Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis

Blood Adv. 2021 Apr 27;5(8):2137-2141. doi: 10.1182/bloodadvances.2020001834.


The efficacy and safety of caplacizumab in individuals with acquired thrombotic thrombocytopenic purpura (aTTP) have been established in the phase 2 TITAN and phase 3 HERCULES trials. Integrated analysis of data from both trials was conducted to increase statistical power for assessing treatment differences in efficacy and safety outcomes. Caplacizumab was associated with a significant reduction in the number of deaths (0 vs 4; P < .05) and a significantly lower incidence of refractory TTP (0 vs 8; P < .05) vs placebo during the treatment period. Consistent with the individual trials, treatment with caplacizumab resulted in a faster time to platelet count response (hazard ratio, 1.65; P < .001), a 72.6% reduction in the proportion of patients with the composite end point of TTP-related death, TTP exacerbation, or occurrence of at least 1 treatment-emergent major thromboembolic event during the treatment period (13.0% vs 47.3%; P < .001), and a 33.3% reduction in the median number of therapeutic plasma exchange days (5.0 vs 7.5 days) vs placebo. No new safety signals were identified; mild mucocutaneous bleeding was the main safety finding. This integrated analysis provided new evidence that caplacizumab prevents mortality and refractory disease in acquired TTP and strengthened individual trial findings, with a confirmed favorable safety and tolerability profile. These trials were registered at as #NCT01151423 and #NCT02553317.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Plasma Exchange
  • Purpura, Thrombotic Thrombocytopenic* / drug therapy
  • Single-Domain Antibodies*


  • Fibrinolytic Agents
  • Single-Domain Antibodies
  • caplacizumab

Associated data