Recombinant ADAMTS13: An Enzyme Replacement Therapy for the Management of Congenital Thrombotic Thrombocytopenic Purpura

Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare autosomal recessive condition that causes deficiency of the von Willebrand factor (vWF)-cleaving metalloprotease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Traditionally, cTTP has been managed with plasma infusions, whether in the acute or prophylactic settings; however, there are various limitations and risks associated with this treatment modality. Recombinant ADAMTS13 (rADAMTS13) is the first FDA-approved product for management of cTTP. A phase III study compared rADAMTS13 to standard of care in which patients initially received prophylactic rADAMTS13 or plasma therapy, then crossed over to the alternative therapy. Patients receiving prophylactic rADAMTS13 had no acute cTTP events and lower rates of cTTP manifestations compared to standard of care. This article reviews the pharmacology, pharmacokinetics, efficacy, safety, dosing, administration, and implications for advanced practitioners of rADAMTS13 for the management of cTTP.