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

被引：59

作者：

Voelker, Linus A. ^{[1
,2
]}

Kaufeld, Jessica ^{[3
]}

Miesbach, Wolfgang ^{[4
,5
]}

Braehler, Sebastian ^{[1
,2
]}

Reinhardt, Martin ^{[3
]}

Kuehne, Lucas ^{[1
,2
]}

Muehlfeld, Anja ^{[6
]}

Schreiber, Adrian ^{[7
,8
]}

Gaedeke, Jens ^{[7
,8
]}

Toelle, Markus ^{[9
,10
,11
,12
]}

Jabs, Wolfram J. ^{[13
]}

Ozcan, Fedai ^{[14
]}

Markau, Silke ^{[15
]}

Girndt, Matthias ^{[15
]}

Bauer, Frederic ^{[16
]}

Westhoff, Timm H. ^{[16
]}

Felten, Helmut ^{[17
]}

Hausberg, Martin ^{[17
]}

Brand, Marcus ^{[18
]}

Gerth, Jens ^{[19
]}

Bieringer, Markus ^{[20
]}

Bommer, Martin ^{[21
]}

Zschiedrich, Stefan ^{[22
]}

Schneider, Johanna ^{[22
]}

Elitok, Saban ^{[23
]}

Gawlik, Alexander ^{[23
]}

Gaeckler, Anja ^{[24
]}

Kribben, Andreas ^{[24
]}

Schwenger, Vedat ^{[25
]}

Schoenermarck, Ulf ^{[26
]}

Roeder, Maximilian ^{[27
]}

Radermacher, Joerg ^{[28
]}

Bramstedt, Joern ^{[29
]}

Morgner, Anke ^{[30
]}

Herbst, Regina ^{[30
]}

Harth, Ana ^{[31
]}

Potthoff, Sebastian A. ^{[30
,32
]}

von Auer, Charis ^{[33
]}

Wendt, Ralph ^{[34
]}

Christ, Hildegard ^{[35
]}

Brinkkoetter, Paul T. ^{[1
,2
]}

Menne, Jan ^{[3
]}

机构：

[1] Univ Cologne, Univ Hosp Cologne, Ctr Mol Med Cologne, Fac Med,Dept Internal Med 2, Cologne, Germany

[2] Cologne Cluster Excellence Cellular Stress Respon, Cologne, Germany

[3] Med Sch Hannover, Dept Nephrol & Hypertens, Carl Neuberg Str 1, D-30625 Hannover, Germany

[4] Univ Hosp Frankfurt, Dept Haemostaseol, Frankfurt, Germany

[5] Univ Hosp Frankfurt, Haemophilia Ctr, Frankfurt, Germany

[6] Uniklin RWTH Aachen, Div Nephrol & Clin Immunol, Aachen, Germany

[7] Charite, Dept Nephrol Intens Care Med, Berlin, Germany

[8] Helmholtz Assoc, Expt & Clin Res Ctr, Charite Max Delbruck Ctr Mol Med, Berlin, Germany

[9] Charite Univ Med Berlin, Berlin, Germany

[10] Free Univ Berlin, Berlin, Germany

[11] Humboldt Univ, Berlin, Germany

[12] Berlin Inst Hlth, Dept Nephrol & Intens Care Med, Berlin, Germany

[13] Vivantes Klinikum Friedrichshain, Dept Nephrol, Berlin, Germany

[14] Klinikum Dortmund, Dept Nephrol & Emergency Med, Dortmund, Germany

[15] Martin Luther Univ Halle Wittenberg, Dept Internal Med 2, Halle, Germany

[16] Ruhr Univ Bochum, Marien Hosp Herne, Med Dept 1, Bochum, Germany

[17] Karlsruhe Gen Hosp, Dept Gen Internal Med Nephrol Rheumatol & Pneumol, Karlsruhe, Germany

[18] Univ Munster, Dept Internal Med D, Munster, Germany

[19] Heinrich Braun Klinikum Zwickau, Dept Internal Med 2, Zwickau, Germany

[20] HELIOS Klin, Dept Cardiol & Nephrol, Berlin, Germany

[21] Alb Fils Kliniken, Dept Internal Med Hematol Oncol Palliat Care & In, Goppingen, Germany

[22] Univ Freiburg, Med Cetr, Fac Med, Dept Nephrol & Primary Care, Freiburg, Germany

[23] Klinikum Ernst von Bergmann, Dept Nephrol & Endocrinol Diabetol Potsdam, Potsdam, Germany

[24] Univ Essen Duisburg, Univ Hosp Essen, Dept Nephrol, Essen, Germany

[25] Klinikum Stuttgart, Dept Nephrol Hypertens & Autoimmune Disorders, Stuttgart, Germany

[26] Klinikum Univ Munchen, Nephrol Zentrum, Med Klin & Poliklin 4, Munich, Germany

[27] Klinikum Landshut, Sect Nephrol, Med Clin 1, Landshut, Germany

[28] Ruhr Univ Bochum, Ctr Internal Med Nephrol, Johannes Wesling Klinikum Minden, Minden, Germany

[29] Clin Cardiol Nephrol & Intens Care, Bremerhaven, Germany

[30] Klinikum Chemnitz GmbH, Dept Internal Med 3, Chemnitz, Germany

[31] Univ Witten Herdecke, Med Ctr Cologne Merheim, Dept Nephrol Transplantat & Med Intens Care, Cologne, Germany

[32] Heinrich Heine Univ, Med Fac, Dept Nephrol, Dusseldorf, Germany

[33] Johannes Gutenberg Univ Mainz, Dept Hematol Oncol & Pneumol, Univ Med Ctr, Mainz, Rheinland Pfalz, Germany

[34] Hosp St Georg, Dept Nephrol & Kuratorium Dialysis, Transplantat Renal Unit, Leipzig, Germany

[35] Univ Hosp Cologne, Inst Med Stat & Computat Biol, Cologne, Germany

来源：

BLOOD ADVANCES | 2020年 / 4卷 / 13期

关键词：

THROMBOTIC THROMBOCYTOPENIC PURPURA; PLASMA-EXCHANGE; RITUXIMAB; EFFICACY; SAFETY;

D O I：

10.1182/bloodadvances.2020001987

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：3093 / 3101

页数：9

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