New Therapeutic Targets and Treatment Options for Thrombotic Microangiopathy: Caplacizumab and Ravulizumab

Abstract

Objective To review the efficacy and safety of caplacizumab and ravulizumab for thrombotic microangiopathy. Data Sources A literature search from January 2011 to May 2020 was performed using the key terms caplacizumab (or ALX-0681), ravulizumab (or ALXN1210), atypical hemolytic uremic syndrome (aHUS), acquired thrombotic thrombocytopenic purpura (aTTP), and thrombotic microangiopathy. Study Selection and Data Extraction Relevant clinical trials and articles in the English language were identified and reviewed. Data Synthesis aTTP and aHUS are syndromes of thrombotic microangiopathy manifested by excessive platelet aggregation and endothelial cell destruction, with subsequent thrombocytopenia, hemolysis, and multiorgan failure. Current standard therapy for aTTP is therapeutic plasma exchange (TPE) to remove von Willebrand factor (vWF) multimers and anti-ADAMTS13 autoantibodies. As an adjunctive therapy to TPE, caplacizumab inhibits binding of vWF to platelets and prevents new microthrombi formation. It reduces thromboembolic event rate and days of TPE and delays relapse. Headache and epistaxis were the most common adverse events. aHUS develops because of dysregulation of the alternative complement pathway, followed by constitutive activation of complement components that causes thrombosis and end-organ damage. Short-term initial evaluation with ravulizumab, a long-acting complement inhibitor, demonstrates rapid hematological and renal improvement, with sustained complement inhibition and tolerable adverse effects. Relevance to Patient Care and Clinical Practice This review describes the pharmacology, pharmacokinetics, cost consideration, and clinical studies for caplacizumab and ravulizumab for thrombotic microangiopathy. Place of therapy is also discussed. Conclusion Targeted therapies with caplacizumab and ravulizumab are expected to reduce the burden of exacerbation, refractory disease, recurrence, and possibly death for thrombotic microangiopathy.