. 2020 Jul 14;4(13):3085-3092.

doi: 10.1182/bloodadvances.2020001973.

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

Linus A Völker^{1

2}, Jessica Kaufeld³, Wolfgang Miesbach⁴, Sebastian Brähler^{1

2}, Martin Reinhardt³, Lucas Kühne^{1

2}, Anja Mühlfeld⁵, Adrian Schreiber^{6

7}, Jens Gaedeke^{6

7}, Markus Tölle⁸, Wolfram J Jabs⁹, Fedai Özcan¹⁰, Silke Markau¹¹, Matthias Girndt¹¹, Frederic Bauer¹², Timm H Westhoff¹², Helmut Felten¹³, Martin Hausberg¹³, Marcus Brand¹⁴, Jens Gerth¹⁵, Markus Bieringer¹⁶, Martin Bommer¹⁷, Stefan Zschiedrich¹⁸, Johanna Schneider¹⁸, Saban Elitok¹⁸, Alexander Gawlik¹⁸, Anja Gäckler¹⁹, Andreas Kribben¹⁹, Vedat Schwenger²⁰, Ulf Schoenermarck²¹, Maximilian Roeder²², Jörg Radermacher²³, Jörn Bramstedt²⁴, Anke Morgner²⁵, Regina Herbst²⁵, Ana Harth²⁶, Sebastian A Potthoff²⁷, Charis von Auer²⁸, Ralph Wendt²⁹, Hildegard Christ³⁰, Paul T Brinkkoetter^{1

2}, Jan Menne³

Affiliations

¹ Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
² Cologne Cluster of Excellence on Cellular Stress Responses in Ageing-Associated Diseases, Cologne, Germany.
³ Department of Nephrology and Hypertension, Medical School Hannover, Hannover, Germany.
⁴ Department of Hemostaseology-Hemophilia Center, University Hospital Frankfurt, Frankfurt, Germany.
⁵ Renal Division, Department of Medicine, Transplant Center Aachen, University of Aachen, Aachen, Germany.
⁶ Department of Nephrology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁷ Experimental and Clinical Research Center, Charité, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
⁸ Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Department of Nephrology and Intensive Care Medicine, Berlin Institute of Health, Berlin, Germany.
⁹ Department of Nephrology, Vivantes Klinikum im Friedrichshain, Berlin, Germany.
¹⁰ Department of Nephrology and Emergency Medicine, Klinikum Dortmund, Dortmund, Germany.
¹¹ Department of Internal Medicine II, Martin Luther University Halle-Wittenberg, Halle, Germany.
¹² Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University of Bochum, Herne, Germany.
¹³ Department of General Internal Medicine, Nephrology, Rheumatology, and Pneumology, Karlsruhe General Hospital, Karlsruhe, Germany.
¹⁴ Department of Internal Medicine D, University of Münster, Muenster, Germany.
¹⁵ Department of Internal Medicine II, Heinrich Braun Klinikum Zwickau, Zwickau, Germany.
¹⁶ Department of Cardiology and Nephrology, Helios Klinik Berlin-Buch, Berlin, Germany.
¹⁷ Department of Internal Medicine, Hematology, Oncology, Palliative Care, and Infectious Diseases, Alb-Fils-Kliniken, Göppingen, Germany.
¹⁸ Department of Nephrology and Endocrinology/Diabetology Potsdam, Klinikum Ernst von Bergmann, Potsdam, Germany.
¹⁹ Department of Nephrology, University Hospital Essen, University Essen-Duisburg, Essen, Germany.
²⁰ Department of Nephrology, Hypertension and Autoimmune Disorders, Klinikum Stuttgart, Stuttgart, Germany.
²¹ Klinikum der Universität München-Medizinische Klinik und Poliklinik IV, Nephrologisches Zentrum, Munich, Germany.
²² Section of Nephrology, Medical Clinic I, Klinikum Landshut, Landshut, Germany.
²³ Center for Internal Medicine/Nephrology, Johannes Wesling Klinikum Minden, University Hospital of the Ruhr-University of Bochum, Herne, Germany.
²⁴ Clinic of Cardiology, Nephrology and Intensive Care, Bremerhaven, Germany.
²⁵ Department of Internal Medicine III, Klinikum Chemnitz GmbH, Chemnitz, Germany.
²⁶ Department of Nephrology, Transplantation, and Medical Intensive Care, University Witten/Herdecke, Medical Center Cologne-Merheim, Cologne, Germany.
²⁷ Department of Nephrology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
²⁸ Department of Hematology, Oncology, and Pneumology, University Medical Center of the Johannes Gutenberg University, Mainz, Rheinland-Pfalz, Germany.
²⁹ Department of Nephrology and Kuratorium for Dialysis and Transplantation Renal Unit, Hospital St. Georg, Leipzig, Germany; and.
³⁰ Institute of Medical Statistics and Computational Biology, University Hospital of Cologne, Cologne, Germany.

