Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura.

Peyvandi, Flora; Scully, Marie; Kremer Hovinga, Johanna Anna; Cataland, Spero; Knöbl, Paul; Wu, Haifeng; Artoni, Andrea; Westwood, John-Paul; Mansouri Taleghani, Magnus; Jilma, Bernd; Callewaert, Filip; Ulrichts, Hans; Duby, Christian; Tersago, Dominique (2016). Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura. New England journal of medicine NEJM, 374(6), pp. 511-522. Massachusetts Medical Society MMS 10.1056/NEJMoa1505533

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BACKGROUND Acquired thrombotic thrombocytopenic purpura (TTP) is caused by aggregation of platelets on ultralarge von Willebrand factor multimers. This microvascular thrombosis causes multiorgan ischemia with potentially life-threatening complications. Daily plasma exchange and immunosuppressive therapies induce remission, but mortality and morbidity due to microthrombosis remain high. METHODS Caplacizumab, an anti-von Willebrand factor humanized single-variable-domain immunoglobulin (Nanobody), inhibits the interaction between ultralarge von Willebrand factor multimers and platelets. In this phase 2, controlled study, we randomly assigned patients with acquired TTP to subcutaneous caplacizumab (10 mg daily) or placebo during plasma exchange and for 30 days afterward. The primary end point was the time to a response, defined as confirmed normalization of the platelet count. Major secondary end points included exacerbations and relapses. RESULTS Seventy-five patients underwent randomization (36 were assigned to receive caplacizumab, and 39 to receive placebo). The time to a response was significantly reduced with caplacizumab as compared with placebo (39% reduction in median time, P=0.005). Three patients in the caplacizumab group had an exacerbation, as compared with 11 patients in the placebo group. Eight patients in the caplacizumab group had a relapse in the first month after stopping the study drug, of whom 7 had ADAMTS13 activity that remained below 10%, suggesting unresolved autoimmune activity. Bleeding-related adverse events, most of which were mild to moderate in severity, were more common with caplacizumab than with placebo (54% of patients vs. 38%). The frequencies of other adverse events were similar in the two groups. Two patients in the placebo group died, as compared with none in the caplacizumab group. CONCLUSIONS Caplacizumab induced a faster resolution of the acute TTP episode than did placebo. The platelet-protective effect of caplacizumab was maintained during the treatment period. Caplacizumab was associated with an increased tendency toward bleeding, as compared with placebo. (Funded by Ablynx; ClinicalTrials.gov number, NCT01151423.).

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 and Mansouri Taleghani, Magnus

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0028-4793

Publisher:

Massachusetts Medical Society MMS

Language:

English

Submitter:

Verena Zwahlen

Date Deposited:

29 Mar 2016 10:02

Last Modified:

16 Jul 2018 15:13

Publisher DOI:

10.1056/NEJMoa1505533

PubMed ID:

26863353

BORIS DOI:

10.7892/boris.79315

URI:

https://boris.unibe.ch/id/eprint/79315

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