HIGHMARK COMMERCIAL MEDICAL POLICY - PENNSYLVANIA

 
 

Medical Policy:
I-122-007
Topic:
Treatment of Hereditary Angioedema (HAE)
Section:
Injections
Effective Date:
October 1, 2018
Issued Date:
October 1, 2018
Last Revision Date:
September 2018
Annual Review:
February 2018
 
 

Hereditary angioedema (HAE) is a disorder characterized by recurrent episodes of non-allergic, severe swelling (angioedema) in the absence of urticaria or hives. Patients experience swelling episodes that resolve within 2 to 5 days without treatment; however laryngeal swelling can be fatal. The most common areas of the body to develop swelling are the limbs, face, intestinal tract, and airway. Minor trauma or stress may trigger an attack, but swelling often occurs without a known trigger. Episodes involving the intestinal tract cause severe abdominal pain, nausea, and vomiting. Swelling in the airway can restrict breathing and lead to life-threatening obstruction of the airway.

Bradykinin is a vasodilator that results in the swelling that is associated with angioedema. Since the angioedema is non-allergic, histamines are not involved and antihistamines are not effective. HAE can also occur because of a deficiency or malfunction of the C1 inhibitor in the body which regulates the coagulation pathway. Missing or low levels of the protein C1 esterase inhibitor (C1-INH). Lack of adequate amounts of C1-INH impact vascular permeability, causing fluid leakage in blood vessels and capillaries.

There are three types of hereditary angioedema: type I (low C1-INH levels), accounting for roughly 85% of cases; type II (poorly functioning C1-INH levels), accounting for roughly 15% of cases; and type III (normal functioning C1-INH), considered to be very rare, occurring predominantly in women. The different types have similar signs and symptoms, but are distinguished based on the underlying causes and levels of C1-INH protein. Treatment options consist of on-demand therapy for acute HAE attacks in order to reduce the severity and duration of attacks and ongoing preventive or prophylactic therapy to prevent attacks in individuals who experience frequent or severe attacks, with dramatic lifestyle impairment. Treatment options consist of various mechanisms of action, including C1 esterase inhibitors, plasma kallikrein inhibitors and bradykinin B2 receptor antagonists.

Policy Position Coverage is subject to the specific terms of the member's benefit plan.

Prophylaxis Therapy

Hereditary Angioedema Type I and II

C1 Esterase Inhibitor [Human] (Cinryze®) or lanadelumab-flyo (TAKHZYRO™) may be considered medically necessary when ALL of the following criteria are met:

  • The individual meets the following age requirements:
    • C1 Esterase Inhibitor [Human] (Cinryze): greater than or equal to six (6) years of age; or
    • Lanadelumab-flyo (TAKHZYRO): greater than or equal to twelve (12) years of age; and
  • Administration is for routine prophylaxis against hereditary angioedema (HAE) attacks; and  
  • The individual must have a diagnosis of HAE where diagnosis is based on evidence of a low C4 level (C4 less than 14 mg/dL; normal range 14 to 40 mg/dL, or C4 below the lower limit of normal as defined by the laboratory performing the test) and ONE of the following laboratory tests:*
    • A low C1 inhibitor (C1INH) antigenic level (C1INH less than 19 mg/dL; normal range 19 to 37 mg/dL, or C1INH antigenic level below the lower limit of normal as defined by the laboratory performing the test); or
    • A normal C1INH antigenic level (C1INH normal range to 19 to 37 mg/dL) and a low C1INH functional level (functional C1INH less than 50%); or below the lower limit of normal as defined by the laboratory performing the test); and
  • History of severe attack(s) with swelling of hands, feet, limbs, face, intestinal tract or airway; and
  • Medication is prescribed by either an immunologist, allergist or rheumatologist; and
  • Medications known to cause angioedema (i.e. ACE inhibitors, estrogens, angiotensin II receptor blockers) have been evaluated and discontinued when appropriate.

*Values defined by the laboratory performing the test.

The use of C1 Esterase Inhibitor [Human] (Cinryze) or lanadelumab (TAKHZYRO) for all other indications is considered not medically necessary.

