Holger Hägele’s research while affiliated with University of Cologne and other places

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.

Background The anti-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 the majority of patients. Five patients experienced iTTP exacerbations or relapses that led to the resumption of daily caplacizumab application. VWF activity was repeatedly measured in 16 out of 25 patients and documented sufficient suppression by caplacizumab after 24 and 48 hours, in line with published pharmacodynamics. Conclusion Extension of caplacizumab application intervals from daily to alternate-day dosing may be safely considered in selected patients after three to four weeks of daily treatment. Earlier modifications may be discussed in low-risk patients, but require close monitoring for clinical and laboratory features of thrombotic microangiopathy.

Background: The anti-VWF nanobody caplacizumab directly prevents the fatal microthrombi formation in immune-mediated thrombotic thrombocytopenic purpura, thereby adding a new therapeutic principle to the treatment of this autoimmune 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 treatment approach in a retrospective cohort of 25 iTTP patients treated with caplacizumab in Austria and Germany between 2018 and 2021. Results: Alternate-day dosing of caplacizumab appeared feasible and led to persisting normal platelet counts in the majority of patients, who were converted after a median time of 17 days daily treatment. Four patients experienced iTTP exacerbations or relapses that led to the resumption of daily caplacizumab application and/or other therapies. VWF activity was repeatedly measured in 17 out of 25 patients and documented sufficient suppression by caplacizumab after 24 and 48 hours, in line with published pharmacokinetics. Conclusion: Extension of caplacizumab injection intervals from daily to alternate-day dosing may be safely considered in selected patients after 30 days of daily treatment. Earlier modifications may be considered in low-risk patients, but require close monitoring for clinical and laboratory features of thrombotic microangiopathy. Disclosures Völker: Sanofi-Genzyme: Honoraria, Other: counselling fees.