Diagnosis and management of angioedema with abdominal involvement: A gastroenterology perspective

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.