Background
Scope and purpose
Intended audience
Methods
Committee Members, Guideline Authors and Conference Participants
Identifying the evidence
Summarizing and evaluating the evidence
Recommendation development and approval
Recommendation | Level of evidence and strength of recommendation |
---|---|
Diagnosis of HAE | |
1. The diagnosis of HAE-1/2 should be made by measuring plasma levels of C4, C1-INH antigen and, when necessary, C1-INH function | High, Strong |
2. All individuals with a positive family history should be considered to be at risk of HAE and should be screened as early as possible | Consensus, Strong |
Acute treatment of HAE-1 and HAE-2 | |
3. Effective therapy should be used for the acute treatment of attacks of angioedema to reduce duration and severity of attacks | High, Strong |
4. Intravenous pdC1-INH is an effective therapy for the acute treatment of attacks | High, Strong |
5. Icatibant is an effective therapy for the acute treatment of attacks | High, Strong |
6. Ecallantide is an effective therapy for the acute treatment of attacks | High, Strong |
7. Intravenous rhC1-INH is an effective therapy for the acute treatment of attacks | High, Strong |
8. Attenuated androgens should not be used for the acute treatment of attacks | Low, Strong |
9. Tranexamic acid should not be used for the acute treatment of attacks | Low, Strong |
10. Frozen plasma could be used for acute treatment of attacks if other recommended therapies are not available | Low, Strong |
11. Attacks should be treated early to reduce morbidity (level of evidence: moderate) and mortality (level of evidence: consensus) | Moderate, Strong/Consensus, Strong |
12. All attacks of angioedema involving the upper airway are medical emergencies and must be treated immediately | Low, Strong |
Acute treatment and short-term prophylaxis of HAE in pregnant patients | |
13. pdC1-INH is the treatment of choice for angioedema attacks in pregnant HAE-1/2 patients | Consensus, Strong |
Acute treatment of HAE in paediatric patients | |
14. All paediatric patients diagnosed with HAE should have access to acute treatment, including those that are symptom free | Consensus, Strong |
15. Intravenous pdC1-INH is an effective therapy for the acute treatment of HAE-1/2 attacks in paediatric patients | Moderate, Strong |
16. Icatibant is an effective therapy for the acute treatment of HAE-1/2 attacks in paediatric patients | Consensus, Strong |
17. Intravenous rhC1-INH is an effective therapy for the acute treatment of HAE-1/2 attacks in paediatric patients | Consensus, Strong |
18. Ecallantide is an effective therapy for the acute treatment of HAE-1/2 attacks in adolescent patients | Consensus, Strong |
Diagnosis of HAE with normal C1-inhibitor | |
19. If the diagnosis of HAE nC1-INH is suspected, a referral should be made to a physician who has expertise with this condition. Testing for gene variants known to be associated with the condition should be performed | Low, Strong |
Acute treatment of HAE with normal C1-inhibitor | |
20. pdC1-INH is an effective therapy for the acute treatment of attacks in patients with HAE nC1-INH | Moderate, Strong |
21. Icatibant is an effective therapy for the acute treatment of attacks in patients with HAE nC1-INH | Consensus, Strong |
Short-term prophylaxis | |
22. Short-term prophylaxis should be considered prior to known patient-specific triggers and for any medical, surgical or dental procedures | Low, Strong |
23. HAE-specific acute treatment should be available during and after any procedure | Low, Strong |
24. Intravenous pdC1-INH should be used for short-term prophylaxis in patients with HAE | Consensus, Strong |
Long-term prophylaxis in HAE-1 and HAE-2 | |
25. Long-term prophylaxis may be appropriate for some patients to reduce frequency, duration, and severity of attacks | High, Strong |
26. pdC1-INH is an effective therapy for long-term prophylaxis in patients with HAE-1/2 | High, Strong |
27. Lanadelumab is an effective therapy for long-term prophylaxis in patients with HAE-1/2 | High, Strong |
28. Subcutaneous C1-INH or lanadelumab should be used as first-line therapy for long-term prophylaxis in patients with HAE-1/2 | Consensus, Strong |
29. Attenuated androgens and anti-fibrinolytics should not be used as first-line therapy for long-term prophylaxis in patients with HAE-1/2 | Consensus, Strong |
30. Attenuated androgens are an effective therapy for long-term prophylaxis in some patients with HAE-1/2 | Moderate, Strong |
31. All patients should have a management plan including immediate access to effective treatment for attacks, even when on prophylaxis | Consensus, Strong |
Long-term prophylaxis in pregnant HAE patients | |
32. When long-term prophylaxis is indicated in pregnancy, pdC1-INH is the treatment of choice | Consensus, Strong |
33. Attenuated androgens should not be used during pregnancy or during the breastfeeding period | Consensus, Strong |
Long-term prophylaxis in paediatric HAE patients | |
34. When long-term prophylaxis is indicated in paediatric patients, pdC1-INH is the treatment of choice | Consensus, Strong |
35. Androgens should not be used for long-term prophylaxis in paediatric patients | Moderate, Strong |
Self-administration | |
36. All HAE patients should be trained on self-administration of HAE-specific therapies if they are suitable candidates. If patients cannot self-administer therapy, provisions should be made to ensure timely access to all appropriate therapies | Low, Strong |
Approach to individualized therapy | |
37. The decision to start or stop long-term prophylaxis depends on multiple factors and should be made by the patient and an HAE specialist | Consensus, Strong |
