One count in the growing indictment of tumor necrosis factor (TNF) in human pathologies accuses this hyperactive cytokine of complicity in Crohn's disease.
A genetically engineered, humanized antibody that neutralizes TNF not only proved the cytokine guilty as charged, but achieved complete or partial remissions of Crohn's symptoms in nine of 20 patients who received a single intravenous infusion of the antibody.
This clinical improvement tapered off during the active life of the anti-TNF antibody, reaching inactivity after about eight weeks. Of the six patients who achieved total remission at week two, four remained so at week six, and three at week eight.
They were part of a 20-patient cohort of Crohn's sufferers enrolled in a placebo-controlled, randomized clinical study by gastroenterologist C. J. Hawkey at the University of Nottingham, U.K. The Lancet, dated Feb. 22, 1997, reported the trial, which showed "no significant changes in the placebo group" of 10 participants.
The article reported: ". . . there was no significant difference [of treated subjects] from placebo at weeks 4, 6 and 8," and, "We found no evidence of a therapeutic effect that outlasted the disappearance of [the antibody] from the circulation."
"These data," the authors concluded, "suggest that antibody neutralization of TNF-* is a potentially effective strategy in the management of Crohn's disease," but added that the use of their synthetic antibody, (95 percent human sequences; five percent murine), "requires further study."
The Nottingham group has such studies under way to define an optimum dose for its antibody in Crohn's disease, "and to investigate the efficacy of repeated dosing." — David N. Leff