Tailoring caplacizumab administration using ADAMTS13 activity for immune-mediated thrombotic thrombocytopenic purpura

Abstract

Caplacizumab, a nanobody targeting the A1 domain of von Willebrand factor (VWF), rapidly inhibits VWF interaction with platelets. This inhibition effectively prevents microthrombus formation and has led to its increasing use as a frontline disease-modifying agent. Clinical trial and postmarketing data suggest that caplacizumab administration guided by ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) recovery may be as effective and possibly safer than the dosing recommended by the manufacturer. Accordingly, this before-after cohort study sought to compare historical cases of immune thrombotic thrombocytopenic purpura (iTTP) (20 episodes) managed without caplacizumab with cases of iTTP (20 episodes) using a tailored approach to caplacizumab administration based on ADAMTS13 activity measured twice weekly during the hospital stay. Caplacizumab was discontinued when the ADAMTS13 activity was ≥20% on 2 consecutive occasions. Caplacizumab-treated patients received 6 doses (range, 2-30), an 81% reduction relative to the number of doses based on the manufacturer’s recommendations (35+), leading to cost savings of $6 466 800. Platelet count normalization occurred at 4 days in caplacizumab-treated patients vs 6 days in the non-caplacizumab cohort (P = .2). Rates of exacerbation and relapse were similar between both groups. Ultimately, these findings suggest that tailoring caplacizumab administration based on ADAMTS13 activity recovery leads to a marked reduction in the caplacizumab doses required. Despite this reduction, clinical and laboratory data were similar to those described in clinical trials and postmarketing studies while generating significant cost savings. Given these findings, prospective studies using ADAMTS13 activity to guide individualized caplacizumab therapy are warranted.