen et al.27 Mayo Clin Proc. 2006;81:958-72
  7. Cinryze (C1 inhibitor [human]) Prescribing Information. Lev Pharmaceuticals; New York, NY: October 2008.
  8. DrugPoint®Evaluations—C1 Esterase Inhibitor.  Thomson Reuters (Healthcare) Inc., Microdex®1.0 (Healthcare Series).  Available at http://www.thomsonhc.com  (accessed - 2011 May 10).
  9. Cinryze (C1 Esterase Inhibitor [Human]) [package insert]. Exton, PA: ViroPharma Inc., (Accessed April 2011).
History
August 2013  New 2013 BCBSMT medical policy.  CINRYZE® may be considered medically necessary for routine prophylaxis against angioedema attacks in adolescent (nineyears of age and older) and adult patients diagnosed with hereditary angioedema (HAE) when the diagnosis has been confirmed by C4 and C1 Inhibitor laboratory testing.  CINRYZE® is considered experimental, investigational and unproven for all other treatments including but not limited to treatment of an acute HAE attack.
BCBSMT Home
®Registered marks of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield Plans. ®LIVE SMART. LIVE HEALTHY. is a registered mark of BCBSMT, an independent licensee of the Blue Cross and Blue Shield Association, serving the residents and businesses of Montana.
CPT codes, descriptions and material only are copyrighted by the American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS Restrictions Apply to Government Use. CPT only © American Medical Association.
CINRYZE [C1 Esterase Inhibitor (Human)] for Routine Prophylaxis of Hereditary Angioedema (HAE)