Table 3.
Clinical studies of agents used in the treatment of hereditary angioedema
| Trial design | Primary efficacy outcome result | AE | Other safety notes | |
| Routine prophylaxis | ||||
| CINRYZE[34] C1 inhibitor (human) (1000 units every 3-4 d for 12 wk) IV | Randomized, double-blind, placebo-controlled, cross-over study (n = 24) | Decreased the number of attacks (mean 12.7 for placebo vs 6.1, P < 0.0001) | Sinusitis, rash, headache, upper respiratory tract infection | Precautions: hypersensitivity reactions, thrombotic events, and risk of transmission of infectious agents |
| DANOCRINE[35,36] Danazol (range, 40-1000 mg, mean: 171.2 mg/d) oral route | Retrospective (n = 118) | Decreased the number of attacks (33.3 per year when untreated vs 9.7 per year when treated) | Clinical: weight gain, menstrual irregularities, virilization in women, headache | 8 patients with long-term therapy had serious adverse events (i.e. myocardial infarction, stroke, deep vein thrombosis, acute pancreatitis, hepatocellular adenoma) |
| Laboratory: elevated liver enzymes, elevated cholesterol | Warnings: use in pregnancy is contraindicated. Thrombotic events, peliosis hepatis, benign hepatic adenoma, and intracranial hypertension have been reported | |||
| Acute attacks | ||||
| BERINERT[37] C1 esterase inhibitor (human) (10 or 20 units/kg body weight) IV | Randomized, double-blind, placebo-controlled study (n = 124) | 20 mg/kg dose: reduction in time to onset of symptom relief (> 4 h for placebo vs 50 min, P = 0.0016) | Headache, nausea, abdominal pain, dysgeusia, vomiting | Treatment-emergent AEs: laryngeal edema, facial attack with laryngeal edema, swelling (shoulder and chest) exacerbation of HAE, and laryngospasm |
| Precautions: hypersensitivity reactions, thrombotic events, and risk of transmission of infectious agents | ||||
| FIRAZYR[38,39] Icatibant (30 mg) SQ | Randomized, double-blind, comparator-group study [n = 56 (placebo comparator study)] [n = 74 (tranexamic acid comparator study)] | Decreased time to onset of symptom relief (4.6 h placebo vs 2.5 h, P = 0.142; 12 h tranexamic acid vs 2 h, P < 0.001 ) | Injection site reactions; common events include recurrent attacks, nausea, abdominal pain, headache, asthenia, rash | Precautions: caution should be used in patients with acute ischemic heart disease or unstable angina pectoris, and in patients in the weeks following a stroke |
| KALBITOR[40] Ecallantide (30 mg) SQ | Randomized, double-blind, placebo-controlled trial (n = 96) | Decreased symptom severity measured by Mean Symptom Complex Severity scores (-0.4 placebo vs -0.8, P = 0.010) | Headache, nausea, diarrhea, pyrexia, injection site reactions, nasopharyngitis | Warnings: hypersensitivity reactions, including anaphylaxis |
| KALBITOR[40] Ecallantide (30 mg) SQ | Randomized, double-blind, placebo-controlled trial (n = 72) | Improved symptom response to treatment measured by Treatment Outcome Scores (36 placebo vs 63, P = 0.045) |
AE: Adverse events; HAE: Hereditary angioedema; SQ: By subcutaneous route.