Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura.

Scully, Marie; Cataland, Spero R; Peyvandi, Flora; Coppo, Paul; Knöbl, Paul; Kremer Hovinga, Johanna A.; Metjian, Ara; de la Rubia, Javier; Pavenski, Katerina; Callewaert, Filip; Biswas, Debjit; De Winter, Hilde; Zeldin, Robert K (2019). Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura. The New England journal of medicine, 380(4), pp. 335-346. Massachusetts Medical Society 10.1056/NEJMoa1806311

[img] Text
Caplacizumab.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (420kB) | Request a copy

BACKGROUND In acquired thrombotic thrombocytopenic purpura (TTP), an immune-mediated deficiency of the von Willebrand factor-cleaving protease ADAMTS13 allows unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis, which result in thrombocytopenia, hemolytic anemia, and tissue ischemia. Caplacizumab, an anti-von Willebrand factor humanized, bivalent variable-domain-only immunoglobulin fragment, inhibits interaction between von Willebrand factor multimers and platelets. METHODS In this double-blind, controlled trial, we randomly assigned 145 patients with TTP to receive caplacizumab (10-mg intravenous loading bolus, followed by 10 mg daily subcutaneously) or placebo during plasma exchange and for 30 days thereafter. The primary outcome was the time to normalization of the platelet count, with discontinuation of daily plasma exchange within 5 days thereafter. Key secondary outcomes included a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the trial treatment period; recurrence of TTP at any time during the trial; refractory TTP; and normalization of organ-damage markers. RESULTS The median time to normalization of the platelet count was shorter with caplacizumab than with placebo (2.69 days [95% confidence interval {CI}, 1.89 to 2.83] vs. 2.88 days [95% CI, 2.68 to 3.56], P=0.01), and patients who received caplacizumab were 1.55 times as likely to have a normalization of the platelet count as those who received placebo. The percentage of patients with a composite outcome event was 74% lower with caplacizumab than with placebo (12% vs. 49%, P<0.001). The percentage of patients who had a recurrence of TTP at any time during the trial was 67% lower with caplacizumab than with placebo (12% vs. 38%, P<0.001). Refractory disease developed in no patients in the caplacizumab group and in three patients in the placebo group. Patients who received caplacizumab needed less plasma exchange and had a shorter hospitalization than those who received placebo. The most common adverse event was mucocutaneous bleeding, which was reported in 65% of the patients in the caplacizumab group and in 48% in the placebo group. During the trial treatment period, three patients in the placebo group died. One patient in the caplacizumab group died from cerebral ischemia after the end of the treatment period. CONCLUSIONS Among patients with TTP, treatment with caplacizumab was associated with faster normalization of the platelet count; a lower incidence of a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the treatment period; and a lower rate of recurrence of TTP during the trial than placebo. (Funded by Ablynx; HERCULES ClinicalTrials.gov number, NCT02553317 .).

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)

UniBE Contributor:

Kremer Hovinga, Johanna Anna

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1533-4406

Publisher:

Massachusetts Medical Society

Language:

English

Submitter:

Pierrette Durand Lüthi

Date Deposited:

17 Sep 2019 08:46

Last Modified:

22 Oct 2019 19:37

Publisher DOI:

10.1056/NEJMoa1806311

PubMed ID:

30625070

BORIS DOI:

10.7892/boris.133187

URI:

https://boris.unibe.ch/id/eprint/133187

Actions (login required)

Edit item Edit item
Provide Feedback