Essentials Acquired thrombotic thrombocytopenic purpura (aTTP) is linked with 
significant morbidity/mortality. Caplacizumab's effect on major thromboembolic 
(TE) events, exacerbations and death was studied. Fewer caplacizumab-treated 
patients had a major TE event, an exacerbation, or died versus placebo. 
Caplacizumab has the potential to reduce the acute morbidity and mortality 
associated with aTTP.
SUMMARY: Background Acquired thrombotic thrombocytopenic purpura (aTTP) is a 
life-threatening autoimmune thrombotic microangiopathy. In spite of treatment 
with plasma exchange and immunosuppression, patients remain at risk for 
thrombotic complications, exacerbations, and death. In the phase II TITAN study, 
treatment with caplacizumab, an anti-von Willebrand factor Nanobody® was shown 
to reduce the time to confirmed platelet count normalization and exacerbations 
during treatment. Objective The clinical benefit of caplacizumab was further 
investigated in a post hoc analysis of the incidence of major thromboembolic 
events and exacerbations during the study drug treatment period and thrombotic 
thrombocytopenic purpura-related death during the study. Methods The 
Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) 
for 'embolic and thrombotic events' was run to investigate the occurrence of 
major thromboembolic events and exacerbations in the safety population of the 
TITAN study, which consisted of 72 patients, of whom 35 received caplacizumab 
and 37 received placebo. Results Four events (one pulmonary embolism and three 
aTTP exacerbations) were reported in four patients in the caplacizumab group, 
and 20 such events were reported in 14 patients in the placebo group (two acute 
myocardial infarctions, one ischemic stroke, one hemorrhagic stroke, one 
pulmonary embolism, one deep vein thrombosis, one venous thrombosis, and 13 aTTP 
exacerbations). Two of the placebo-treated patients died from aTTP during the 
study. Conclusion In total, 11.4% of caplacizumab-treated patients and 43.2% of 
placebo-treated patients experienced one or more major thromboembolic events, 
experienced an exacerbation, or died. This analysis shows the potential for 
caplacizumab to reduce the risk of major thromboembolic morbidities and 
mortality associated with aTTP.