|Faster reconstitution of platelet count by caplacizumab in TTP|
|Acquired thrombotic thrombocytopenic purpura (TTP), characterized by unrestrained adhesion of von Willebrand factor aggregating and consuming platelet to form microvascular thrombosis, is caused by autoantibodies against the von Willebrand factor-cleaving protease ADAMTS13. This condition may cause thromboembolic events and even death. The current therapeutic strategy is daily plasma exchange in order to supply ADAMTS13 and remove von Willebrand factor as well as autoantibodies, in addition to immunosuppression. However, many patients fail to increase the platelet count upon treatment. Caplacizumab, a humanized variable-domain-only immunoglobulin fragment against von Willebrand factor, can inhibit the interaction between von Willebrand factor and platelets to prevent microvascular thrombosis. As the effectiveness of caplacizumab has been tested in a phase 2 study, the HERCULES investigators conduct this phase 3 trial and published the data in a recent issue of the NEJM (here).
A total of 145 patients were recruited to the study, among whom 72 individuals were assigned to the caplacizumab, whereas 73 participants were assigned to the placebo group. Individuals received a loading dose of caplacizumab (10mg) or placebo intravenously, and a subsequent dose of 10mg once daily subcutaneously until 30 days after the last daily plasma exchange (an extension up to 28 days beyond the 30-day threshold was permitted). The primary end point was the time to a response defined as gaining a normal platelet count (>150,000/mm3).
The median time to gaining a normal platelet count was significantly shorter in the caplacizumab group than that in the placebo group (2.69 days v.s. 2.88 days, p=0.01). Patients in the caplacizumab were 1.55 times as likely to have a normal platelet count as those in the placebo group. Moreover, the incidence of TPP-related negative events (death, recurrence, thromboembolic events, and refractory) was lower in the caplacizumab group (12% v.s. 38%, p<0.001). The major adverse event was mucocutaneous bleeding. In conclusion, treatment with caplacizumab in patients with TPP had a shorter time of reconstitution of a normal platelet count and a reduced incidence of TPP-related negative outcomes. Monitoring ADAMTS13 activity was valuable to guide discontinuation of caplacizumab.
This study was supported by a pharmaceutical company.