Long-term follow-up of patients treated with caplacizumab and safety and efficacy of repeat caplacizumab use: Post-HERCULES study

J Thromb Haemost. 2022 Dec;20(12):2810-2822. doi: 10.1111/jth.15892. Epub 2022 Oct 21.


Introduction: Caplacizumab demonstrated efficacy and safety in patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) in the phase 3 HERCULES trial. However, data on long-term outcomes following caplacizumab treatment are limited.

Objectives: The post-HERCULES trial (NCT02878603) evaluated long-term outcomes of patients with iTTP treated with caplacizumab in HERCULES and safety and efficacy of repeated caplacizumab use.

Patients/methods: Over 3 years of follow-up, patients could receive open-label caplacizumab with therapeutic plasma exchange (TPE) and immunosuppressive therapy (IST) in case of recurrence. Adverse events (AEs) were assessed during the overall study period (intention-to-observe [ITO] population) and during recurrences (recurrence population). TTP-related events (TTP-related death, recurrence, major thromboembolic events) were assessed in the efficacy ITO population (patients without recurrence during HERCULES or before post-HERCULES).

Results: Among 104 enrolled patients, incidences of AEs and serious AEs were similar between patients who had received caplacizumab + TPE + IST during HERCULES (n = 75) and those treated with placebo + TPE + IST (placebo; n = 29). TTP-related events occurred in 8% of patients (4/49) randomized to caplacizumab during HERCULES versus 38% (11/29) randomized to placebo. Nineteen patients had ≥1 recurrence; 13 of these were treated with caplacizumab. The first recurrence episode was resolved or resolving for all patients treated with caplacizumab, including nine patients with repeat caplacizumab use. All second recurrences (6/6) were resolved. Safety profile of caplacizumab for treatment of recurrence was consistent with HERCULES; most bleeding events were nonserious. No major cases of organ dysfunction were observed.

Conclusions: Long-term follow-up supports the safety and efficacy of caplacizumab for iTTP and its repeated use for recurrences.

Keywords: blood platelets; caplacizumab; follow-up studies; thrombotic thrombocytopenic purpura; von Willebrand factor.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS13 Protein / therapeutic use
  • Follow-Up Studies
  • Humans
  • Purpura, Thrombotic Thrombocytopenic*
  • Single-Domain Antibodies* / therapeutic use


  • ADAMTS13 Protein
  • caplacizumab
  • Single-Domain Antibodies
  • thiamine triphosphorate

Associated data

  • ClinicalTrials.gov/NCT02878603