J0598

J3590

 

 

 

 

 




Hereditary Angioedema Type III

C1 Esterase Inhibitor [Human] (Cinryze) may be considered medically necessary when ALL of the following criteria are met:

  • Administration is for routine prophylaxis against HAE attacks in adolescents (greater than or equal to six (6) years of age) and adult patients diagnosed with HAE; and
  • Documented normal* or near normal C4, C1INH antigen, and C1INH function; and ONE of the following:
    • Demonstration of a F12 mutation that is associated with the disease; or
    • A positive family history of angioedema; and
  • History of severe attack(s)  in the absence of concomitant hives with swelling of hands, feet, limbs, face, intestinal tract or airway; and
  • Medication is prescribed by either an immunologist, allergist or rheumatologist; and
  • Medications known to cause angioedema (i.e. ACE inhibitors, estrogens, angiotensin II receptor blockers) have been evaluated and discontinued when appropriate; and
  • Trial and failure of second generation antihistamines (e.g. cetirizine, desloratadine, fexofenadine, levocetirizine, or loratadine).

*Values defined by the laboratory performing the test. The use of C1 Esterase Inhibitor [Human] (Cinryze) for all other indications is considered not medically necessary.

The use of C1 Esterase Inhibitor [Human] (Cinryze) for all other indications is considered not medically necessary.

J0598

 

 

 

 

 

 




Acute Attacks

Hereditary Angioedema Type I and II

Icatibant (Firazyr®), ecallantide (Kalbitor®), C-1 Esterase Inhibitor [Human] (Berinert®) or C1 esterase inhibitor [recombinant] (Ruconest®) may be considered medically necessary for the treatment of acute angioedema attacks when the following criteria are met: 

  • The individual meets the following age requirement:
    • Icatibant (Firazyr): greater than or equal to 18 years of age; or
    • Ecallantide (Kalbitor): greater than or equal to 12 years of age; or
    • C-1 esterase inhibitor [human] (Berinert): greater than or equal to five (5) years of age; or  
    • C1 esterase inhibitor [recombinant] (Ruconest): greater than 13 years of age; and
  • The individual must have a diagnosis of HAE where diagnosis is based on evidence of a low C4 level (C4 less than 14 mg/dL; normal range 14 to 40 mg/dL, or C4 below the lower limit of normal as defined by the laboratory performing the test); and
    • A low C1 inhibitor (C1INH) antigenic level (C1INH less than 19 mg/dL; normal range 19 to 37 mg/dL, or C1INH antigenic level below the lower limit of normal as defined by the laboratory performing the test); or
    • A normal C1INH antigenic level (C1INH normal range to 19 to 37 mg/dL) and a low C1INH functional level (functional C1INH less than 50 %); or
    • Below the lower limit of normal as defined by the laboratory performing the test); and
  • The individual must be experiencing at least one (1) symptom of the moderate or severe attack (e.g., airway swelling, severe abdominal pain, facial swelling, nausea and vomiting, painful facial distortion); and
  • Medication is prescribed by either an immunologist, allergist or rheumatologist; and
  • Medications known to cause angioedema (i.e. ACE inhibitors, estrogens, angiotensin II receptor blockers) have been evaluated and discontinued when appropriate; and
  • Patient not self-administering two acute medications on the same day ; and
  • Not used in combination with other approved treatments for acute HAE attacks (e.g. C-1 Esterase Inhibitor [Human] (Berinert), icatibant (Firazyr), ecallantide (Kalbitor) or C1 esterase inhibitor [recombinant] (Ruconest).

The use of Icatibant (Firazyr), ecallantide (Kalbitor), C-1 Esterase Inhibitor [Human] (Berinert) or C1 esterase inhibitor [recombinant] (Ruconest) for all other indications is considered not medically necessary.

