C1-inhibitor concentrate for individual replacement therapy in patients with severe hereditary angioedema refractory to danazol prophylaxis.
BACKGROUND
Hereditary angioedema (HAE) caused by functional deficiency of C1-inhibitor (C1-INH) is a rare disease that manifests with recurrent spontaneous nonallergic edema of the subcutaneous tissues and mucous membranes. In cases of laryngeal edema that are not treated immediately, HAE is associated with high mortality rates. Attenuated androgens (e.g., danazol) are usually administered for prophylaxis, but associated side effects may limit their use. This study investigated the efficacy, safety, and quality of life (QoL) associated with a pasteurized plasma-derived C1-inhibitor (pC1-INH) concentrate for individual replacement therapy (IRT) in patients with severe HAE suffering from frequent attacks who were intolerant or not responding to danazol.


METHODS
Twenty-two patients with severe HAE and danazol incompatibility or insufficient efficacy of danazol were recruited. Intraindividual comparisons of efficacy, safety, and QoL with pC1-INH concentrate IRT versus danazol treatment were made using retrospective and prospective patient data. Pharmacokinetic data were collected for 15 of the 22 patients.


RESULTS
In patients receiving pC1-INH regularly, the median number of attacks per year decreased significantly compared to danazol prophylaxis (p < 0.001), and the 24 laryngeal edema episodes per year ceased. Superior efficacy of pC1-INH was found for all QoL variables (e.g., general condition, social activities). No transmission of human immunodeficiency virus or hepatitis A, B, or C was observed.


CONCLUSIONS
In patients with severe HAE who experience severe side effects and/or lack of efficacy of danazol prophylaxis, very early substitution with pC1-INH can completely abolish the incidence of potentially fatal laryngeal edema and can reduce the incidence of acute attacks.
Kreuz
Wolfhart
W
Department of Haematology, Johann-Wolfgang-Goethe-University Hospital, Centre of Paediatrics III, Frankfurt am Main, Germany. Wolfhart.Kreuz@kgu.de
Martinez-Saguer
Inmaculada
I
Aygören-Pürsün
Emel
E
Rusicke
Eva
E
Heller
Christine
C
Klingebiel
Thomas
T
D000328:Adult; D054179:Angioedemas, Hereditary / Q000188:drug therapy* / Q000517:prevention & control*; D050718:Complement C1 Inhibitor Protein / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051056:Complement Inactivating Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003613:Danazol / Q000627:therapeutic use*; D004351:Drug Resistance / Q000502:physiology; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D050718:Complement C1 Inhibitor Protein; D051056:Complement Inactivating Agents; D004965:Estrogen Antagonists; D003613:Danazol