Rituximab for treatment of inhibitors in haemophilia A. A Phase II study. Thromb Haemost 2014 Sep 02;112(3):445-58
Date
06/13/2014Pubmed ID
24919980Pubmed Central ID
PMC5726888DOI
10.1160/TH14-01-0078Scopus ID
2-s2.0-84907270053 (requires institutional sign-in at Scopus site) 44 CitationsAbstract
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.
Author List
Leissinger C, Josephson CD, Granger S, Konkle BA, Kruse-Jarres R, Ragni MV, Journeycake JM, Valentino L, Key NS, Gill JC, McCrae KR, Neufeld EJ, Manno C, Raffini L, Saxena K, Torres M, Marder V, Bennett CM, Assmann SFMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Antibodies, Blocking
Antibodies, Monoclonal, Murine-Derived
Antibody Formation
Antigens, CD20
Blood Coagulation
Child
Child, Preschool
Factor VIII
Follow-Up Studies
Hemophilia A
Humans
Immunosuppressive Agents
Male
Rituximab
Treatment Outcome
United States
Young Adult
