PMID- 24919980
OWN - NLM
STAT- MEDLINE
DCOM- 20150615
LR  - 20211021
IS  - 2567-689X (Electronic)
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 112
IP  - 3
DP  - 2014 Sep 2
TI  - Rituximab for treatment of inhibitors in haemophilia A. A Phase II study.
PG  - 445-58
LID - 10.1160/TH14-01-0078 [doi]
AB  - 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/m(2) 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.
FAU - Leissinger, C
AU  - Leissinger C
FAU - Josephson, C D
AU  - Josephson CD
FAU - Granger, S
AU  - Granger S
AD  - 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.
FAU - Konkle, B A
AU  - Konkle BA
FAU - Kruse-Jarres, R
AU  - Kruse-Jarres R
FAU - Ragni, M V
AU  - Ragni MV
FAU - Journeycake, J M
AU  - Journeycake JM
FAU - Valentino, L
AU  - Valentino L
FAU - Key, N S
AU  - Key NS
FAU - Gill, J C
AU  - Gill JC
FAU - McCrae, K R
AU  - McCrae KR
FAU - Neufeld, E J
AU  - Neufeld EJ
FAU - Manno, C
AU  - Manno C
FAU - Raffini, L
AU  - Raffini L
FAU - Saxena, K
AU  - Saxena K
FAU - Torres, M
AU  - Torres M
FAU - Marder, V
AU  - Marder V
FAU - Bennett, C M
AU  - Bennett CM
FAU - Assmann, S F
AU  - Assmann SF
LA  - eng
GR  - U01 HL072346/HL/NHLBI NIH HHS/United States
GR  - HL072290/HL/NHLBI NIH HHS/United States
GR  - HL072268/HL/NHLBI NIH HHS/United States
GR  - U01 HL072291/HL/NHLBI NIH HHS/United States
GR  - HL072331/HL/NHLBI NIH HHS/United States
GR  - HL072033/HL/NHLBI NIH HHS/United States
GR  - HL072283/HL/NHLBI NIH HHS/United States
GR  - HL072274/HL/NHLBI NIH HHS/United States
GR  - HL072248/HL/NHLBI NIH HHS/United States
GR  - U01 HL072283/HL/NHLBI NIH HHS/United States
GR  - U01 HL072274/HL/NHLBI NIH HHS/United States
GR  - U01 HL072355/HL/NHLBI NIH HHS/United States
GR  - U01 HL072248/HL/NHLBI NIH HHS/United States
GR  - U01 HL072268/HL/NHLBI NIH HHS/United States
GR  - U01 HL072290/HL/NHLBI NIH HHS/United States
GR  - HL072346/HL/NHLBI NIH HHS/United States
GR  - U01 HL072331/HL/NHLBI NIH HHS/United States
GR  - HL072291/HL/NHLBI NIH HHS/United States
GR  - HL072355/HL/NHLBI NIH HHS/United States
GR  - U01 HL072033/HL/NHLBI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
DEP - 20140612
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Antibodies, Monoclonal, Murine-Derived)
RN  - 0 (Antigens, CD20)
RN  - 0 (Immunosuppressive Agents)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 9001-27-8 (Factor VIII)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Blocking/metabolism
MH  - Antibodies, Monoclonal, Murine-Derived/*administration & dosage/adverse effects
MH  - Antibody Formation/drug effects
MH  - Antigens, CD20/immunology
MH  - Blood Coagulation/drug effects/genetics
MH  - Child
MH  - Child, Preschool
MH  - Factor VIII/administration & dosage/immunology
MH  - Follow-Up Studies
MH  - Hemophilia A/*drug therapy/genetics
MH  - Humans
MH  - Immunosuppressive Agents/*administration & dosage/adverse effects
MH  - Male
MH  - Rituximab
MH  - Treatment Outcome
MH  - United States
MH  - Young Adult
PMC - PMC5726888
MID - NIHMS924625
OTO - NOTNLM
OT  - Anti-CD20
OT  - CD20 antibody
OT  - antibodies
OT  - blood coagulation inhibitor
OT  - haemophilia A
OT  - monoclonal
OT  - murine-derived
COIS- Conflict of Interest C. Leissinger reports receiving grant funding from Baxter, 
      NovoNordisk and CSL Behring, and receiving honoraria for speaking and 
      participation in advisory boards for Baxter, Bayer, CSL Behring, Kedrion, 
      NovoNordisk, and Pfizer. J.C. Gill reports receiving honoraria for advisory board 
      membership for Baxter, Bayer, CSL Behring and Octapharma.
EDAT- 2014/06/13 06:00
MHDA- 2015/06/16 06:00
PMCR- 2017/12/12
CRDT- 2014/06/13 06:00
PHST- 2014/01/24 00:00 [received]
PHST- 2014/03/22 00:00 [accepted]
PHST- 2014/06/13 06:00 [entrez]
PHST- 2014/06/13 06:00 [pubmed]
PHST- 2015/06/16 06:00 [medline]
PHST- 2017/12/12 00:00 [pmc-release]
AID - 14-01-0078 [pii]
AID - 10.1160/TH14-01-0078 [doi]
PST - ppublish
SO  - Thromb Haemost. 2014 Sep 2;112(3):445-58. doi: 10.1160/TH14-01-0078. Epub 2014 
      Jun 12.