CurrentNeighborhood Health Plan of Rhode IslandPolicy 2100-A

Haegarda (C1 inhibitor) — Routine prophylaxis for hereditary angioedema

Policy governs prior authorization, documentation, and coverage criteria for Haegarda used for routine prophylaxis to prevent hereditary angioedema (HAE) in members aged 6 years and older.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyHaegarda (C1 inhibitor) — Routine prophylaxis for hereditary angioedema

Policy CodePolicy 2100-A

Change TypeNo material change

Effective Date

Next Review Date

Key ActionSubmit C1‑INH antigenic and functional levels (and genetic testing when applicable) with prior authorization; approvals may be granted up to 6 months.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

≥6 yrsminimum age for covered indication

6 monthsauthorization length

≥50%required efficacy for continuation

High‑dose antihistaminestep therapy when applicable

Coverage Criteria for Haegarda (C1‑INH)

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Age: Patient is 6 years of age or older.>=6 years

FDA‑approved age

Indication: Requested for routine prophylaxis to prevent hereditary angioedema (HAE) attacks.

FDA‑approved indication

Diagnostic confirmation

C1-INH deficiency/dysfunction: Member has C1 inhibitor deficiency or dysfunction as confirmed by laboratory testing (C1-INH antigenic level below laboratory lower limit of normal OR normal antigenic level with functional C1-INH <50% or functional level below the laboratory lower limit).antigenic low OR functional <50% or below lab LLN
supported by lab testing
Normal C1-INH with other evidence: Member has normal C1-INH on testing AND (i) genetic testing confirming a pathogenic mutation (F12, ANGPT1, PLG, KNG1, HS3ST6, MYOF) OR (ii) documented family history of angioedema and angioedema refractory to a trial of high‑dose antihistamine therapy (e.g., cetirizine 40 mg/day or equivalent for ≥1 month).genetic mutation OR family history + failed antihistamine trial
genetic confirmation or family history required

Continuation Therapy

Covered when ALL of the following are met

Meets initial criteria: Member continues to meet criteria for initial approval.

See Initial Therapy

Efficacy: Member has experienced a significant reduction in frequency of attacks (e.g., ≥ 50%) since starting treatment.>=50% reduction

example threshold provided in policy

Reduced acute medication use: Member has reduced the use of medications to treat acute attacks since starting treatment.

documented in chart notes

Provider Requirements, Authorization Duration, and Documentation

Prior Authorization

Prior authorization duration — up to 6 months

Prior authorization may be granted for up to 6 months for both initial and continuation approvals when the coverage criteria are met.

Step Therapy

High‑dose antihistamine trial required when applicable

If the member has a normal C1‑INH antigenic level but a family history of angioedema, the member must have a trial of high‑dose antihistamine therapy (e.g., cetirizine 40 mg per day or equivalent) for at least 1 month unless genetic testing documents a pathogenic mutation.

Trial duration: ≥1 month
Example regimen: cetirizine 40 mg/day or equivalent

Documentation Required

Initial authorization documentation — labs and genetic testing

For initial authorization submit documented C1 inhibitor functional and antigenic protein levels and, if applicable, genetic testing for F12, ANGPT1, PLG, KNG1, HS3ST6, or MYOF; include chart notes confirming family history and prior high‑dose antihistamine trial when relevant.

C1 inhibitor functional and antigenic protein levels
Genetic testing: F12, ANGPT1, PLG, KNG1, HS3ST6, MYOF (if applicable)
Chart notes confirming family history and refractory response to high‑dose antihistamine trial (if applicable)

Documentation Required

Continuation documentation — show attack reduction and decreased acute medication use

For continuation of therapy submit chart notes demonstrating a significant reduction in frequency of attacks (e.g., ≥50%) and evidence of reduced use of medications to treat acute attacks since starting treatment.

Documentation of ≥50% reduction in attack frequency (example threshold)
Documentation of decreased use of acute‑attack medications

Note

Prescriber specialty requirement

The medication must be prescribed by or in consultation with a prescriber who specializes in the management of hereditary angioedema.

Denial Risk

Non‑FDA indications considered investigational

Requests for indications other than routine prophylaxis to prevent HAE attacks in patients 6 years of age and older are considered experimental/investigational and not medically necessary and may be denied.

Denial Risk

Insufficient diagnostic confirmation may lead to denial

Lack of laboratory confirmation of C1‑INH deficiency/dysfunction or absence of required genetic testing or documented family history (where applicable) may result in denial of the request.

Required lab evidence: low C1‑INH antigenic level OR normal antigenic with functional C1‑INH <50% (or below lab lower limit)
Required genetic testing when applicable: F12, ANGPT1, PLG, KNG1, HS3ST6, MYOF
If normal C1‑INH, must have genetic confirmation OR documented family history plus failed high‑dose antihistamine trial

Key Definitions

C1‑INH deficiency or dysfunction — diagnostic thresholds and descriptions

Diagnostic definitionC1‑INH deficiency or dysfunction is demonstrated by either: C1 inhibitor antigenic level below the laboratory lower limit of normal, OR a normal antigenic level with C1‑INH functional level <50% or below the laboratory lower limit of normal.

Alternate phrasing used in policyNormal C1‑INH antigenic level and a low C1‑INH functional level (functional C1‑INH less than 50% or below the lab lower limit).

Requirement to exclude other causesOther causes of angioedema must be ruled out (examples: ACE‑inhibitor induced angioedema, estrogen‑related angioedema, allergic angioedema).

Laboratory referenceUse laboratory‑specific lower limits of normal when interpreting antigenic and functional C1‑INH results.

HAE with normal C1‑INH — genetic mutation list and testing guidance

Genetic mutations listedPathogenic mutation in one of: F12, ANGPT1 (angiopoietin‑1), PLG (plasminogen), KNG1 (kininogen‑1), HS3ST6, or MYOF (myoferlin).

Genetic testing guidanceGenetic testing confirming a pathogenic mutation in the listed genes satisfies diagnostic criteria for HAE with normal C1‑INH.

Family history alternativeIf C1‑INH antigenic level is normal, documented family history of angioedema plus angioedema refractory to a high‑dose antihistamine trial (cetirizine 40 mg/day or equivalent for ≥1 month) also satisfies criteria.

High‑dose antihistamine trial specificsHigh‑dose antihistamine = cetirizine 40 mg per day (or equivalent) for at least one month when used to demonstrate refractoriness prior to approval absent a pathogenic mutation.