Treatment of Hereditary Angioedema

Restricted Product(s)

• C1 esterase inhibitor (Berinert® ) intravenous injection for administration by a healthcare professional 
• C1 esterase inhibitor (Cinryze® ) intravenous injection for administration by a healthcare professional 
• C1 esterase inhibitor (Ruconest® ) intravenous injection for administration by a healthcare professional 
• ecallantide (Kalbitor® ) subcutaneous injection for administration by a healthcare professional 
• icatibant (Firazyr® ) subcutaneous injection for administration by a healthcare professional

FDA Approved Use

• C1 Esterase Inhibitor (Berinert® )
  • For treatment of acute abdominal, facial, or laryngeal hereditary angioedema (HAE) attacks in adult and pediatric patients
  • Limitations of use: Not for prophylactic treatment 
• C1 Esterase Inhibitor (Cinryze® )
  • For routine prophylaxis against hereditary angioedema (HAE) attacks in adult, adolescent, and pediatric patients 6 years or older 
• C1 Esterase Inhibitor (Ruconest® )
  • For treatment of acute attacks of hereditary angioedema (HAE) in adult and adolescent patients 
  • Limitations of use: Effectiveness not established in HAE patients with laryngeal attacks 
• Ecallantide (Kalbitor® )
  • For treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years or older 
• Icatibant (Firazyr® )
  • For treatment of acute attacks of hereditary angioedema (HAE) in adult patients 18 years or older

Criteria for Medical Necessity

The restricted product(s) may be considered medically necessary when the following criteria are met:

Initial Criteria for Approval

1. The patient has a diagnosis of hereditary angioedema (HAE) as confirmed through complement testing [medical record documentation required to demonstrate C4 level, C1-inhibitor (C1-INH) level, and C1-INH function where applicable]; AND
   1. If HAE-I, documentation demonstrates low C4 and C1-INH; OR
   2. If HAE-II, documentation demonstrates low C4 with normal C1-INH and decreased C1-INH function; OR
   3. If HAE-III, documentation demonstrates normal C4 and C1-INH AND family history of angioedema; AND 
2. The requested medication is Cinryze; AND
   1. The patient is 6 years of age or older; AND
   2. The requested medication will be used for routine prophylaxis and NOT for treatment of acute HAE attacks [medical record documentation required]; AND 
   3. The patient will NOT be treated with more than one anti-HAE medication used for the prevention of HAE attacks [medical record documentation required]; AND 
   4. The patient has a history of moderate to severe HAE attacks (e.g., airway swelling, severe abdominal pain, facial swelling, nausea and vomiting, painful facial distortion, extremity swelling causing disability) (e.g., 2 or more attacks within the last 2 months) [medical record documentation required]; OR
3. The requested medication is Berinert; AND
   1. The patient is 5 years of age or older; AND
   2. The requested medication will be used to treat acute abdominal, laryngeal, or facial HAE attacks and NOT for prophylaxis of attacks [medical record documentation required]; AND
   3. The patient will NOT be treated with more than one anti-HAE medication used for the acute treatment of HAE attacks [medical record documentation required]; AND
   4. The patient is experiencing at least one symptom of a moderate or severe HAE attack (e.g., airway swelling, severe abdominal pain, facial swelling, nausea and vomiting, painful facial distortion, extremity swelling causing disability) [medical record documentation required]; OR 
4. The requested medication is Ruconest; AND
   1. The patient is 13 years of age or older; AND
   2. The requested medication will be used to treat acute HAE attacks and NOT for prophylaxis of attacks [medical record documentation required]; AND
   3. The patient will NOT be treated with more than one anti-HAE medication used for the acute treatment of HAE attacks [medical record documentation required]; AND
   4. The requested medication will NOT be used to treat laryngeal HAE attacks [medical record documentation required]; AND
   5. The patient is experiencing at least one symptom of a moderate or severe HAE attack (e.g., airway swelling, severe abdominal pain, facial swelling, nausea and vomiting, painful facial distortion, extremity swelling causing disability) [medical record documentation required]; OR 
5. The requested medication is Kalbitor; AND
   1. The patient is 12 years of age or older; AND
   2. The requested medication will be used to treat acute HAE attacks and NOT for prophylaxis of attacks [medical record documentation required]; AND
   3. The patient will NOT be treated with more than one anti-HAE medication used for the acute treatment of HAE attacks [medical record documentation required]; AND
   4. The patient is experiencing at least one symptom of a moderate or severe HAE attack (e.g., airway swelling, severe abdominal pain, facial swelling, nausea and vomiting, painful facial distortion, extremity swelling causing disability) [medical record documentation required]; OR
6. The requested medication is Firazyr; AND
   1. The patient is 18 years of age or older; AND
   2. The requested medication will be used to treat acute HAE attacks and NOT for prophylaxis of attacks [medical record documentation required]; AND
   3. The patient will NOT be treated with more than one anti-HAE medication used for the acute treatment of HAE attacks [medical record documentation required]; AND
   4. The patient is experiencing at least one symptom of a moderate or severe HAE attack (e.g., airway swelling, severe abdominal pain, facial swelling, nausea and vomiting, painful facial distortion, extremity swelling causing disability) [medical record documentation required]; AND
7. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
8. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*
   
