0000000000266675
AUTHOR
Rui De Passos Sousa
Efficacy of Caplacizumab in Patients with aTTP in the HERCULES Study According to Baseline Disease Severity
Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening autoimmune thrombotic microangiopathy that involves abnormal processing of von-Willebrand factor (vWF) and results in multiple organ dysfunction. Although aTTP remains a very unpredictable disease, risk factors for death include older age, lactate dehydrogenase (LDH) levels >10x the upper limit of normal (ULN), and cerebral involvement (i.e., the French severity score) (Benhamou et al. Haematologica 2012;97:1181-1186). In addition, raised cardiac troponin-I (cTnI) levels of >2.5 µg/L have also been linked with a higher risk of mortality or refractoriness (Benhamou et al. J Thromb Haemost 2015;1…
Efficacy of Caplacizumab in Patients with aTTP in the HERCULES Study According to Initial Immunosuppression Regimen
Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is an acute, life-threatening thrombotic microangiopathy that requires urgent and specialized treatment. Prior to the introduction of caplacizumab, the treatment for aTTP was based on daily therapeutic plasma exchange (TPE; to replenish functional ADAMTS13 enzyme) plus immunosuppression (mainly corticosteroids and rituximab; to suppress anti-ADAMTS13 autoantibody production). TPE combined with immunosuppressive therapy improved outcomes in patients; however, episodes of aTTP are still associated with an acute mortality of up to 20% as these therapies do not have an immediate effect on the pathologic microvascular thrombosis. Th…
Long-Term Safety and Efficacy of Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura (aTTP): The Post-HERCULES Study
Abstract Background: The post-HERCULES trial (NCT02878603) evaluated long-term safety and efficacy of caplacizumab in patients with acquired thrombotic thrombocytopenic purpura (aTTP; also known as immune-mediated TTP), and efficacy of repeated use of caplacizumab for aTTP recurrence. Methods: Patients who completed the HERCULES trial were invited to participate in the post-HERCULES study and attend twice-yearly visits for 3 years. In case of aTTP recurrence, patients could receive open-label (OL) caplacizumab with therapeutic plasma exchange (TPE) and immunosuppression (IST). Safety was assessed during the overall study period (intention-to-observe [ITO] population) and during recurrences.…
Safety of Caplacizumab in Patients Without Documented Severe ADAMTS13 Deficiency During the HERCULES Study
Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening autoimmune thrombotic microangiopathy caused by a deficiency in the activity of ADAMTS13 leading to the formation of ultra-large multimers of von Willebrand factor (vWF) and abnormal platelet adhesion in the microvasculature. aTTP requires prompt diagnosis and rapid initiation of treatment to limit the risk of negative or fatal outcomes. The clinical diagnosis of aTTP is based on thrombocytopenia and microangiopathic hemolytic anemia and is confirmed by ADAMTS13 <10%. However, the latter confirmation is not always rapidly available, and treatment is typically initiated based on the clinical diagno…