Impact of first-line use of caplacizumab on treatment outcomes in immune thrombotic thrombocytopenic purpura

Item Type:	Article
Title:	Impact of first-line use of caplacizumab on treatment outcomes in immune thrombotic thrombocytopenic purpura
Creators Name:	Völker, L.A. and Kaufeld, J. and Balduin, G. and Merkel, L. and Kühne, L. and Eichenauer, D.A. and Osterholt, T. and Hägele, H. and Kann, M. and Grundmann, F. and Kolbrink, B. and Schulte, K. and Gäckler, A. and Kribben, A. and Boss, K. and Potthoff, S.A. and Rump, L.C. and Schmidt, T. and Mühlfeld, A.S. and Schulmann, K. and Hermann, M. and Gaedeke, J. and Sauerland, K. and Bramstedt, J. and Hinkel, U.P. and Miesbach, W. and Bauer, F. and Westhoff, T.H. and Bruck, H. and Buxhofer-Ausch, V. and Müller, T.J. and Wendt, R. and Harth, A. and Schreiber, A. and Seelow, E. and Tölle, M. and Gohlisch, C. and Bieringer, M. and Geuther, G. and Jabs, W.J. and Fischereder, M. and von Bergwelt-Baildon, A. and Schönermarck, U. and Knoebl, P. and Menne, J. and Brinkkoetter, P.T.
Abstract:	BACKGROUND: The von Willebrand factor-directed nanobody caplacizumab has greatly changed the treatment of immune thrombotic thrombocytopenic purpura (iTTP) in recent years. Data from randomized controlled trials established efficacy and safety. OBJECTIVES: This study aims to address open questions regarding patient selection, tailoring of therapy duration, obstacles in prescribing caplacizumab in iTTP, effect on adjunct treatment, and outcomes in the real-world setting. METHODS: We report retrospective, observational cohorts of 113 iTTP episodes treated with caplacizumab and 119 historical control episodes treated without caplacizumab. We aggregated data from the caplacizumab phase II/III trials and real-world data from France, the United Kingdom, Germany, and Austria (846 episodes, 396 treated with caplacizumab, and 450 historical controls). RESULTS: Caplacizumab was efficacious in iTTP, independent of the timing of therapy initiation, but curtailed the time of active iTTP only when used in the first-line therapy within 72 hours after diagnosis and until at least partial ADAMTS13-activity remission. Aggregated data from multiple study populations showed that caplacizumab use resulted in significant absolute risk reduction of 2.87% for iTTP-related mortality (number needed to treat 35) and a relative risk reduction of 59%. CONCLUSION: Caplacizumab should be used in first line and until ADAMTS13-remission, lowers iTTP-related mortality and refractoriness, and decreases the number of daily plasma exchange and hospital stay. This trial is registered at www.clinicaltrials.gov as #NCT04985318.
Keywords:	Purpura, Thrombotic Thrombocytopenic, Thrombotic Microangiopathies, Observational Study, Von Willebrand Factor, ADAMTS13 Protein
Source:	Journal of Thrombosis and Haemostasis
ISSN:	1538-7933
Publisher:	Elsevier
Volume:	21
Number:	3
Page Range:	559-572
Date:	March 2023
Official Publication:	https://doi.org/10.1016/j.jtha.2022.11.010
PubMed:	View item in PubMed

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