The Pharmaceutical Journal
Vol 270 No 7231 p44
11 January 2003

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New England Journal of Medicine abstracts 2003;348:24 and 2003;348:15

Selective adhesion molecule inhibitor effective in treating Crohn’s disease ...

NATALIZUMAB (Antegren), a selective adhesion molecule inhibitor, increases rates of clinical response and remission in patients with Crohn's disease, researchers report.

Natalizumab, which is being jointly developed by Biogen and Elan for use in Crohn's disease and multiple sclerosis (MS), is a recombinant, humanised monoclonal antibody that binds to a4 integrin, a specific adhesion molecule, on the surface of immune cells. The companies explain that by binding to a4 integren, natalizumab may stop immune cells from leaving the bloodstream and prevent them from migrating into the gastrointestinal tract in Crohn's disease or the brain in MS and making the disease state worse.

Dr Subrata Ghosh, Western General Hospital, Edinburgh, and colleagues assigned 248 patients with moderate to severe Crohn's disease to receive one of four treatment regimens:

1. Two infusions of placebo

2. One infusion of natalizumab 3mg/kg and one infusion of placebo

3. Two infusions of natalizumab 3mg/kg

4. Two infusions of natalizumab 6mg/kg

Infusions were given four weeks apart.

The researchers say that although the rate of remission in the group that received two infusions of natalizumab 6mg/kg was not different from the rate in the placebo group after six weeks (primary end point), the remission rate was superior at weeks four and eight. All three natalizumab groups had a higher rate of clinical response at weeks four, six and eight than placebo. The onset of treatment effect was evident as early as two weeks after initiation of treatment and the response rate was sustained for up to eight weeks after the second infusion in patients who received two infusions of natalizumab.

The researchers conclude: "On the basis of our short-term study, the efficacy of natalizumab for reducing signs and symptoms of Crohn's disease appears to be at least similar to that of the tumour necrosis factor a-inhibitor infliximab." However, they add that the longer term benefit and safety of natalizumab and its value relative to other therapies for Crohn's disease remain to be defined (New England Journal of Medicine 2003;348:24).

... well as for the treatment of multiple sclerosis

Patients with relapsing multiple sclerosis (MS) who are treated with natalizumab (Antegren) have fewer inflammatory brain lesions and fewer further episodes over a six-month period than those given placebo, researchers confirm.

In a phase II study of 213 patients at 26 sites in the United Kingdom, United States and Canada, researchers found that relapses occurred in 13 patients treated with natalizumab 3mg/kg (n=68) and 14 patients treated with natalizumab 6mg/kg (n=74), compared with 27 patients in the placebo group (n=71). Patients were treated every 28 days for six months.

Reductions in the mean number of new lesions in both natalizumab groups were also seen. The percentage of new lesions per patient during the treatment period was 0.7 per cent in the natalizumab 3mg/kg group, 1.1 per cent in the natalizumab 6mg/kg group and 9.6 per cent in the placebo group.

Those in the placebo group reported a slight worsening in wellbeing whereas those in both natalizumab groups reported an improvement — a finding which should be interpreted with caution, the researchers say.

They comment: "Our results provide evidence of a role of a4 integrin — and the immune cells that express it — in the pathogenesis of acute inflammatory lesions in patients with multiple sclerosis (New England Journal of Medicine 2003;348:15). Phase III trials of natalizumab in MS are under way.

Similar results from this study have been reported previously in The Journal (6 October 2001, p456).