PMID: 32634236
PMCID: PMC7362370
DOI: 10.1182/bloodadvances.2020001973

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

Linus A Völker et al. Blood Adv. 2020.

. 2020 Jul 14;4(13):3085-3092.

doi: 10.1182/bloodadvances.2020001973.

Authors

Affiliations

¹ Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
² Cologne Cluster of Excellence on Cellular Stress Responses in Ageing-Associated Diseases, Cologne, Germany.
³ Department of Nephrology and Hypertension, Medical School Hannover, Hannover, Germany.
⁴ Department of Hemostaseology-Hemophilia Center, University Hospital Frankfurt, Frankfurt, Germany.
⁵ Renal Division, Department of Medicine, Transplant Center Aachen, University of Aachen, Aachen, Germany.
⁶ Department of Nephrology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁷ Experimental and Clinical Research Center, Charité, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
⁸ Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Department of Nephrology and Intensive Care Medicine, Berlin Institute of Health, Berlin, Germany.
⁹ Department of Nephrology, Vivantes Klinikum im Friedrichshain, Berlin, Germany.
¹⁰ Department of Nephrology and Emergency Medicine, Klinikum Dortmund, Dortmund, Germany.
¹¹ Department of Internal Medicine II, Martin Luther University Halle-Wittenberg, Halle, Germany.
¹² Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University of Bochum, Herne, Germany.
¹³ Department of General Internal Medicine, Nephrology, Rheumatology, and Pneumology, Karlsruhe General Hospital, Karlsruhe, Germany.
¹⁴ Department of Internal Medicine D, University of Münster, Muenster, Germany.
¹⁵ Department of Internal Medicine II, Heinrich Braun Klinikum Zwickau, Zwickau, Germany.
¹⁶ Department of Cardiology and Nephrology, Helios Klinik Berlin-Buch, Berlin, Germany.
¹⁷ Department of Internal Medicine, Hematology, Oncology, Palliative Care, and Infectious Diseases, Alb-Fils-Kliniken, Göppingen, Germany.
¹⁸ Department of Nephrology and Endocrinology/Diabetology Potsdam, Klinikum Ernst von Bergmann, Potsdam, Germany.
¹⁹ Department of Nephrology, University Hospital Essen, University Essen-Duisburg, Essen, Germany.
²⁰ Department of Nephrology, Hypertension and Autoimmune Disorders, Klinikum Stuttgart, Stuttgart, Germany.
²¹ Klinikum der Universität München-Medizinische Klinik und Poliklinik IV, Nephrologisches Zentrum, Munich, Germany.
²² Section of Nephrology, Medical Clinic I, Klinikum Landshut, Landshut, Germany.
²³ Center for Internal Medicine/Nephrology, Johannes Wesling Klinikum Minden, University Hospital of the Ruhr-University of Bochum, Herne, Germany.
²⁴ Clinic of Cardiology, Nephrology and Intensive Care, Bremerhaven, Germany.
²⁵ Department of Internal Medicine III, Klinikum Chemnitz GmbH, Chemnitz, Germany.
²⁶ Department of Nephrology, Transplantation, and Medical Intensive Care, University Witten/Herdecke, Medical Center Cologne-Merheim, Cologne, Germany.
²⁷ Department of Nephrology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
²⁸ Department of Hematology, Oncology, and Pneumology, University Medical Center of the Johannes Gutenberg University, Mainz, Rheinland-Pfalz, Germany.
²⁹ Department of Nephrology and Kuratorium for Dialysis and Transplantation Renal Unit, Hospital St. Georg, Leipzig, Germany; and.
³⁰ Institute of Medical Statistics and Computational Biology, University Hospital of Cologne, Cologne, Germany.

PMID: 32634236
PMCID: PMC7362370
DOI: 10.1182/bloodadvances.2020001973

Erratum in

Völker LA, Kaufeld J, Miesbach W, et al. Real-world data confirm the effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura. Blood Adv. 2020;4(13):3085-3092.
[No authors listed] [No authors listed] Blood Adv. 2022 Apr 12;6(7):2434. doi: 10.1182/bloodadvances.2021006915. Blood Adv. 2022. PMID: 35404433 Free PMC article. No abstract available.

