Contact Us
Plans and Services Health and Wellness About Wellmark Member Employer Producer Provider
Home Provider Medical Policies and Authorizations Alphabetical Listing


» Working with Wellmark.com
» News
» BlueCard®
» Claims and Payment
» Medical Policies and Authorizations
» Health Management
» Medical, Dental, and Pharmacy
» Credentialing and Contracting
» Quality and Transparency
» Communications and Resources
» Health Care Reform for Providers
printer friendly Printer-Friendly Page

Hereditary Angioedema Therapies*

» Summary» Procedure Codes
» Description» Selected References
» Prior Approval» Policy History
» Policy
 

Medical Policy: 05.01.23 
Original Effective Date: April 2009 
Reviewed: October 2014 
Revised: October 2014 


Benefit Application
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.


Description: 

The intent of the hereditary angioedema (HAE) therapies drug policy is to ensure appropriate selection of patients for therapy based on product labeling, clinical guidelines and clinical studies.  There are presently five (5) HAE therapies included in this policy: Berinert® (C1 esterase inhibitor), Cinryze® (C1  inhibitor), Firazyr® (icatibant) a selective bradykinin B2 receptor antagonist, Kalbitor® (ecallantide) a selective, reversible kallikrien inhibitor and Ruconest® (conestat alfa) a recombinant C1 esterase inhibitor.  All HAE therapies inhibit either the formation or the activity of bradykinin, whose overproduction in the setting of C1 esterase inhibitor (C1INH) deficiency leads to capillary leakage and fluid accumulation in body tissues resulting in HAE symptoms.  Berinert® and Cinryze® are both plasma-derived concentrates of C1INH whose function is to replace the C1INH that is deficient (in either quantity or function) in HAE; Ruconest® is derived from the milk of transgenic rabbits and exerts it’s effect by increasing the plasma levels of functional C1INH; Firazyr® and Kalbitor® exert their therapeutic effects by modulating bradykinin activity.  HAE therapies are administered by either intravenous (Ruconest®, Berinert® and Cinryze®) or subcutaneous (Firazyr® and Kalbitor®) injection.


Berinert®, Firazyr®, and Kalbitor® are approved by the Food and Drug Administration (FDA) for the for the treatment of acute attacks of HAE in patients who are at least 13 years, 18 years, and 12 years of age, respectively. Ruconest® is also approved for the treatment of acute attacks of HAE in adolescents and adults (13 years and older). Cinryze® is approved for the prophylaxis of angioedema attacks in patients with HAE who are at least 13 years of age.

 

Efficacy of Ruconest® has not been established in HAE patient with laryngeal attacks. Ruconest® should not be used in patients with a known or suspected allergy to rabbits and rabbit-derived products.


Top


Prior Approval: 

 

Prior approval is required  Submit a prior approval/treatment request now.


Top


Policy: 

I. Berinert®, Firazyr®, Ruconest® and Kalbitor® may be considered medically necessary for the treatment of acute attacks of HAE when all of the following criteria are met:

  • The medication is being prescribed by an allergy, immunology or hematology specialist
  • The patient meets the age requirement for medication utilization, as described in the requested product's prescribing information
  • The patient has a confirmed diagnosis of HAE based on evidence of a C4 level below the lower limit of normal as defined by the laboratory performing the test with either of the following indicators:
    • C1 esterase inhibitor (C1INH) antigenic level below the lower limit of normal as defined by the laboratory performing the test
    • C1INH functional level below the lower limit of normal as defined by the laboratory performing the test

 Approval will be for 12 months.

 

II. Cinryze®  may be considered medically necessary for routine prophylaxis against acute attacks of HAE when all of the following criteria are met:

  • The medication is being prescribed by an allergy, immunology or hematology specialist
  • The patient is 13 years of age or older
  • The patient has a confirmed diagnosis of HAE based on evidence of a C4 level below the lower limit of normal as defined by the laboratory performing the test with either of the following indicators:
    • C1 esterase inhibitor (C1INH) antigenic level below the lower limit of normal as defined by the laboratory performing the test
    • C1INH functional level below the lower limit of normal as defined by the laboratory performing the test
  • The patient has a documented history of experiencing one of the following:
    • At least one severe HAE attack per month
    • At least one laryngeal attack
    • Disabling symptoms for at least 5 days per month
  • The patient has been treated with the attenuated androgen danazol and experienced inadequate response/intolerance to therapy or danazol therapy is contraindicated (ex: pregnancy or breast feeding).

