Condition
Hereditary Angioedema
Hereditary angioedema is a rare inherited condition in which too little working C1 inhibitor protein lets bradykinin build up, causing sudden swelling in the skin, gut, or airway. The evidence is strongest for two prescription medicines: icatibant cut symptoms by half in about 2 hours versus nearly 20 on placebo, and ecallantide improved symptoms more than placebo at 4 hours. Those trials measured relief during attacks, not supplements.
Sources: PMID 31290163
- Updated
- How we grade
- 40 studies cited
- Supplements studied
- 0
- Medicines and peptides
- 2
- Graded outcomes
- 9
No supplement studies yetWe haven’t found supplement studies for Hereditary Angioedema. The medicines and peptides studied for it are listed below.
Prescription medicines and peptides studied, for context
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Anaphylaxis Risk SAFETY CONCERN: Anaphylaxis in 3.9% of patients (10/255) in clinical trials. Most within first hour after injection. Black box warning. Must be administered by healthcare professional. Have anaphylaxis treatment available. Self-administration not recommended. | Worsens (the measure goes up) | Small effect | 203 studies | |||
Studies that measured anaphylaxis risk
| ||||||
| Symptom Improvement at 4 Hours EDEMA3 & EDEMA4 Phase 3 (n=168): Treatment outcome score at 4h significantly greater with ecallantide vs placebo (53.4 vs 8.1, P=0.003 in EDEMA4). Mean symptom complex severity score change -0.8 vs -0.4 placebo (P=0.01). Led to FDA approval. | Improves (the measure goes up) | Large effect | 202 studies | |||
Studies that measured symptom improvement at 4 hours
| ||||||
| Time to Symptom Relief EDEMA3+4 pooled analysis: Benefit apparent within 2 hours of dosing. Maintained through 24 hours. Need for rescue intervention: 14% ecallantide vs 36% placebo within 24h. Earlier treatment associated with better outcomes. | Changes; see studies | Moderate effect | 202 studies | |||
Studies that measured time to symptom relief
| ||||||
| Laryngeal Attack Efficacy Subset analysis of laryngeal attacks: Significant improvement in treatment outcome scores. Potential life-saving for airway-threatening attacks. Limited patient numbers in trials - use with close monitoring for severe attacks. | Improves (the measure goes up) | Moderate effect | 203 studies | |||
Studies that measured laryngeal attack efficacy
| ||||||
Key findings
- Anaphylaxis RiskWorsens (the measure goes up)
- Symptom Improvement at 4 HoursImproves (the measure goes up)
- Time to Symptom ReliefChanges; see studies
Safety notes in the studies
- Black box warning.
Studies cited
40 studies from PubMed
- Safety, efficacy, and pharmacokinetics of icatibant treatment in Japanese pediatric patients with hereditary angioedema: A phase 3, open-label study.
- Three-Day Icatibant on Top of Standard Care in Patients With Coronavirus Disease 2019 Pneumonia: A Randomized, Open-Label, Phase 2, Proof-of-Concept Trial.
- Is Icatibant Safe for the Treatment of Hereditary Angioedema During Pregnancy?
- A multicenter, open-label, randomized, proof-of-concept phase II clinical trial to assess the efficacy and safety of icatibant in patients infected with SARS-CoV-2 (COVID-19) and admitted to hospital units without invasive mechanical ventilation: study protocol (ICAT-COVID).
- Short review of SEC, a potential dexamethasone-sparing regimen for glioblastoma: Spironolactone, ecallantide, clotrimazole.
- Immunotargeting and therapy of cancer by advanced multivalence antibody scaffolds.
- Efficacy, pharmacokinetics, and safety of icatibant for the treatment of Japanese patients with an acute attack of hereditary angioedema: A phase 3 open-label study.
- Icatibant, another piece of the therapeutic puzzle regarding hemodynamic side effects of angiotensin-converting enzyme inhibitors.
- Effect of icatibant on angiotensin-converting enzyme inhibitor-induced angioedema: A meta-analysis of randomized controlled trials.
- Self-administration of icatibant in acute attacks of Type I hereditary angioedema: A case report and review of hereditary angioedema.
- Novel Therapies for Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Systematic Review of Current Evidence.
- Long-term safety of icatibant treatment of patients with angioedema in real-world clinical practice.
- Outcomes after ecallantide treatment of laryngeal hereditary angioedema attacks
- Management of acute attacks of hereditary angioedema: role of ecallantide
- Icatibant outcome survey: patient experience with hereditary angioedema treatment
- Icatibant Exposure During Pregnancy in a Patient With Hereditary Angioedema.
- [Prophylactic use of icatibant before tracheal intubation of a patient with hereditary angioedema type III. (A literature review of perioperative management of patients with hereditary angioedema type III)].
- Hereditary angioedema therapy: kallikrein inhibition and bradykinin receptor antagonism
- Efficacy and safety of ecallantide in treatment of recurrent attacks of hereditary angioedema: open-label continuation study.
- Icatibant for the treatment of hereditary angioedema
- A review of icatibant for the treatment of hereditary angioedema
- [Administration of conestat alfa, human C1 esterase inhibitor and icatibant in the treatment of acute angioedema attacks in adults with hereditary angioedema due to C1 esterase inhibitor deficiency. Treatment comparison based on systematic review results].
- Ecallantide for treatment of acute hereditary angioedema attacks: analysis of efficacy by patient characteristics
- Immunotherapy for primary immunodeficiency diseases.
- A phase 2 prospective, randomized, double-blind trial comparing the effects of tranexamic acid with ecallantide on blood loss from high-risk cardiac surgery with cardiopulmonary bypass (CONSERV-2 Trial).
- Ecallantide for the treatment of hereditary angiodema in adults
- Response to ecallantide treatment of acute attacks of hereditary angioedema based on time to intervention: results from the EDEMA clinical trials
- Ecallantide (DX-88) for acute hereditary angioedema attacks: integrated analysis of 2 double-blind, phase 3 studies.
- Randomized placebo-controlled trial of the bradykinin B₂ receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial
- Successful long-term treatment with the bradykinin B2 receptor antagonist icatibant in a patient with hereditary angioedema
- Icatibant: first global approval
- Icatibant (Firazyr®) for the treatment of acute attacks in hereditary angioedema
- EDEMA4: a phase 3, double-blind study of subcutaneous ecallantide treatment for acute attacks of hereditary angioedema
- Ecallantide: its pharmacology, pharmacokinetics, clinical efficacy and tolerability.
- Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema
- Icatibant for hereditary angioedema
- Successful treatment of hereditary angioedema with bradykinin B2-receptor antagonist icatibant
- Critical role of kallikrein in hereditary angioedema pathogenesis: a clinical trial of ecallantide, a novel kallikrein inhibitor
- Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant)
- Novel pharmacotherapy of acute hereditary angioedema with bradykinin B2-receptor antagonist icatibant