Wj. Sandborn et Sb. Hanauer, Antitumor necrosis factor therapy for inflammatory bowel disease: A reviewof agents, pharmacology, clinical results, and safety, INFLAMM B D, 5(2), 1999, pp. 119-133
Tumor necrosis factor-alpha (TNF alpha), a proinflammatory cytokine, plays
an important role in the pathogenesis of inflammatory bowel disease (IBD).
Biotechnology agents including a chimeric monoclonal anti-TNF antibody (inf
liximab), a humanized monoclonal anti-TNF antibody (CDP571), and a recombin
ant TNF receptor fusion protein (etanercept) have been used to inhibit TNF
alpha activity. Controlled trials have demonstrated efficacy for infliximab
in moderately to severely active Crohn's disease (CD) and fistulizing CD s
ufficient to justify recent U.S. Food and Drug Administration (FDA) approva
l. Additional trials have been completed in rheumatoid arthritis (RA). Simi
larly, preliminary controlled trials have suggested efficacy for CDP571 in
active CD and RA. Larger controlled trials have demonstrated efficacy for e
tanercept in RA patients who have failed disease modifying antirheumatic dr
ug (DMARD) therapy leading to FDA approval for RA. Toxicities observed with
anti-TNF therapies have included formation of human antichimeric antibodie
s (HACA) with associated acute and delayed hypersensitivity infusion reacti
ons, human antihuman antibodies (HAHAs), and formation of autoantibodies wi
th rare instances of drug-induced lupus. Several cases of non-Hodgkin's lym
phoma also has been described. Future studies should evaluate optimal timin
g and duration of anti-TNF therapy, the utility of adjuvant medical treatme
nts during anti-TNF therapy, and evaluate long-term safety and efficacy of
the various anti-TNF agents.