Initial approval will be for 6 months.  Continued treatment with Cinryze® for subsequent 12 month periods is considered medically necessary for patients who have had a documented therapeutic response to Cinryze® therapy.

 

III. Cinryze®  may be considered medically necessary for surgical prophylaxis against acute attacks of HAE when all of the following criteria are met:

  • The medication is being prescribed by an allergy, immunology or hematology specialist
  • The patient is 13 years of age or older
  • The patient has a confirmed diagnosis of HAE based on evidence of a C4 level below the lower limit of normal as defined by the laboratory performing the test with either of the following indicators:
    • C1 esterase inhibitor (C1INH) antigenic level below the lower limit of normal as defined by the laboratory performing the test
    • C1INH functional level below the lower limit of normal as defined by the laboratory performing the test
  • The patient is scheduled to undergo a surgical procedure or major dental work

Approval will be for 1 month.

 

IV. Berinert®, Cinryze®, Firazyr®, Ruconest® and Kalbitor® are considered not medically necessary for patients who do not meet the criteria set forth above.

 

Quantity limits applyWellmark's quantity limit program.

 

 

CLINICAL RATIONALE

 

HAE is a rare autosomal dominant disease characterized by episodic unpredictable swelling. There are two types of HAE associated with an insufficient amount of circulating levels of C1INH.  Type I HAE is characterized by deficient levels of C1INH  and accounts for approximately 85% of reported cases and Type II HAE is characterized by normal protein levels but with diminished C1INH functional activity that constitutes about 15% of cases. Type III HAE is a newly described variation with normal measurments of C1INH, but attacks are similar to Type 1 and II. The prevelance of Type III HAE is unknown at this time.

 

As HAE is a complex disease, it is highly recommended that patient’s be followed by a physician that is knowledgable about the condition and experienced or familiar with management of treatment options.

 

Therapy for HAE consists of routine (long-term) prophylaxis for patients with frequent or severe attacks, surgical (short-term) prophylaxis for administration when a patient is scheduled to undergo a surgical procedure or major dental work, and rescue treatment for acute attacks.

 

There are currently three types of medications that are used for the prophylaxis of HAE attacks: attenuated androgens, antifibrinolytics, and plasma-derived C1INH concentrates.  Attenuated androgens, of which the most commonly used is danazol, have been shown to be very effective for HAE prophylaxis and are a reasonable first line choice, given their widespread availability and low cost relative to C1INH.  When danazol was studied versus placebo for prevention of attacks, the danazol treatment group reported  2.2% incidence of attacks (1 in 46) versus the placebo treatment group that reported 93.6% (44 of 47) incidence of attacks.  Its presumed mechanism of action is hepatic production of C1INH.  While widely used, antifibrinolytics (e.g. tranexamic acid, aminocaproic acid) are generally not recommended for long-term prophylaxis because data supporting their efficacy are lacking.  However, because they are typically well-tolerated, they are often utilized in patients for whom attenuated androgen therapy is contraindicated.  C1INH concentrates, of which the only agent approved for long-term prophylaxis is Cinryze®, is the newest class of medications indicated for HAE prevention.  While the efficacy of Cinryze® in preventing HAE attacks is well-documented in clinical studies, its cost is extremely high compared to the aforementioned treatment options.  Because of this, it is not unreasonable to reserve Cinryze® therapy for those patients who have had an inadequate response to, or have a documented contraindication or intolerance to, prophylactic therapy with an attenuated androgen.

 

There are four FDA-approved medications for the treatment of acute HAE attacks: Berinert®, Firazyr®  Ruconest®, and Kalbitor®. Limited evidence suggests that patients that use self-administered treatments with these agents result in better efficacy vs. hospital treatment since treatment is started earlier.  However, due to the fact that no comparative studies involving any of the aforementioned medications have been performed, it is yet unclear if any one agent is superior to the others for the treatment of acute HAE attacks.





