title: Rituximab as pre-emptive treatment in patients with thrombotic thrombocytopenic purpura and evidence of anti-ADAMTS13 autoantibodies.
abstract: Thrombotic thrombocytopenic purpura (TTP) is a rare and severe disease characterized by thrombocytopenia, microangiopathic haemolytic anemia, neurological and renal involvement associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. Persistence of high titers of anti-ADAMTS13 autoantibodies predisposes to relapsing TTP. Since relapses are associated with high morbidity and mortality rates, the optimal therapeutic option should be a pre-emptive treatment able to deplete anti-ADAMTS13 autoantibodies and avoid relapses. Five patients who presented with persistence of undetectable ADAMTS13 activity and high titers of autoantibodies, were treated with rituximab as pre-emptive therapy during remission. Four of them were affected by relapsing TTP and one was treated after the first episode. ADAMTS13 activity ranging from 15% to 75% with disappearance of inhibitors was achieved after three months in all patients, and persisted >20% without inhibitors at six months. In three patients disease-free status is still ongoing after 29, 24 and six months, respectively. Relapses were documented in two patients during follow-up: in one patient remission lasted 51 months; while in the other patient relapse occurred after 13 months. Results demonstrated that rituximab used as pre-emptive treatment may be effective in maintaining a sustained remission in patients with anti-ADAMTS13 antibodies in whom other treatments failed to limit the production of inhibitors, and suggests that re-treatment with rituximab should be considered when ADAMTS13 activity decreases and inhibitors reappear into the circulation, to avoid a new relapse.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases Aldo e Cele Daccò, 24020 Ranica, Bergamo, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bresin
authors.forename: Sara
authors.initials: S
authors.lastname: Gastoldi
authors.forename: Erica
authors.initials: E
authors.lastname: Daina
authors.forename: Daniela
authors.initials: D
authors.lastname: Belotti
authors.forename: Enrico
authors.initials: E
authors.lastname: Pogliani
authors.forename: Paolo
authors.initials: P
authors.lastname: Perseghin
authors.forename: Potito R
authors.initials: PR
authors.lastname: Scalzulli
authors.forename: Rossella
authors.initials: R
authors.lastname: Paolini
authors.forename: Raimondo
authors.initials: R
authors.lastname: Marcenò
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Miriam
authors.initials: M
authors.lastname: Galbusera
mesh_terms: D051722:ADAM Proteins / Q000276:immunology*; D000071120:ADAMTS13 Protein; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011697:Purpura, Thrombotic Thrombocytopenic / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D012008:Recurrence; D012042:Registries; D012074:Remission Induction; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D007155:Immunologic Factors; D000069283:Rituximab; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human