Quality of life | |
38. Healthcare providers should routinely assess quality of life in HAE patients using validated instruments in order to optimize HAE management | Consensus, Strong |
Comprehensive care | |
39. Comprehensive care for all patients with HAE should be provided to optimize treatment and outcomes | Consensus, Strong |
40. All HAE patients should be informed about HAE patient association(s) | Consensus, Strong |
Registries | |
41. Physicians should participate in an HAE registry and offer patients enrolment | Consensus, Strong |
Guideline recommendations
Diagnosis of HAE-1/2
Background
Clinical considerations
Clinical considerations
Acute treatment of HAE-1 and HAE-2
Background
HAE-specific treatment | Product name and company | Mechanism of action | Approved indications | Dose and route of administration | County licensed and age indications |
---|---|---|---|---|---|
pdC1-INH | Berinert®a (CSL) | Replaces C1-INH | Acute treatment | 20 U/kg intravenous | Australia, Canada, EU, USA (adult and pediatric) |
Pre-procedural | Adults: 1000 U Pediatrics: 15 to 30 U/kg body weight | EU (adult and pediatric) | |||
Cinryze® (Shire—now part of Takeda) | Replaces C1-INH | Acute treatment | ≥ 12 years: 1000 U intravenous 2–11 years: 1000 U (> 25 kg body weight) 500 U (< 25 kg body weight) | Australia (≥ 12 years) EU (≥ 2 years) | |
Pre-procedural | ≥ 12 years: 1000 U intravenous 2–11 years: 1000 U (> 25 kg body weight) 500 U (< 25 kg body weight) | Australia (≥ 12 years) EU (≥ 2 years) | |||
Long-term prophylaxis | 1000 U intravenous q 3–4 days (6–11 years 500 U q 3–4 days)b | Australia, Canada (≥ 12 years) EU, USA (≥ 6 years) | |||
Haegarda® (CSL) | Replaces C1-INH | Long-term prophylaxis | 60 U/kg body weight twice weekly (every 3–4 days) | Australiac, Canada, EUd, USA (≥ 12 years) | |
rhC1-INH | Ruconest® (Ruconest) | Replaces C1-INH | Acute treatment | 50 U/kg intravenous (< 84 kg); 4200 U intravenous (≥ 84 kg) | EU (adults), USA (adults and adolescents) |
Ecallantide | Kalbitor® (Shire—now part of Takeda) | Selective, reversible inhibitor of plasma kallikrein | Acute treatment | 30 mg (3 × 10 mg/1 ml) subcutaneous injections | USA (≥ 12 years) |
Icatibant | Firazyr® (Shire—now part of Takeda) | Synthetic selective and specific antagonist of bradykinin 2 receptor | Acute treatment | 30 mg subcutaneous injection; dose-adjusted for adolescents < 65 kg and children ≥ 2 yearse | USA (≥ 18 years) Australia, Canada, EU (≥ 2 years) |
Lanadelumab | Takhzyro® (Shire—now part of Takeda) | Fully human monoclonal antibody that binds plasma kallikrein and inhibits its proteolytic activity | Long-term prophylaxis | 300 mg subcutaneous injection every 2 weeks a dosing interval of 300 mg every 4 weeks may be considered if the patient is well-controlled (e.g., attack free) for more than 6 months | Australia, Canada, EU, USA (≥ 12 years) |
Clinical considerations
Clinical considerations
Clinical considerations
Clinical considerations
Clinical considerations
Clinical considerations
Clinical considerations
Clinical considerations
Clinical considerations
Acute treatment and short-term prophylaxis of HAE in pregnant patients
Background
Clinical considerations
Acute treatment of HAE in paediatric patients
Background
Clinical considerations
Clinical considerations
Clinical considerations
Clinical considerations
Clinical considerations
Diagnosis of HAE with normal C1-inhibitor
Background
Clinical considerations
Acute treatment of HAE with normal C1-inhibitor
Background
Clinical considerations
Short-term prophylaxis
Background
Clinical considerations
Long-term prophylaxis in HAE-1 and HAE-2
Background
Clinical considerations
Clinical considerations
Clinical considerations
Clinical considerations
Clinical considerations
Clinical considerations
Long-term prophylaxis in pregnant HAE patients
Background
Clinical considerations
Clinical considerations
Long-term prophylaxis in paediatric HAE patients
Background
Clinical considerations
Clinical considerations
Long-term prophylaxis in HAE with normal C1-inhibitor
Background
Clinical considerations
Self-administration
Background
Clinical considerations
Approach to individualized therapy
Background
Clinical considerations
Quality of life
Background
Clinical considerations
Comprehensive care
Background
Best Clinical Treatment outcomes including a. A comprehensive care team made up of nurse coordinator, clinician, social worker, data manager, pain management specialist, genetic counsellor, and administrative support b. Access to specialized diagnostic testing c. Access to home treatment d. A networked Patient Information System to facilitate product recalls—collect data on therapy outcome measures and safety, and facilitate participation in clinical trials e. Access to clinical advances as they become available f. Access to 24 hour support g. Access to up-to-date standards of care, including standardized wallet cards h. Tracking and intermittent audit of quality outcomes including beneficial and adverse outcomes through secure, comprehensive and networked data management Education of patients and staff regarding a. Responsible Self/Family Care (home care model) with home and self-infusion/administration instruction and support b. Developments in the cause, diagnosis, treatment, outcomes, and prognosis of HAE c. Changes in the administrative management of the clinic An environment conducive to research including a. Access to and support for clinical trials of new treatments b. Access to and support for translational research in diagnosis and prognosis c. Access to and support for psychosocial research such as quality of life studies |