PMID- 19240707
OWN - NLM
STAT- MEDLINE
DCOM- 20090421
LR  - 20180228
IS  - 1572-0241 (Electronic)
IS  - 0002-9270 (Linking)
VI  - 104
IP  - 4
DP  - 2009 Apr
TI  - Transient cytokine-induced liver injury following administration of the humanized 
      anti-CD3 antibody visilizumab (HuM291) in Crohn's disease.
PG  - 868-76
LID - 10.1038/ajg.2008.138 [doi]
AB  - OBJECTIVES: Monoclonal antibodies to CD3 and CD4 T-cell receptors are evolving 
      for Crohn's disease (CD) and ulcerative colitis. Their administration is often 
      associated with a cytokine release syndrome (CRS). METHODS: We evaluated data 
      from two prospective clinical trials (NCT00267709 and NCT00267722) of visilizumab 
      (HuM291), a novel humanized anti-CD3 antibody, in 34 patients with CD who 
      received 10 microg/kg intravenously on 2 consecutive days. Serum hepatic tests 
      including bilirubin, alkaline phosphatase (AP), gamma-glutamyltransferase (GGT), 
      alanine aminotransferase (ALT) and aspartate aminotransferase (AST), visilizumab 
      concentrations, and a panel of 16 cytokines were measured pre- and 
      postadministration of visilizumab. RESULTS: Patients experienced CRS symptoms at 
      a median of 45 min postinfusion. The cytokine profile was characterized by 
      interferon-inducible protein-10 (IP-10), interleukin-10 (IL-10), tumor necrosis 
      factor-alpha (TNF-alpha), interferon-gamma, monocyte chemotactic protein 1 
      (MCP-1), interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-2 (IL-2), and 
      interleukin 1 receptor antagonist (IL-1Ra), which were elevated between 6 
      (IL-1Ra) and 870 (IP-10) times their baseline concentrations. TNF-alpha and IL-2 
      peaked at the first day 1 h post infusion, whereas all others peaked at 6 h post 
      infusion. Eighty-six percent of patients experienced an elevation above the upper 
      limit of normal in hepatic enzymes (GGT 73%, AST 73%, ALT 64%, and AP 42% of 
      patients), but not bilirubin, within 6 h postinfusion. CONCLUSIONS: Transient 
      elevation of hepatic enzymes occurred frequently in patients with CD treated with 
      visilizumab and was associated with CRS. CD patients could be predisposed due to 
      an aberrant expression of adhesion molecules in the liver that promotes CRS upon 
      engagement of the T-cell receptor and may relate to extraintestinal disease 
      manifestations such as primary sclerosing cholangitis.
FAU - Baumgart, Daniel C
AU  - Baumgart DC
AD  - Division of Gastroenterology and Hepatology, Department of Medicine, Charite 
      Medical School, Humboldt University of Berlin, Berlin, Germany. 
      daniel.baumgart@charite.de
FAU - Lowder, James N
AU  - Lowder JN
FAU - Targan, Stephan R
AU  - Targan SR
FAU - Sandborn, William J
AU  - Sandborn WJ
FAU - Frankel, Matthew B
AU  - Frankel MB
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20090224
PL  - United States
TA  - Am J Gastroenterol
JT  - The American journal of gastroenterology
JID - 0421030
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (CD3 Complex)
RN  - 0 (Cytokines)
RN  - EC 2.3.2.2 (gamma-Glutamyltransferase)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
RN  - H18SKU3289 (visilizumab)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Alanine Transaminase/blood
MH  - Alkaline Phosphatase/blood
MH  - Antibodies, Monoclonal/administration & dosage/*adverse effects/pharmacokinetics
MH  - Antibodies, Monoclonal, Humanized
MH  - Aspartate Aminotransferases/blood
MH  - Bilirubin/blood
MH  - CD3 Complex/immunology
MH  - *Chemical and Drug Induced Liver Injury
MH  - Crohn Disease/blood/*drug therapy
MH  - Cytokines/blood
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Injections, Intravenous
MH  - Liver Diseases/blood
MH  - Liver Function Tests
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Young Adult
MH  - gamma-Glutamyltransferase/blood
EDAT- 2009/02/26 09:00
MHDA- 2009/04/22 09:00
CRDT- 2009/02/26 09:00
PHST- 2009/02/26 09:00 [entrez]
PHST- 2009/02/26 09:00 [pubmed]
PHST- 2009/04/22 09:00 [medline]
AID - ajg2008138 [pii]
AID - 10.1038/ajg.2008.138 [doi]
PST - ppublish
SO  - Am J Gastroenterol. 2009 Apr;104(4):868-76. doi: 10.1038/ajg.2008.138. Epub 2009 
      Feb 24.