title: Rituximab in the treatment of acquired factor VIII inhibitors.
abstract: Autoantibodies against factor VIII (FVIII) are rare but can cause life-threatening bleeding requiring costly factor replacement and prolonged immunosuppression. We report 4 consecutively treated patients whose acquired FVIII inhibitors responded rapidly to immunosuppressive regimens that included rituximab, a monoclonal antibody against CD20(+) B cells. Three patients had spontaneously occurring inhibitors. The fourth, a patient with mild hemophilia A, developed both an autoantibody and an alloantibody following recombinant FVIII treatment. Pretreatment FVIII activities ranged from less than 1% to 4% and inhibitor titers from 5 to 60 Bethesda units (BU). One patient with polymyalgia rheumatica who developed the inhibitor while receiving prednisone responded to single agent rituximab. The hemophilia patient had rapid resolution of the autoantibody, whereas the alloantibody persisted for months. Responses continue off treatment from more than 7 to more than 12 months. This report adds to the growing evidence that rituximab has efficacy in immune disorders resulting from autoantibody formation.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Wiestner
authors.forename: Hearn J
authors.initials: HJ
authors.lastname: Cho
authors.forename: Adam S
authors.initials: AS
authors.lastname: Asch
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Michelis
authors.forename: Jack A
authors.initials: JA
authors.lastname: Zeller
authors.forename: Ellinor I B
authors.initials: EI
authors.lastname: Peerschke
authors.forename: Babette B
authors.initials: BB
authors.lastname: Weksler
authors.forename: Geraldine P
authors.initials: GP
authors.lastname: Schechter
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology / Q000628:therapy*; D001402:B-Lymphocytes / Q000276:immunology; D005169:Factor VIII / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D006467:Hemophilia A / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007518:Isoantibodies / Q000096:biosynthesis / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000150:complications; D008206:Lymphatic Diseases / Q000150:complications; D008297:Male; D011111:Polymyalgia Rheumatica / Q000150:complications / Q000188:drug therapy; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D001323:Autoantibodies; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D000069283:Rituximab; D005169:Factor VIII; D011241:Prednisone