A randomized placebo-controlled trial of a humanized monoclonal antibody to alpha4 integrin in active Crohn's disease.
OBJECTIVE
alpha4 integrins are important mediators of leukocyte migration across vascular endothelium. This pilot placebo-controlled study aimed to assess the safety and efficacy of natalizumab, a recombinant humanized monoclonal antibody to alpha4 integrin, in patients with mild to moderately active Crohn's disease.


METHODS
Thirty patients with active Crohn's disease (Crohn's Disease Activity Index [CDAI] > or =151 and < or =450) received a 3-mg/kg infusion of natalizumab (n = 18) or placebo (n = 12) by double-blind randomization. The study's primary endpoint was change in CDAI at week 2.


RESULTS
At week 2, the CDAI decreased significantly from baseline after infusion of natalizumab (mean 45 points) but not placebo (mean 11 points). Seven (39%) natalizumab-treated patients achieved remission at week 2, compared with 1 (8%) treated with placebo. In contrast, 4 (33%) of the placebo-treated patients required rescue medication by week 2, compared with 2 (11%) natalizumab-treated patients. Significant increases in circulating B and T lymphocytes were detected only after natalizumab administration. The frequency of commonly reported adverse events did not differ significantly between groups.


CONCLUSIONS
A single 3-mg/kg natalizumab infusion was well tolerated by Crohn's disease patients, although the dose used may have been suboptimal. Elevated circulating lymphocyte levels after natalizumab suggest interrupted lymphocyte trafficking. Natalizumab therapy in active Crohn's disease merits further investigation.
Gordon
F H
FH
Centre for Gastroenterology, Department of Medicine, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, England. fionagordon@ownhomeline.freeserve.co.uk
Lai
C W
CW
Hamilton
M I
MI
Allison
M C
MC
Srivastava
E D
ED
Fouweather
M G
MG
Donoghue
S
S
Greenlees
C
C
Subhani
J
J
Amlot
P L
PL
Pounder
R E
RE
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015703:Antigens, CD / Q000276:immunology*; D015415:Biomarkers; D003424:Crohn Disease / Q000276:immunology / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D039441:Integrin alpha4; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015415:Biomarkers; D039441:Integrin alpha4