PMID- 17206633
OWN - NLM
STAT- MEDLINE
DCOM- 20070322
LR  - 20220318
IS  - 1078-0998 (Print)
IS  - 1078-0998 (Linking)
VI  - 13
IP  - 1
DP  - 2007 Jan
TI  - Safety and tolerability of concurrent natalizumab treatment for patients with 
      Crohn's disease not in remission while receiving infliximab.
PG  - 2-11
AB  - BACKGROUND: Natalizumab, a humanized monoclonal IgG(4) antibody to alpha4 
      integrin, was investigated as a treatment of active Crohn's disease (CD). The 
      safety of natalizumab given in combination with infliximab has not previously 
      been studied. METHODS: Seventy-nine adult patients with active CD (Crohn's 
      Disease Activity Index [CDAI] score > or = 150) despite ongoing infliximab 
      treatment were randomized 2:1 to receive 3 intravenous infusions of natalizumab 
      (300 mg; n = 52) or placebo (n = 27) every 4 weeks. Patients received infliximab 
      (5 mg/kg) every 8 weeks for at least 10 weeks before randomization and throughout 
      the study. The primary objective was to assess the short-term safety and 
      tolerability of natalizumab in patients concurrently receiving infliximab. 
      Secondary and tertiary objectives included measures of efficacy, health-related 
      quality of life (HRQoL), and effects on inflammatory markers. A subset of 
      patients also participated in a pharmacokinetic/pharmacodynamic (PK/PD) analysis 
      of the effects of concurrent treatment. RESULTS: Incidence of adverse events 
      (AEs) was similar in the treatment groups. AEs frequently reported in both groups 
      were headache, CD exacerbation, nausea, and nasopharyngitis. No patient had a 
      hypersensitivity-like reaction to natalizumab, whereas 4 patients (5%) 
      experienced reactions to infliximab. Two patients (4%) developed anti-natalizumab 
      antibodies; 10 patients (14%) developed anti-infliximab antibodies. The mean CDAI 
      score decreased with natalizumab plus infliximab but was unchanged with 
      infliximab alone (-37.7 versus +3.5; P = 0.084). Patients in both groups showed 
      small increases in HRQoL (P = 0.811). No drug-drug interactions were noted. 
      CONCLUSIONS: The combination of natalizumab plus infliximab was well tolerated. 
      Several positive trends suggested that treating patients not in remission with 
      infliximab plus natalizumab had greater efficacy than treatment with infliximab 
      alone.
FAU - Sands, Bruce E
AU  - Sands BE
AD  - Gastrointestinal Unit, MGH Crohn's and Colitis Center, Massachusetts General 
      Hospital, Harvard Medical School, Boston, Massachusetts, USA. bsands@partners.org
FAU - Kozarek, Richard
AU  - Kozarek R
FAU - Spainhour, Jack
AU  - Spainhour J
FAU - Barish, Charles F
AU  - Barish CF
FAU - Becker, Scott
AU  - Becker S
FAU - Goldberg, Lawrence
AU  - Goldberg L
FAU - Katz, Seymour
AU  - Katz S
FAU - Goldblum, Ronald
AU  - Goldblum R
FAU - Harrigan, Rena
AU  - Harrigan R
FAU - Hilton, Deborah
AU  - Hilton D
FAU - Hanauer, Stephen B
AU  - Hanauer SB
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - England
TA  - Inflamm Bowel Dis
JT  - Inflammatory bowel diseases
JID - 9508162
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Gastrointestinal Agents)
RN  - 0 (Natalizumab)
RN  - 0 (Serum Albumin)
RN  - 143198-26-9 (Integrin alpha4)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - B72HH48FLU (Infliximab)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal/*administration & dosage/adverse effects/pharmacokinetics
MH  - Antibodies, Monoclonal, Humanized
MH  - C-Reactive Protein/analysis
MH  - Crohn Disease/blood/*drug therapy
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Gastrointestinal Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Humans
MH  - Infliximab
MH  - Integrin alpha4/immunology
MH  - Male
MH  - Natalizumab
MH  - Quality of Life
MH  - Serum Albumin/analysis
EDAT- 2007/01/09 09:00
MHDA- 2007/03/23 09:00
CRDT- 2007/01/09 09:00
PHST- 2007/01/09 09:00 [pubmed]
PHST- 2007/03/23 09:00 [medline]
PHST- 2007/01/09 09:00 [entrez]
AID - 10.1002/ibd.20014 [doi]
PST - ppublish
SO  - Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014.