Anti-interferon antibody shows against Crohn's disease
Last Updated: 2006-07-28 15:00:30 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Fontolizumab, a humanized anti-interferon gamma antibody, is a well-tolerated and effective treatment for moderate to severe Crohn's disease (CD), according to two reports appearing in the August issue of Gut.

Interferon gamma is thought to play a key role in the inflammation seen with Crohn's disease, the authors note. Therefore, treatment with an antibody that can attenuate the effects of this cytokine may provide clinical benefits.

Dr. W. Reinisch, from Universitaetsklinik Innere Medizin IV in Vienna, Austria, and colleagues conducted a dose-escalating, placebo controlled study of fontolizumab in 45 CD patients with a disease activity index of 250 to 450. Fontolizumab was given as a single intravenous dose of 0.1, 1.0, and 4.0 mg/kg.

Subjects who showed a clinical response by day 29 were randomized to receive three additional doses at half the original dose or placebo at four weekly intervals, according to the report.

In general, fontolizumab was well tolerated, the authors state. The higher doses of the antibody were more often associated with chills, flu-like syndrome, asthenia, nausea, and vomiting than was the lowest dose. In addition, two patients showed worsening of their disease while treated with fontolizumab and one patient developed antibodies against the agent.

Although clinical activity parameters did not differ significantly between the groups, the 4.0 mg/kg fontolizumab cohort showed less severe disease on endoscopy and had lower levels of C-reactive protein than the placebo group (p < 0.05 for both).

In a follow-up study to the first, Dr. D. W. Hommes, from the Academic Medical Centre in Amsterdam, the Netherlands, and colleagues assessed the outcomes of 133 CD patients who were randomized to receive fontolizumab, at 4 or 10 mg/kg dose, or placebo. As in the first study, the patients had CD activity index scores between 250 and 450.

Forty-two of the patients received one dose of fontolizumab, while 91 received a dose on day 0 and on day 28.

Just one dose of the agent did not seem to have a significant effect on the primary endpoint, the clinical response at day 28. With two doses, however, a doubling of the response rate was seen at day 56. Patients treated with either dose of fontolizumab had a response rate of about 68% compared with 32% for placebo.

Accounting for baseline elevations in C-reactive protein resulted in an even more pronounced benefit for fontolizumab over placebo.

Two grade 3 adverse events, thought to be related to CD, were noted. One death and one serious adverse event also occurred, but were considered unrelated to fontolizumab therapy.

In a related editorial, Dr. S. Ghosh, from Imperial College London, and colleagues comment that anti-interleukin-12 antibody has also shown promise as a treatment for CD and further studies are needed to determine whether this agent or fontolizumab is "more effective in the treatment of inflammatory bowel disease, including CD and ulcerative colitis."

Fontolizumab is being developed by Fremont, California-based Protein Design Labs, Inc. as HuZAF.

Gut 2006;55:1071-1073,1131-1144.

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