ADAMTS13 and VWF activities guide individualized caplacizumab treatment in patients with aTTP

Blood Adv. 2020 Jul 14;4(13):3093-3101. doi: 10.1182/bloodadvances.2020001987.

Abstract

Introduction of the nanobody caplacizumab was shown to be effective in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP) in the acute setting. The official recommendations include plasma exchange (PEX), immunosuppression, and the use of caplacizumab for a minimum of 30 days after stopping daily PEX. This study was a retrospective, observational analysis of the use of caplacizumab in 60 patients from 29 medical centers in Germany. Immunosuppressive treatment led to a rapid normalization of ADAMTS13 activities (calculated median, 21 days). In 35 of 60 patients, ADAMTS13 activities started to normalize before day 30 after PEX; in 11 of 60 patients, the treatment was extended beyond day 30; and in 5 patients, it was extended even beyond day 58 due to persistent autoimmune activity. In 34 of 60 instances, caplacizumab was stopped before day 30 with a favorable outcome whenever ADAMTS13 activities were >10%. In contrast, 11 of 34 patients with ADAMTS13 activities <10% at the time of stopping caplacizumab treatment developed a nonfavorable outcome (disease exacerbation or relapse). In some cases, prolongation of the treatment interval to every other day was feasible and resulted in a sustained reduction of von Willebrand factor activity. ADAMTS13 activity measurements are central for a rapid diagnosis in the acute setting but also to tailor disease management. An ADAMTS13 activity-guided approach seems safe for identifying the individual time point when to stop caplacizumab to prevent overtreatment and undertreatment; this approach will result in significant cost savings without jeopardizing the well-being of patients. In addition, von Willebrand factor activity may serve as a biomarker for drug monitoring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS13 Protein
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Purpura, Thrombotic Thrombocytopenic* / drug therapy
  • Retrospective Studies
  • Single-Domain Antibodies
  • von Willebrand Factor*

Substances

  • Fibrinolytic Agents
  • Single-Domain Antibodies
  • von Willebrand Factor
  • caplacizumab
  • ADAMTS13 Protein
  • ADAMTS13 protein, human