Rituximab in the treatment of acquired factor VIII inhibitors.
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.
Wiestner
Adrian
A
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Cho
Hearn J
HJ
Asch
Adam S
AS
Michelis
Mary Ann
MA
Zeller
Jack A
JA
Peerschke
Ellinor I B
EI
Weksler
Babette B
BB
Schechter
Geraldine P
GP
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
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