Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2).
OBJECTIVE
Increased concentrations of tumor necrosis factor (TNF), a potent proinflammatory cytokine, can be shown in the mucosa of patients with active Crohn's disease. Neutralization of TNF has been shown to decrease recruitment of inflammatory cells and granuloma formation in several animal models. The aim of this study was to investigate the safety and potential efficacy of an anti-TNF monoclonal antibody in the treatment of active Crohn's disease.


METHODS
Ten patients with active Crohn's disease that was unresponsive to therapy were administered a single infusion of an anti-TNF human/mouse chimeric monoclonal antibody (cA2) in an open-label treatment protocol while the baseline anti-inflammatory therapy was continued.


RESULTS
Eight patients showed normalization of Crohn's Disease Activity Index scores and healing of ulcerations as judged by colonoscopy within 4 weeks after treatment. One patient had a perforation after colonoscopy and recovered completely after surgery. One elderly patient showed a poor response. The average duration of response after a single infusion was 4 months. No adverse experiences related to cA2 were observed.


CONCLUSIONS
The results support the hypothesis that TNF is of major importance in the pathogenesis of Crohn's disease. Treatment with cA2 was safe and may be useful in patients with Crohn's disease that is unresponsive to steroid treatment.
van Dullemen
H M
HM
Department of Hepatogastroenterology, Academic Medical Center, Amsterdam, The Netherlands.
van Deventer
S J
SJ
Hommes
D W
DW
Bijl
H A
HA
Jansen
J
J
Tytgat
G N
GN
Woody
J
J
D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D003001:Cloning, Molecular; D003106:Colon / Q000473:pathology; D003424:Crohn Disease / Q000097:blood / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D000069285:Infliximab; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012008:Recurrence; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000069285:Infliximab