Top


Procedure Codes and Billing Guidelines: 

  • To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
  • J0597 Injection, C-1 esterase inhibitor (human), Berinert, 10 units
  • J0598 Injection, C1 esterase inhibitor (human), 10 units
  • J1290 Injection, ecallantide, 1 mg
  • J1744 Injection, icatibant, 1 mg
  • J3490 Unclassified drugs
  • J3590 Unclassified biologics
  • C9445 Injection, C-1 esterase Inhibitor (recombinant), Ruconest, 10 units

Top


Selected References: 

  • "Berinert." [prescribing information]. Kankakee, IL: CSL Behring LLC, July 2012.
  • Bowen, T, et al. "2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema." Allergy, Asthma & Clinical Immunology, 6, no. 1 (2010): 24.
  • Cicardi, M, et al. "Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group." Allergy 67 (2012): 147-157.
  • "Cinryze." [prescribing information]. Exton, PA: ViroPharma Biologics, Inc., March 2013.
  • Craig, T, et al. "WAO Guideline for the Management of Hereditary Angioedema." WAO Journal 5, no. 12 (2012): 182-199.
  • "Firazyr." [prescribing information]. Lexington, MA: Shire Orphan Therapies, Inc., August 2011.
  • "Kalbitor." [prescribing information]. Burlington, MA: Dyax Corp., March 2014.
  • Longhurst, H, and M Cicardi. "Hereditary angio-oedema." Lancet 379 (2012): 474-481.
  • Zuraw, B L. "Clinical Practice. Hereditary Angioedema." New England Journal of Medicine 359, no. 10 (2008): 1027-1036.
  • "Berinert." [prescribing information]. Kankakee, IL: CSL Behring LLC, July 2012.
  • Bowen, T, et al. "2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema." Allergy, Asthma & Clinical Immunology, 6, no. 1 (2010): 24.
  • Cicardi, M, et al. "Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group." Allergy 67 (2012): 147-157.
  • "Cinryze." [prescribing information]. Exton, PA: ViroPharma Biologics, Inc., March 2013.
  • Craig, T, et al. "WAO Guideline for the Management of Hereditary Angioedema." WAO Journal 5, no. 12 (2012): 182-199.
  • "Firazyr." [prescribing information]. Lexington, MA: Shire Orphan Therapies, Inc., August 2011.
  • "Kalbitor." [prescribing information]. BurlingtonCambridge, MA: Dyax Corp., March 2014 December 2009.
  • Longhurst, H, and M Cicardi. "Hereditary angio-oedema." Lancet 379 (2012): 474-481.
  • Zuraw, B L. "Clinical Practice. Hereditary Angioedema." New England Journal of Medicine 359, no. 10 (2008): 1027-1036.
  • Frank, M and M Kalinor, "Hereditary Angioedma."  Medscape. http://emedicine.medscape.com/article/135604-overview. Accessed July 1, 2014.
  • Zuraw, B L. “ US Hereditary Angioedema Association Medical Advisory Board 2013  Recommendations for the Management of Hereditary Angioedema Due to C1 Inhibitor Deficiency
  • Danazol. Facts & Comparisons® eAnswers. http://online.factsandcomparisons.com. Accessed July 2, 2014
  • Jelfand GA, et al. “Treatment of hereditary angioedema with danazol. Reversal of clinical and biochemical abnormalities. N Eng J Med, 1976 Dec 23;295(26):1444-8.  http://www.ncbi.nlm.nih.gov/pubmed/792688. Accessed July 2, 2014
  • Ruconest.”[prescribing information]. Raleigh, NC: Salix Pharmaceuticals, Inc. July 2014

Top


Policy History: 

 

 

Date                                        Reason                               Action

August 2011                           Annual review                     Policy renewed

August 2012                           Annual review                     Policy revised

July 2013                               Annual review                     Policy revised

July 2014                               Annual review                     Policy revised

October 2014                         Policy review                      Policy revised

 


Top


Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

*Current Procedural Terminology © 2012 American Medical Association. All Rights Reserved.

 
Contact Information
New information or technology that would be relevant for Wellmark to consider when this policy is next reviewed may be submitted to:
  Wellmark Blue Cross and Blue Shield
  Medical Policy Analyst
  P.O. Box 9232
  Des Moines, IA 50306-9232
FacebookTwitterInstagrampinterestLinked InYou Tube