   Duration of Approval: 365 days (1 year)

Continuation Criteria for Approval

1. The patient was approved through Blue Cross NC initial criteria for approval; OR
2. The patient would have met initial criteria for approval at the time they started therapy; AND
3. If requested medication is Cinryze:
   1. The requested medication will be used for routine prophylaxis of HAE attacks; AND
   2. The patient will NOT be treated with more than one anti-HAE medication used for the prevention of HAE attacks [medical record documentation required]; AND
   3. The patient has shown a reduction in HAE attacks since initiation of the requested agent; OR 
4. If the requested medication is for acute treatment of HAE attacks (i.e., Berinert, Ruconest, Kalbitor, Firazyr):
   1. The requested medication will be used to treat acute HAE attacks; AND
   2. The patient will NOT be treated with more than one anti-HAE medication used for the acute treatment of HAE attacks [medical record documentation required]; AND
   3. The patient has shown quick symptomatic relief with the requested medication (i.e., decrease in median time to near-complete symptom relief with the patient’s HAE attacks) [medical record documentation required]; AND
5. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
6. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*
   
   Duration of Approval: 365 days (1 year)

*Site of Care Medical Necessity Criteria

1. For requests for injection or infusion administration in an inpatient setting, the injection or infusion may be given if the above medical necessity criteria are met AND the inpatient admission is NOT for the sole purpose of administering the injection or infusion; OR
2. For requests for injection or infusion administration in an outpatient hospital setting, the injection or infusion may be given if the above medical necessity criteria are met AND ONE of the following must be met:
   1. History of mild adverse events that have not been successfully managed through mild pre-medication (e.g., diphenhydramine, acetaminophen, steroids, fluids, etc.); OR
   2. Inability to physically and cognitively adhere to the treatment schedule and regimen complexity; OR
   3. New to therapy, defined as initial injection or infusion OR less than 3 months since initial injection or infusion; OR
   4. Re-initiation of therapy, defined as ONE of the following:
      1. First injection or infusion after 6 months of no injections or infusions for drugs with an approved dosing interval less than 6 months duration; OR
      2. First injection or infusion after at least a 1-month gap in therapy outside of the approved dosing interval for drugs requiring every 6 months dosing duration; OR
   5. Requirement of a change in the requested restricted product formulation; AND
3. If the Site of Care Medical Necessity Criteria in #1 or #2 above are not met, the injection or infusion will be administered in a home-based infusion or physician office setting with or without supervision by a certified healthcare professional.

References

All information referenced is from FDA package insert unless otherwise noted below.

1. Zuraw BL, Banerji A, Bernstein JA, et al. US Hereditary Angioedema Association Medical Advisory Board 2013 recommendations for the management of hereditary angioedema due to C1 inhibitor deficiency. J Allergy Clin Immunol Pract. 2013;1:458.

Policy Implementation/Update Information

April 2022: Criteria change: Removed requirement of two laboratory levels drawn at separate times for HAE-I diagnostic criteria. For prophylactic use (Cinryze), added additional clarification of 2 or more attacks within the last 2 months for history of moderate to severe HAE attacks. Changed age requirement for Berinert to 5 years of age or older. Policy notification given 2/3/2022 for effective date 4/4/2022.
August 2021: Criteria update: Added requirement of no treatment with more than one anti-HAE medication used for the same acute or preventative treatment of HAE attacks as the requested product, for clarity with no change to policy intent.
June 2021: Criteria change: Changed diagnostic requirements; added no use for treatment of laryngeal HAE attacks for Ruconest; added no use with another anti-HAE medication used for prevention or treatment of HAE attacks; continuation criteria added; added maximum units; medical policy formatting change. Policy notification given 4/16/2021 for effective date 6/16/2021.
*Further historical criteria changes and updates available upon request from Medical Policy and/or Corporate Pharmacy.