title: Efficiency of curative and prophylactic treatment with rituximab in ADAMTS13-deficient thrombotic thrombocytopenic purpura: a study of 11 cases.
abstract: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that occurs mainly in young adults. Acquired cases are usually a result of antibodies directed against ADAMTS13 (a disintegrin-like and metalloprotease [reprolysin type] with thrombospondin type 1 motif 13), a protease that cleaves the von Willebrand factor multimers. Prognosis has been improved by plasma therapy, but some acute severe forms are refractory to this treatment and achieving a sustained remission is still a challenge in chronic relapsing forms. We therefore conducted a multicentric open-label prospective trial to test the efficacy of rituximab, an anti-B-cell monoclonal antibody, as a curative and prophylactic treatment in patients with TTP as a result of anti-ADAMTS13 antibodies. Six patients were included during an acute refractory TTP episode. Five patients with severe relapsing TTP and persistent anti-ADAMTS13 antibodies were prophylactically treated during remission. All patients received 4 weekly infusions of rituximab. The target of treatment was to restore a significant ADAMTS13 plasma activity (> 10%). Treatment with rituximab led to clinical remission in all cases of acute refractory TTP. In all patients, anti-ADAMTS13 antibodies disappeared, and a significant (18%-75%) plasma ADAMTS13 activity was detected following treatment. Tolerance of rituximab was good. Rituximab is a promising first-line immunosuppressive treatment in patients with acute refractory and severe relapsing TTP related to anti-ADAMTS13 antibodies.
authors.affiliation: Service de Néphrologie, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France. fadi.fakhouri@nck.ap-hop-paris.fr
authors.forename: Fadi
authors.initials: F
authors.lastname: Fakhouri
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vernant
authors.forename: Agnès
authors.initials: A
authors.lastname: Veyradier
authors.forename: Martine
authors.initials: M
authors.lastname: Wolf
authors.forename: Gilles
authors.initials: G
authors.lastname: Kaplanski
authors.forename: Raynald
authors.initials: R
authors.lastname: Binaut
authors.forename: Manfred
authors.initials: M
authors.lastname: Rieger
authors.forename: Friedrich
authors.initials: F
authors.lastname: Scheiflinger
authors.forename: Pascale
authors.initials: P
authors.lastname: Poullin
authors.forename: Benjamin
authors.initials: B
authors.lastname: Deroure
authors.forename: Richard
authors.initials: R
authors.lastname: Delarue
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesavre
authors.forename: Philippe
authors.initials: P
authors.lastname: Vanhille
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Grünfeld
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000208:Acute Disease; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies / Q000097:blood / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000172:deficiency* / Q000276:immunology; D008875:Middle Aged; D011292:Premedication; D011697:Purpura, Thrombotic Thrombocytopenic / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D000069283:Rituximab; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human