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Treatment of Hereditary Angioedema (HAE)

Section: Injections
Effective Date: October 01, 2019
Revised Date: September 30, 2019

Description

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 (missing or low levels of the protein C1 esterase inhibitor [C1-INH]) or malfunction of the C1 inhibitor in the body which regulates the coagulation pathway. 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.

Criteria

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

Federal Employee Program members (FEP) should check with their Retail Pharmacy Program to determine if prior approval is required by calling the Retail Pharmacy Program at 1-800-624-5060 (TTY: 1-800-624-5077). FEP members can also obtain the list through the www.fepblue.org website.

Table 1: Lab Values* Consistent for Diagnosis of HAE 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)

*Values defined by the laboratory performing the test

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)
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)

HAE Type I and II

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

  • One of the following:
    • Administration is for routine prophylaxis against hereditary angioedema (HAE) attacks in individuals greater than or equal to six (6) years of age diagnosed with HAE and will not be used with other medications for the prevention of HAE attacks; or
    • Administration is for the treatment of HAE acute attacks; and
  • The individual must have a diagnosis of HAE where diagnosis is based on evidence of a low C4 level and ONE of the following laboratory tests listed in Table 1; 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; and

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

Procedure Codes

J0598

HAE Type III

C1 esterase inhibitor [human] (Cinryze) may be considered medically necessary when ALL of the following criteria are met:

  • One of the following:
    • Administration is routine prophylaxis against hereditary angioedema (HAE) attack in individuals greater than or equal to six (6) years of age diagnosed with HAE and will not be used with other medications for the prevention of HAE attacks; or
    • Administration is for the the treatment of HAE acute attacks; 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); and

*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.

Procedure Codes

J0598

Acute Attacks

HAE Type I and II

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:
    • 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 and ONE of the following laboratory tests listed in Table 1; 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
  • Individual is not self-administering two acute medications on the same day; and
  • For C-1 esterase inhibitor [human] (Berinert) or C1 esterase inhibitor [recombinant] (Ruconest) ONLY: documentation of individual’s weight; and
  • Not used in combination with other approved treatments for acute HAE attacks.

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

Procedure Codes

J0596J0597J0598J1290

HAE Type III

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:
    • Ecallantide (Kalbitor): or 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
  • 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
  • For C-1 esterase inhibitor [human] (Berinert) or C1 esterase inhibitor [recombinant] (Ruconest) ONLY: documentation of individual’s weight; and
  • Not used in combination with other approved treatments for acute HAE attacks.

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

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

Procedure Codes

J0596J0597J0598J1290

Note: In addition to the above criteria, 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. Blue Cross Blue Shield of North Dakota may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.

Diagnostic Codes

Covered Diagnosis Codes for J0596, J0597, J0598, J1290

D84.1

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