Presentation Details
| Clinical Outcomes of Congenital Thrombotic Thrombocytopenic Purpura with and without Prophylaxis Therapy: a Multinational Chart Review Study Paul Coppo1, Marie Scully2, Johanna A Kremer Hovinga3, Maria Jose Aragon4, Parth Patwari5, Linda T Wang5, Björn Mellgård5, Ragy Saad5. 1APHP.6–Reference Center for Thrombotic Microangiopathies (CNR-MAT), Hôpital St Antoine, Paris, France.2University College London Hospitals NHS Foundation Trust, London, United Kingdom.3Department of Hematology and Central Hematology Laboratory, Bern University Hospital, Bern, Switzerland.4HCD Economics, Knutsford, United Kingdom.5Takeda Development Center Americas, Inc., Cambridge, MA, USA |
Abstract
Background: Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare, life-threatening genetic disorder characterized by severe deficiency of ADAMTS13, the von Willebrand factor–cleaving protease. This results in the formation of platelet-rich microthrombi, leading to platelet consumption and thrombocytopenia. Current treatment strategies focus on replenishing ADAMTS13 through plasma-based therapy. Objectives: The primary study objectives were to describe the characteristics of patients with cTTP, as well as the prevalence and incidence of clinical manifestations of cTTP and its complications. The secondary objectives were to explain the treatment patterns, treatment-related outcomes, and healthcare resource utilization in patients with cTTP. Treatment patterns and treatment-related outcomes are reported here. Methods: This retrospective chart review was conducted in nine sites across Europe, the United Kingdom, and the United States. Patient-level data were abstracted from medical records from January 1, 2009, through December 31, 2020. Patients with cTTP were included if they experienced any of the following events from January 1, 2009, through December 31, 2017 (index identification period): cTTP diagnosis, prophylactic or on-demand treatment for cTTP, or another cTTP-related major clinical event. Patients were followed from the date of the first qualifying event (study index date) until loss to follow-up, enrollment in a clinical trial, end of the study period, or death. Results were summarized descriptively and stratified by follow-up time periods with and without prophylaxis exposure; patients may contribute patient-time to both periods, but never concurrently. Ethics approval and informed consent were obtained where applicable. Results: The study included 78 patients, with a mean (SD) follow-up of 8.1 (3.1) years. Most patients were female (78.2%), including 45 with ≥1 reported pregnancy at any time. The mean (SD) age at initial cTTP diagnosis and study index was 26.2 (17.3) years and 29.5 (15.7) years, respectively. Prophylaxis was initiated 65 times in 47 (60.3%) patients. The most common reasons for initiation were clinical symptoms and pregnancy (both n=13/47; 27.7%). The mean (SD) duration of therapy was 3.9 (4.3) years; 41 (63.1%) treatments were stopped or interrupted (Table 1). A total of 92 acute events were reported by 55 (70.5%) patients during the study (0.145 episodes per person-year [PPY]). Fewer acute events occurred during prophylaxis treatment (n=12/92; 0.050 events PPY) than when patients were not receiving prophylaxis (n=80/92; 0.202 events PPY). Most events (11/12; 91.7%) occurring during prophylaxis exposure resolved without complications, and 50% (6/12) resolved in ≤7 days. Proportionally fewer events occurring outside prophylaxis exposure periods resolved without complications (59/80; 73.8%) and resolved in ≤7 days (25/80; 31.3%). Two patients died during an acute event, one each during prophylaxis exposure and non-exposure periods. Conclusions: There were fewer acute events and improved event resolution without complications during prophylaxis exposure periods. While these findings suggest the benefit of and support the use of prophylactic therapies to mitigate the substantial clinical burden of cTTP, persistent disease manifestations, despite plasma-based prophylaxis, suggest that challenges with existing treatments persist (Schraner, 2023, Blood), highlighting the need for novel therapies with demonstrated clinical safety and efficacy.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.