Efficacy of recombinant human C1 esterase inhibitor for the treatment of severe hereditary angioedema attacks.

BACKGROUND

Severe attacks of hereditary angioedema (HAE) are debilitating and potentially life threatening, and can increase anxiety and the use of medical resources.

OBJECTIVE

This post hoc assessment evaluated recombinant human C1 esterase inhibitor (rhC1-INH) used to treat acute severe HAE attacks.

METHODS

In a double-blind, randomized-controlled trial (RCT), patients with an HAE attack (baseline visual analog scale score of ≥50 mm, with severe attacks defined as ≥75 mm) were randomly assigned to receive rhC1-INH (50 IU/kg for patients who weighed <84 kg; 4200 IU for patients who weighed ≥84 kg) or placebo. Also, in an open-label extension (OLE) study of rhC1-INH, oropharyngeal-laryngeal attacks were analyzed. Rescue therapy with rhC1-INH 50 IU/kg (≤4200 IU) was permitted after 4 hours or for life-threatening symptoms (in the RCT) or after 1 hour (in the OLE study). The primary end point measured the time to the beginning of symptom relief by using the Treatment Effects Questionnaire.

RESULTS

Of 75 adults in the RCT, 43 had severe attacks and received either rhC1-INH (n = 24) or placebo (n = 19). The median (95% confidence interval) time to the onset of symptom relief totaled 90.0 minutes (95% confidence interval, 47.0-120.0 minutes) versus 334.0 minutes (95% confidence interval, 105.0 to not calculable minutes; hazard ratio, 2.5; p = 0.02), for rhC1-INH and placebo, respectively. Open-label rhC1-INH rescue therapy was administered to 1 of 24 in the rhC1-INH group (4.2%) and 10 of 19 in the placebo group (52.6%). During the OLE study, the median onset of symptom relief with rhC1-INH for eight oropharyngeal-laryngeal HAE attacks was 69.0 minutes (95% confidence interval, 59.0-91.0 minutes).

CONCLUSION

In the current study, rhC1-INH was efficacious in resolving severe HAE attacks, including oropharyngeal-laryngeal attacks. The rhC1-INH rescue treatment rapidly improved symptoms for patients who received placebo and who experienced worsening or sustained symptoms.