Re: natalizumab and Antegren

[Guest guest]

Tom:

The letter you posted from researchers skeptical of the results of

natalizumab/Antegren/Tysabri is interesting, but I think the rebuttal

from the folks who did the study is worth noting. I do think there

is some reason for optimism with this treatment:

The authors reply: Chaudhuri and Behan refer to an early exploratory

study of natalizumab in multiple sclerosis. This was a study of 72

patients, of whom 37 were randomly assigned to receive two doses of

natalizumab, one month apart (and 35 to receive placebo).1 There was

a significant decrease in the number of new gadolinium-enhanced

lesions on MRI during the 12 weeks after the first dose of

natalizumab, as compared with placebo. Given the small size of the

study and the limited duration of treatment, however, it is not

surprising that no clinical benefit was observed. The positive MRI

result did, however, provide us with a reason to undertake our six-

month study. Although this study was powered only to investigate the

effect of treatment on MRI activity, it showed a significant

treatment-associated reduction in relapses. It is not surprising that

there was no significant change in disability in either the treated

groups or the placebo group over a six-month period.

The mechanisms by which irreversible disability develops in multiple

sclerosis are not well understood. Chaudhuri and Behan cite evidence

supporting the independence of the progression of disability and

relapses,2,3 but these events are not completely unrelated.

Incomplete recovery from relapses is one mechanism of permanent

disability. The effect of natalizumab on long-term progression of

disability can be addressed only by larger, longer-term, phase 3

studies. Two such studies designed to investigate this issue are

currently under way.

In our article, we omitted acknowledgment of J. O'Riordan and J.

Parratt (Ninewells Hospital, Dundee, United Kingdom), who were

investigators in the trial, and Dr. , who provided

helpful comments on the manuscript.

H. , M.D.

Institute of Neurology

London WC1N 3BG, United Kingdom

d.miller@...

W. O'Connor, M.D.

University of Toronto

Toronto, ON M5B 1W8, Canada

Editor's note: Dr. reports having received grant support from

Elan, Schering, and Biogen; honorariums for giving expert advice to

Biogen, Wyeth, Bristol-Myers Squibb, and Schering; and lecture fees

from Serono. Dr. O'Connor reports having received grant support from

Elan, Biogen, Athena Neurosciences, Aventis, Berlex, Serono, Teva

Neurosciences, Angiotech, and Amgen