title: Rituximab for treatment of inhibitors in haemophilia A. A Phase II study.
abstract: The development of antibodies against infused factor VIII (FVIII) in patients with haemophilia A is a serious complication leading to poorly controlled bleeding and increased morbidity. No treatment has been proven to reduce high titre antibodies in patients who fail immune tolerance induction or are not candidates for it. The Rituximab for the Treatment of Inhibitors in Congenital Hemophilia A (RICH) study was a phase II trial to assess whether rituximab can reduce anamnestic FVIII antibody (inhibitor) titres. Male subjects with severe congenital haemophilia A and an inhibitor titre ≥5 Bethesda Units/ml (BU) following a FVIII challenge infusion received rituximab 375 mg/m² weekly for weeks 1 through 4. Post-rituximab inhibitor titres were measured monthly from week 6 through week 22 to assess treatment response. Of 16 subjects who received at least one dose of rituximab, three (18.8%) met the criteria for a major response, defined as a fall in inhibitor titre to <5 BU, persisting after FVIII re-challenge. One subject had a minor response, defined as a fall in inhibitor titre to <5 BU, increasing to 5-10 BU after FVIII re-challenge, but <50% of the original peak inhibitor titre. Rituximab is useful in lowering inhibitor levels in patients, but its effect as a solo treatment strategy is modest. Future studies are indicated to determine the role of rituximab as an adjunctive therapy in immune tolerisation strategies.
authors.forename: C
authors.initials: C
authors.lastname: Leissinger
authors.forename: C D
authors.initials: CD
authors.lastname: Josephson
authors.affiliation: Suzanne Granger, MS, New England Research Institutes, Inc., 480 Pleasant St., Watertown, MA 02472, USA, Tel.: +1 617 972 3319, Fax: +1 617 926 8246, E-mail: SGranger@neriscience.com.
authors.forename: S
authors.initials: S
authors.lastname: Granger
authors.forename: B A
authors.initials: BA
authors.lastname: Konkle
authors.forename: R
authors.initials: R
authors.lastname: Kruse-Jarres
authors.forename: M V
authors.initials: MV
authors.lastname: Ragni
authors.forename: J M
authors.initials: JM
authors.lastname: Journeycake
authors.forename: L
authors.initials: L
authors.lastname: Valentino
authors.forename: N S
authors.initials: NS
authors.lastname: Key
authors.forename: J C
authors.initials: JC
authors.lastname: Gill
authors.forename: K R
authors.initials: KR
authors.lastname: McCrae
authors.forename: E J
authors.initials: EJ
authors.lastname: Neufeld
authors.forename: C
authors.initials: C
authors.lastname: Manno
authors.forename: L
authors.initials: L
authors.lastname: Raffini
authors.forename: K
authors.initials: K
authors.lastname: Saxena
authors.forename: M
authors.initials: M
authors.lastname: Torres
authors.forename: V
authors.initials: V
authors.lastname: Marder
authors.forename: C M
authors.initials: CM
authors.lastname: Bennett
authors.forename: S F
authors.initials: SF
authors.lastname: Assmann
mesh_terms: D000293:Adolescent; D000328:Adult; D019138:Antibodies, Blocking / Q000378:metabolism; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D000917:Antibody Formation / Q000187:drug effects; D018951:Antigens, CD20 / Q000276:immunology; D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000008:administration & dosage / Q000276:immunology; D005500:Follow-Up Studies; D006467:Hemophilia A / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D000069283:Rituximab; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D019138:Antibodies, Blocking; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007166:Immunosuppressive Agents; D000069283:Rituximab; D005169:Factor VIII
keywords: Anti-CD20; CD20 antibody; antibodies; blood coagulation inhibitor; haemophilia A; monoclonal; murine-derived