Iptacopan in C5 blockade refractory atypical hemolytic uremic syndrome with associated Castleman's disease: case...

Atypical Hemolytic Uremic Syndrome (aHUS) is a life-threatening disease related to mutations in the complement system. We report the first known case of the use of factor B inhibition in a 21-year-old male with complement-mediated thrombotic microangiopathy (CMTMA), later found to have Castleman's disease as a mimicker of aHUS.

Initially, the patient partially responded to eculizumab and then fully to ravulizumab. However, two years later, he experienced a flare that did not improve with ravulizumab redosing. An application for the compassionate use of Iptacopan was approved by the United States Food and Drug Administration, based on its success in C5 blockade Paroxysmal Nocturnal Hemoglobinuria. The patient's blood counts recovered, his microangiopathic hemolytic anemia ceased, and his acute kidney injury resolved allowing cessation of renal replacement therapy. Human Anti-murine anti-drug antibodies were suspected as the cause of C5 blockade failure but were unconfirmed. Ten months later, the patient's aHUS relapsed and he was concurrently diagnosed with Castleman's syndrome, a mimicker of aHUS, prompting the initiation of dual combination therapy of C5 blockade inhibitor and Factor B inhibitor and siltuximab.

This case marks the first use of Iptacopan for aHUS/CMTMA and the first use of dual combination therapy of eculizumab and Factor B Inhibition for patients with aHUS/CMTMA and Castleman's disease in the United States at the University of California Irvine by our thrombotic microangiopathy assessment team.

N/A, this study is not a clinical trial.