Abstract

Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare but life-threatening condition. In 2018, the nanobody caplacizumab was approved for the treatment of adults experiencing an acute episode of aTTP, in conjunction with plasma exchange (PEX) and immunosuppression for a minimum of 30 days after stopping daily PEX. We performed a retrospective, observational analysis on the use of caplacizumab in 60 patients from 29 medical centers in Germany during acute disease management. Caplacizumab led to a rapid normalization of the platelet count (median, 3 days; mean 3.78 days). One patient died after late treatment initiation due to aTTP-associated complications. In 2 patients with initial disease presentation and in 4 additional patients with laboratory signs of an exacerbation or relapse after the initial therapy, PEX-free treatment regimens could be established with overall favorable outcome. Caplacizumab is efficacious in the treatment of aTTP independent of timing and ancillary treatment modalities. Based on this real-world experience and published literature, we propose to administer caplacizumab immediately to all patients with an acute episode of aTTP. Treatment decisions regarding the use of PEX should be based on the severity of the clinical presentation and known risk factors. PEX might be dispensable in some patients.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: P.T.B. reports grants from the German Research Foundation (BR2955/8) during the conduct of the study and personal fees from Alexion, Astellas, Bayer, Sanofi Genzyme, Pfizer, and Vifor (speaker honoraria, advisory boards). L.A.V. reports grants from the Else-Kroener-Fresenius Stiftung (2015_A224) and speaker honoraria from Sanofi-Genzyme. S.B. receives grant support from the German Research Foundation (BR4917/3). J.M. received personal fees from Alexion, Sanofi Genzyme, and Ablynx (speaker honoraria, advisory boards). S.P. received personal fees from Alexion, Sanofi Genzyme, and Ablynx (speaker honoraria, advisory boards). R.W. received personal fees from Alexion, Sanofi Genzyme, and Ablynx (speaker honoraria, advisory boards, educational materials and review writing). W.J.J. received speaker honoraria from Alexion and Ablynx (advisory boards). W.M. received honoraria from Ablynx, Takeda, and Shire (speaker honoraria, advisory boards). M.T. reports research grants from the Sonnenfeld Stiftung, Charité3R, and Novartis and personal fees from Baxter, Cytosorbents, Novartis, and Takeda (speaker honoraria, advisory boards). M.R. reports personal fees from Alexion, Diamed, Roche, and Sanofi Genzyme (speaker honoraria, travel support). A. Gäckler reports personal fees from Alexion and Ablynx (speaker honoraria, advisory boards). F.B. received honoraria from Amgen, Sanofi, Akcea, Hexal, MSD, AstraZeneca, Alexion, and Astellas (speaker honoraria, advisory boards). U.S. reports study fees, travel support and consultancy fees from Alexion and study fees and consultancy fees Ablynx. M. Bommer has received honoraria from Ablynx, Alexion, Sanofi, and Amgen, as well as study fees from Ablynx and Amgen. C.v.A. reports personal fees from Sanofi Genzyme (advisory boards). The remaining authors declare no competing financial interests.

Figures

**Figure 1.**
**Violin blots depict the distribution of main treatment and outcome parameters.** Red lines indicate medians; blue lines indicate 75th and 25th interpercentile quartile. ^aTotal stay includes before, during, and after caplacizumab treatment.

**Figure 2.**
**Average platelet counts and standard error of the mean in relation to the start of caplacizumab treatment.** Average platelet counts (A) and lactate dehydrogenase (B) and standard error of the mean in relation to the start of caplacizumab treatment. The x-axis (time in days) denotes the time elapsed since the start of caplacizumab and not since the initial diagnosis (ie, day 0). Please note that there is no fixed correlation between the beginning of caplacizumab and the beginning of the treatment, because caplacizumab was not used as a frontline agent in a relevant number of instances. Green dotted lines indicate upper limit of normal (ULN) or lower limit of normal (LLN).

**Figure 3.**
**Kaplan-Meier curves of patient fractions remaining without final normalization of platelet count (>150 × 10**⁹**/L) after the start of caplacizumab treatment.**

See this image and copyright information in PMC

References

1. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836-2846. - PubMed
1. Miesbach W, Menne J, Bommer M, et al. . Incidence of acquired thrombotic thrombocytopenic purpura in Germany: a hospital level study. Orphanet J Rare Dis. 2019;14(1):260. - PMC - PubMed
1. Peyvandi F, Scully M, Kremer Hovinga JA, et al. ; TITAN Investigators . Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016;374(6):511-522. - PubMed
1. Scully M, Cataland SR, Peyvandi F, et al. ; HERCULES Investigators . Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346. - PubMed
1. Bendapudi PK, Hurwitz S, Fry A, et al. . Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol. 2017;4(4):e157-e164. - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Medical
- ClinicalTrials.gov

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical