Ecallantide for treatment of acute attacks of acquired C1 esterase inhibitor deficiency

Acquired C1 inhibitor (C1-INH) deficiency exposes patients to angioedema recurrences (acquired angioedema [AAE]) mediated by bradykinin pathway activation. C1-INH replacement and specific inhibition of plasma kallikrein with ecallantide have been successful in the treatment of hereditary angioedema (HAE), a more common related disorder. C1-INH replacement has also been used in the treatment of AAE, but because of the underlying mechanism of rapid catabolism, some patients may not respond. As part of preclinical investigation of ecallantide, a potent bradykinin pathway inhibitor, we evaluated three AAE patients treated successfully with that agent. This study was designed to assess ecallantide for treatment of attacks in AAE. Three patients with AAE were treated a total of 12 times with various dosing regimens of ecallantide based on the protocols established for the studies using ecallantide in HAE (Evaluation of DX-88's Effects in Mitigating Angioedema trials). Response to therapy was also based on outcome measures determined by these protocols. Ecallantide effectively relieved symptoms in three patients with various manifestations of AAE over 12 acute episodes. Kallikrein inhibition with ecallantide appears effective in the treatment of AAE and may be an alternative for patients with resistance to C1-INH replacement therapy.