• Flora Peyvandi, Marie Scully, Johanna A Kremer Hovinga, Spero Cataland, Paul Knöbl, Haifeng Wu, Andrea Artoni, John-Paul Westwood, Magnus Mansouri Taleghani, Bernd Jilma, Filip Callewaert, Hans Ulrichts, Christian Duby, Dominique Tersago, and TITAN Investigators.
• From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (F.P., A.A.), and the Department of Pathophysiology and Transplantation, University of Milan (F.P.) - both in Milan, Italy; the Department of Haematology, University College London Hospital (M.S., J.-P.W.), and the National Institute for Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London (M.S.) - both in London, U.K.; the University Clinic of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital and the University of Bern - both in Bern, Switzerland (J.A.K.H., M.M.T.); the Departments of Internal Medicine (S.C.) and Pathology (H.W.), Ohio State University, Columbus; the Departments of Medicine, Division of Hematology and Hemostasis (P.K.), and Clinical Pharmacology (B.J.), Medical University of Vienna, Vienna, Austria; and the Departments of Clinical Development (F.C., C.D., D.T.) and Pharmacology (H.U.), Ablynx, Zwijnaarde, Belgium.
• N. Engl. J. Med. 2016 Feb 11; 374 (6): 511-22.

BackgroundAcquired 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.MethodsCaplacizumab, 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.ResultsSeventy-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.ConclusionsCaplacizumab 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.).

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