J0596

J0597

J0598

J1290

J1744

 

 




Hereditary Angioedema Type III

Icatibant (Firazyr), Ecallantide (Kalbitor), C-1 Esterase Inhibitor [Human] (Berinert), or C1 esterase inhibitor [recombinant] (Ruconest) may be considered medically necessary in an individual who experiences attacks associated with HAE when the following criteria are met:

  • The individual meets the following age requirements:
    • Icatibant (Firazyr): greater than or equal to 18 years of age; or
    • Ecallantide (Kalbitor): or greater than or equal to12 years of age; or
    • C-1 esterase inhibitor [human] (Berinert): greater than or equal to five (5) years of age; or
    • C1 esterase inhibitor [recombinant] (Ruconest): greater than 13 years of age; and
  • Documented normal or near normal C4, C1INH antigen, and C1INH function; and ONE of the following:
    • Demonstration of a F12 mutation that is associated with the disease; or
    • A positive family history of angioedema; and
  • History of severe attack(s) in the absences of concomitant hives with swelling of hands, feet, limbs, face, intestinal tract or airway; and
  • Medication is prescribed by either an immunologist, allergist or rheumatologist; and
  • Medications known to cause angioedema (i.e. ACE inhibitors, estrogens, angiotensin II receptor blockers) have been evaluated and discontinued when appropriate; and
  • Trial and failure of second generation antihistamines (e.g. cetirizine, desloratadine, fexofenadine, levocetirizine, or loratadine); and
  • Not used in combination with other approved treatments for acute HAE attacks (e.g. C-1 Esterase Inhibitor [Human] (Berinert), icatibant (Firazyr), ecallantide (Kalbitor) or C1 esterase inhibitor [recombinant] (Ruconest).

According to an International Consensus Statement on Hereditary Angioedema testing must be performed more than once to confirm the diagnosis.

The use of icatibant (Firazyr), ecallantide (Kalbitor), C-1 Esterase Inhibitor [Human] (Berinert) or C1 esterase inhibitor [recombinant] (Ruconest®) for all other indications is considered not medically necessary.

J0596

J0597

J0598

J1290

J1744

 

 




Note: Product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines.


Related Policies

Refer to Pharmacy Policy Bulletins J-423 on Firazyr; and J-424 for Berinert and Ruconest.


Covered Diagnosis Codes for J0598, J1290, J0596, J0597, J1744

 

 

D84.1

 

 

 

 

 

 



Place of Service: Outpatient

Treatment of Hereditary Angioedema (HAE) 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.


The policy position applies to all commercial lines of business


Denial Statements

Services that do not meet the criteria of this policy will not be considered medically necessary. A network provider cannot bill the member for the denied service unless: (a) the provider has given advance written notice, informing the member that the service may be deemed not medically necessary; (b) the member is provided with an estimate of the cost; and (c) the member agrees in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.



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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 or other circumstances may warrant individual consideration, based on review of applicable medical records, as well as other regulatory, contractual and/or legal requirements.

Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

Highmark retains the right to review and update its medical policy guidelines at its sole discretion. These guidelines are the proprietary information of Highmark. Any sale, copying or dissemination of the medical policies is prohibited; however, limited copying of medical policies is permitted for individual use.

Discrimination is Against the Law
The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer:

  • Provides free aids and services to people with disabilities to communicate effectively with us, such as:
  • Qualified sign language interpreters
  • Written information in other formats (large print, audio, accessible electronic formats, other formats)

  • Provides free language services to people whose primary language is not English, such as:
  • Qualified interpreters
  • Information written in other languages
  • If you need these services, contact the Civil Rights Coordinator.

    If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

    You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:

    U.S. Department of Health and Human Services
    200 Independence Avenue, SW
    Room 509F, HHH Building
    Washington, D.C. 20201
    1-800-368-1019, 800-537-7697 (TDD)

    Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

    Insurance or benefit/claims administration may be provided by Highmark, Highmark Choice Company, Highmark Coverage Advantage, Highmark Health Insurance Company, First Priority Life Insurance Company, First Priority Health, Highmark Benefits Group, Highmark Select Resources, Highmark Senior Solutions Company or Highmark Senior Health Company, all of which are independent licensees of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield plans.





    Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

    Discrimination is Against the Law
    The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer:

  • Provides free aids and services to people with disabilities to communicate effectively with us, such as:
  • Qualified sign language interpreters
  • Written information in other formats (large print, audio, accessible electronic formats, other formats)

  • Provides free language services to people whose primary language is not English, such as:
  • Qualified interpreters
  • Information written in other languages
  • If you need these services, contact the Civil Rights Coordinator.

    If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295 , TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

    You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:

    U.S. Department of Health and Human Services
    200 Independence Avenue, SW
    Room 509F, HHH Building
    Washington, D.C. 20201
    1-800-368-1019, 800-537-7697 (TDD)

    Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.