Natural History and Treatment Outcomes of Congenital Thrombotic Thrombocytopenic Purpura: A Retrospective Longitudinal Cohort Study.

Background: Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare, life-threatening thrombotic disorder. The real-world clinical trajectory and management of cTTP are not well defined. Objectives: Describe patient characteristics, quantify the incidence and prevalence of clinical manifestations and disease-related complications, and describe treatment patterns and treatment-related outcomes of patients with cTTP. Methods: In this retrospective, multinational, longitudinal cohort study, data were abstracted from the medical records of patients with severe hereditary ADAMTS13 deficiency (<10% activity) at 9 participating sites across Europe and the United States. Eligible patients experienced an index event (cTTP diagnosis, an acute TTP event or TTP manifestation, a cTTP-related clinical event, or prophylaxis) between January 1, 2009, and December 31, 2017. Data collection was from January 1, 2009, to December 31, 2020. A post hoc analysis was conducted among patients who matched inclusion criteria for a phase 3 trial (NCT03393975), and who received plasma-based therapy (PBT) prophylaxis at least once per month, up to 3 times per week. Results: Medical records from 78 patients (61 [78.2%] female) were included in the study. The mean (SD) follow-up was 8.1 (3.1) years. Ninety-two acute TTP events were recorded in 55 (70.5%) patients (overall event rate, 0.145 events per person-year). Eighty (87.0%) acute TTP events occurred in the absence of prophylactic treatment, of which 16 (20.0%) resulted in organ damage (based on physicians' assessment). Twelve (13.0%) acute TTP events occurred during prophylaxis; none resulted in organ damage. Sixty-four TTP manifestations were recorded in 29 (37.2%) patients (overall event rate, 0.101 events per person-year). Of the 25 patients in the post hoc analysis, 4 experienced 9 acute TTP events while receiving PBT prophylaxis. Conclusions: Our findings suggest that acute TTP events occurred less frequently during periods of prophylaxis but also highlight prophylaxis' intrinsic limitations in preventing ongoing manifestations, cumulative organ damage, and the logistical and safety burdens associated with repeated plasma infusions. Patients with cTTP bear a substantial clinical and disease burden associated with acute TTP events and organ damage. Despite treatment with PBT prophylaxis, some patients still experienced acute TTP events, suggesting that more effective treatments may be needed.