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Cold agglutinin disease (CAD) is characterized by immunoglobulin M autoantibodies, which bind red cells, activate the classical complement cascade, and lead to extravascular hemolysis. Previously, the terminal complement inhibitor eculizumab was shown to provide only minimal improvement in hemoglobin in CAD patients (Blood Adv 2018; 2:2543).
To test whether upstream complement inhibition with the anti-C1s antibody sutimlimab would more effectively abrogate hemolysis, investigators conducted a first-in-human trial in which 10 CAD patients (median duration of disease, 5 years) received three infusions of sutimlimab: a test dose (10 mg/kg) and a full dose (60 mg/kg) 1 to 4 days later followed by three weekly full doses. All patients were vaccin…