Alternate‐day dosing of caplacizumab for immune‐mediated thrombotic thrombocytopenic purpura

Abstract

Background:The anti-von Willebrand factor (VWF) nanobody caplacizumab directly prevents the fatal microthrombi formation in immune-mediated thrombotic thrombocytopenic purpura (iTTP), thereby adding a new therapeutic principle to the treatment of this disorder. However, real-world treatment modalities beyond clinical trials remain heterogeneous.Methods: Here, we describe the risks and benefits of an alternate-day dosing regimen for caplacizumab by thoroughly analyzing the timing and outcome of this approach in a retrospective cohort of 25 iTTP patients treated with caplacizumab at seven different medical centers in Austria and Germany between 2018 and 2021.Results: Alternate-day dosing of caplacizumab appeared feasible and led to persisting normal platelet counts in most patients. Five patients experienced iTTP exacerbations or relapses that led to the resumption of daily caplacizumab application. VWF activityThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

100 Years of Thrombotic Thrombocytopenic Purpura: A Story of Death and Life

“…In addition, the steep learning curve with caplacizumab enabled considerations on individualized, pathophysiology-based therapy, not adhering to the strict labeling. [143][144][145][146][147][148][149] Today, caplacizumab has been established as the first-line therapy of immune TTP in many centers as recommended in current guidelines. 51,88,94,144,145,150 Milestone 5: Individualized TTP Treatment Considering all these fundamental innovations in TTP management, a redefinition of outcome parameters was necessary.…”

A British Society for Haematology Guideline: Diagnosis and management of thrombotic thrombocytopenic purpura and thrombotic microangiopathies

“…40 Caplacizumab is being used in acute TTP without the need for PEX 43 and alternate-day regimens. 44 Caplacizumab causes a significant reduction in VWF activity and is associated with bleeding, which is rarely severe. Major bleeding can be managed with VWF concentrate.…”

“…Persistence of severe ADAMTS13 deficiency is associated with clinical relapse; therefore, caplacizumab may be continued beyond 30 days following cessation of PEX if ADAMTS 13 activity levels remain <10 iu/dL 40 . Caplacizumab is being used in acute TTP without the need for PEX 43 and alternate‐day regimens 44 …”

Diagnosis and treatment of thrombotic microangiopathy

“…Caplacizumab should be started before PE and then continue daily until 30 days after PE completion 13 . Caplacizumab is an expensive drug (approximate 270 000 dollars per treatment) and methods to individualize treatment are being investigated, such as alternative day dosing or reducing the initial course 17 . Volker et al found that monitoring ADAMTS13 activity allowed clinicians to individualize treatment by shortening or extending caplacizumab duration with successful outcomes 18 .…”

“…13 Caplacizumab is an expensive drug (approximate 270 000 dollars per treatment) and methods to individualize treatment are being investigated, such as alternative day dosing or reducing the initial course. 17 Volker et al found that monitoring ADAMTS13 activity allowed clinicians to individualize treatment by shortening or extending caplacizumab duration with successful outcomes. 18 The study concluded that most aTTP patients could have a shorter duration of caplacizumab treatment but 20% would benefit from a longer duration.…”