Real-world data confirm the effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura

Völker, Linus A.; Kaufeld, Jessica; Miesbach, Wolfgang; Brähler, Sebastian; Reinhardt, Martin; Kühne, Lucas; Mühlfeld, Anja; Schreiber, Adrian; Gaedeke, Jens; Tölle, Markus; Jabs, Wolfram J.; Özcan, Fedai; Markau, Silke; Girndt, Matthias; Bauer, Frederic; Westhoff, Timm H.; Felten, H; Hausberg, Martin; Brand, Marcus; Gerth, Jens; Bieringer, Markus; Bommer, Martin; Zschiedrich, Stefan; Schneider, Johanna; Elitok, Saban; Gawlik, Alexander; Gäckler, Anja; Kribben, Andreas; Schwenger, Vedat; Schoenermarck, Ulf; Roeder, Maximilian von; Radermacher, Jörg; Bramstedt, Jörn; Morgner, Anke; Herbst, Regina; Harth, Ana; Potthoff, Sebastian A.; Auer, Charis von; Wendt, Ralph T.; Christ, Hildegard; Brinkkoetter, Paul T.; Menne, Jan

doi:10.1182/bloodadvances.2020001973

Cited by 81 publications

(97 citation statements)

References 12 publications

(22 reference statements)

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“…Individual patient characteristics, treatment modalities, and individual courses comprising platelet counts and ADAMTS13 activity measurements and therapeutic interventions are reported in supplemental Table 1 and supplemental Figure 1 and are described in detail by Voelker et al 2 ADAMTS13 activity as a biomarker to guide treatment modalities ADAMTS13 activities were regularly assessed during caplacizumab treatment in 45 (75.0%) of 60 patients. The median time after diagnosis to final ADAMTS13 activity recovery to .10% was 32.5 (8-204) days and 21 (1-191) days after stopping PEX treatment (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

ADAMTS13 and VWF activities guide individualized caplacizumab treatment in patients with aTTP

et al. 2020

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Abstract Introduction of the nanobody caplacizumab was shown to be effective in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP) in the acute setting. The official recommendations include plasma exchange (PEX), immunosuppression, and the use of caplacizumab for a minimum of 30 days after stopping daily PEX. This study was a retrospective, observational analysis of the use of caplacizumab in 60 patients from 29 medical centers in Germany. Immunosuppressive treatment led to a rapid normalization of ADAMTS13 activities (calculated median, 21 days). In 35 of 60 patients, ADAMTS13 activities started to normalize before day 30 after PEX; in 11 of 60 patients, the treatment was extended beyond day 30; and in 5 patients, it was extended even beyond day 58 due to persistent autoimmune activity. In 34 of 60 instances, caplacizumab was stopped before day 30 with a favorable outcome whenever ADAMTS13 activities were >10%. In contrast, 11 of 34 patients with ADAMTS13 activities <10% at the time of stopping caplacizumab treatment developed a nonfavorable outcome (disease exacerbation or relapse). In some cases, prolongation of the treatment interval to every other day was feasible and resulted in a sustained reduction of von Willebrand factor activity. ADAMTS13 activity measurements are central for a rapid diagnosis in the acute setting but also to tailor disease management. An ADAMTS13 activity–guided approach seems safe for identifying the individual time point when to stop caplacizumab to prevent overtreatment and undertreatment; this approach will result in significant cost savings without jeopardizing the well-being of patients. In addition, von Willebrand factor activity may serve as a biomarker for drug monitoring.

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Section: Resultsmentioning

confidence: 99%

ADAMTS13 and VWF activities guide individualized caplacizumab treatment in patients with aTTP

et al. 2020

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“…Here, we report on six patients with an acute episode of aTTP treated with caplacizumab but without plasma exchange that were identified retrospectively from a cohort of 60+ patients treated with caplacizumab at 30+ different medical centers across Austria and Germany between 2018 and 2020. 9,10 All six patients were white females between 31 and 75 years of age (Table 1). There was no uniform protocol for TTP diagnosis and treatment and the use of caplacizumab, plasma exchange, or immunosuppression.…”

Section: Re Sults and Discussionmentioning

confidence: 99%

“…Here we report on seven episodes of aTTP, treated without plasma exchange, in six patients in Germany and Austria. Data were accessed retrospectively 9,10 . Laboratory parameters (blood cell counts, serum chemistry) were measured with local standard methods.…”

Section: Methodsmentioning

confidence: 99%

“…Data were accessed retrospectively. 9,10 Laboratory parameters (blood cell counts, serum chemistry) were measured with local standard methods. For measurement of ADAMTS13 activity and quantification of anti-AD-AMTS13 antibodies, various methods were used as locally available (ie, chromogenic ELISA techniques, FRETS-VWF73 assay, or anti-ADAMTS13-IgG antibody ELISA or Bethesda-assay, respectively).…”

Section: Me Thodsmentioning

confidence: 99%

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Treatment of acquired thrombotic thrombocytopenic purpura without plasma exchange in selected patients under caplacizumab

Völker

Brinkkoetter

Knöbl

et al. 2020

Journal of Thrombosis and Haemostasis

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“…Conversely, in a retrospective study gathering every patient treated by caplacizumab between June 2018 and December 2019 in Germany, caplacizumab was administered frontline in only 58% of patients and as a salvage therapy in the others. 21 In this study, none of the pa- Note: Although these studies respond to different designs and have different endpoints, data comparison is facilitated by the common definition of outcomes. Unlike the other studies, only 58% of patients received frontline caplacizumab in Völker's work.…”

Section: R Ati Onale and E Viden Ce For C Apl Acizumab In It Tpmentioning

confidence: 99%

Should all patients with immune‐mediated thrombotic thrombocytopenic purpura receive caplacizumab?

Picod¹,

Veyradier

Coppo

2021

Journal of Thrombosis and Haemostasis

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Immune‐mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life‐threatening disease that causes systemic platelet‐rich microthrombi with multiorgan damage. The historical treatment is based on therapeutic plasma exchange (TPE) and immunosuppression. Despite survival rates exceeding 85%, unfavorable outcomes including refractoriness, death, and exacerbations of the disease during treatment still calls for a better management strategy. Caplacizumab (Cablivi) appeared recently as a new treatment in iTTP. By inhibiting binding of von Willebrand factor to platelets, caplacizumab prevents platelets aggregation and the formation of microthrombi. Two pivotal randomized controlled trials have provided positive results where the use of caplacizumab is associated with faster platelet count recovery and less unfavorable outcomes. The other strength of this agent is an impressive alleviation in the burden of care, consisting in less TPE sessions and lower volumes of plasma to achieve remission, as well as substantial shortening in the length of hospitalization. However, since the recent approval of caplacizumab for the treatment of iTTP on the basis of these studies, debates remain regarding its systematic use in this indication. Should all patients be benefited from caplacizumab? Should we reserve caplacizumab only to the more severe patients? Should caplacizumab be initiated frontline or as a salvage therapy? If applicable, how should we select patients for caplacizumab? Last, is caplacizumab treatment cost‐effective? This review aims at addressing these specific questions at a time when iTTP is entering the area of targeted therapies.

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Real-world data confirm the effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura

Cited by 81 publications

References 12 publications

ADAMTS13 and VWF activities guide individualized caplacizumab treatment in patients with aTTP

ADAMTS13 and VWF activities guide individualized caplacizumab treatment in patients with aTTP

Treatment of acquired thrombotic thrombocytopenic purpura without plasma exchange in selected patients under caplacizumab

Should all patients with immune‐mediated thrombotic thrombocytopenic purpura receive caplacizumab?

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