Recombinant ADAMTS13 in Congenital Thrombotic Thrombocytopenic Purpura.

BACKGROUND: Congenital thrombotic thrombocytopenic purpura (TTP) results from severe hereditary deficiency of ADAMTS13. The efficacy and safety of recombinant ADAMTS13 and standard therapy (plasma-derived products) administered as routine prophylaxis or on-demand treatment in patients with congenital TTP is not known. METHODS: In this phase 3, open-label, crossover trial, we randomly assigned patients in a 1:1 ratio to two 6-month periods of prophylaxis with recombinant ADAMTS13 (40 IU per kilogram of body weight, administered intravenously) or standard therapy, followed by the alternate treatment; thereafter, all the patients received recombinant ADAMTS13 for an additional 6 months. The trigger for this interim analysis was trial completion by at least 30 patients. The primary outcome was acute TTP events. Manifestations of TTP, safety, and pharmacokinetics were assessed. Patients who had an acute TTP event could receive on-demand treatment. RESULTS: A total of 48 patients underwent randomization; 32 completed the trial. No acute TTP event occurred during prophylaxis with recombinant ADAMTS13, whereas 1 patient had an acute TTP event during prophylaxis with standard therapy (mean annualized event rate, 0.05). Thrombocytopenia was the most frequent TTP manifestation (annualized event rate, 0.74 with recombinant ADAMTS13 and 1.73 with standard therapy). Adverse events occurred in 71% of the patients with recombinant ADAMTS13 and in 84% with standard therapy. Adverse events that were considered by investigators to be related to the trial drug occurred in 9% of the patients with recombinant ADAMTS13 and in 48% with standard therapy. Trial-drug interruption or discontinuation due to adverse events occurred in no patients with recombinant ADAMTS13 and in 8 patients with standard therapy. No neutralizing antibodies developed during recombinant ADAMTS13 treatment. The mean maximum ADAMTS13 activity after recombinant ADAMTS13 treatment was 101%, as compared with 19% after standard therapy. CONCLUSIONS: During prophylaxis with recombinant ADAMTS13 in patients with congenital TTP, ADAMTS13 activity reached approximately 100% of normal levels, adverse events were generally mild or moderate in severity, and TTP events and manifestations were rare. (Funded by Takeda Development Center Americas and Baxalta Innovations; ClinicalTrials.gov number, NCT03393975.).

Management of Adult Patients with Primary Immune Thrombocytopenia (ITP) in Clinical Practice: A Consensus Approach of the Spanish ITP Expert Group.

BACKGROUND AND OBJECTIVE: Diagnosis and management of primary immune thrombocytopenia (ITP) have changed dramatically in the last decade. The aim of the study was to obtain information about the opinion of the Spanish ITP Group (GEPTI) members regarding the best clinical practices for diagnosis and management of adult patients with ITP. MATERIALS AND METHODS: A two-round Delphi method was carried out by sending to 129 experts a 90-item questionnaire developed by 11 specialists, with a 4-point Likert scale ("never," "sometimes," "frequently," and "always") for the assessment of responses. RESULTS: Forty out of the 129 experts participated in the survey (participation rate 30.2%) and 39 completed the questionnaire (response rate 97.5%). Salient consensus points included the following: the need to indicate workup studies from a sustained platelet count < 100 x 109/L in the absence of a clear etiology; bone marrow aspiration in elderly patients with suspected ITP; beginning treatment in asymptomatic patients with a platelet count < 20 x 109/L; not exceeding 6-7 weeks of corticosteroid therapy; switching from corticosteroids to one thrombopoietin receptor agonist (TRA); switching to other TRA or other options as combinations of them with immunosuppressive drugs in case of failure; how to reduce tapering TRA; treating patients with symptomatic persistent ITP and platelet count > 20 x 109/L; and considering mucosal or severe bleeding as a basic criterion for hospital admission. CONCLUSIONS: The present consensus document provides a reference framework for the management of patients with ITP in clinical practice.