title: Remission in acute refractory and relapsing thrombotic thrombocytopenic purpura following rituximab is associated with a reduction in IgG antibodies to ADAMTS-13.
abstract: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder and plasma exchange (PEX) remains the primary treatment modality. Twenty-five patients with acute refractory/relapsing idiopathic TTP received rituximab in conjunction with PEX because of progressive clinical disease or deterioration in laboratory parameters, despite intensive standard therapy. In relapsing TTP, rituximab was started if antibody to ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin motif-13) was demonstrated during previous episodes. All 25 patients attained complete clinical and laboratory remission in a median of 11 d after initiating rituximab. In 21 cases, ADAMTS-13 activity was within the normal range following rituximab. Inhibitors were detected in 24/25 patients by mixing studies and/or immunoglobulin G (IgG) antibodies to ADAMTS-13 pre-rituximab. There was no evidence of inhibitors and/or IgG activity <10% in 23/25 patients following rituximab. In acute refractory cases, the median number of PEX pre-rituximab and following the first rituximab infusion was 13 and 9, respectively. There have been no infectious complications, despite low CD 19 levels and no relapses. In patients with acute refractory/relapsing idiopathic TTP, rituximab appears to be a safe, effective, targeted therapy with a significant reduction in the requirement for PEX.
authors.affiliation: Department of Haematology, University College London, London, UK. m.scully@ucl.ac.uk
authors.forename: Marie
authors.initials: M
authors.lastname: Scully
authors.forename: Hannah
authors.initials: H
authors.lastname: Cohen
authors.forename: Jamie
authors.initials: J
authors.lastname: Cavenagh
authors.forename: Sylvia
authors.initials: S
authors.lastname: Benjamin
authors.forename: Richard
authors.initials: R
authors.lastname: Starke
authors.forename: Sally
authors.initials: S
authors.lastname: Killick
authors.forename: Ian
authors.initials: I
authors.lastname: Mackie
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Machin
mesh_terms: D051722:ADAM Proteins / Q000276:immunology*; D000071120:ADAMTS13 Protein; D000208:Acute Disease; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19 / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010951:Plasma Exchange; D011697:Purpura, Thrombotic Thrombocytopenic / Q000276:immunology / Q000628:therapy*; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000069283:Rituximab; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human