Sunday, February 03, 2008

Neutralizing Antibodies against Natalizumab

editorial Freedman MS, Pachner AR. Neutralizing antibodies to biological therapies: A "touch of grey" vs. a "black and white" story. Neurology 2007; 69:1386-1388.
based on article Calabresi PA, Giovannoni G, Confavreux C et al. The incidence and significance of antinatilizumab antibodies : results from AFFIRM and SENTINEL. Neurology 2007; 69: 1391-1403.

Cut to the chase:
from the editorial "With natalizumab, NAb's develop quickly, are readily measured, and can be shown to correspond with a loss of activity against a validated disease measure (eg. MR). With IFN B, NAbs develp more slowly, can spontaneously resolve and reappear depedning on titer and are not completely time synchronous with their effect on disease measures. " NAbs correlate (with natalizumab) with new MRI lesions, increased number of relapses, and progression of disability. Editorial notes the gray areas: some patients have NAbs and no re-emergence of disease, relapse rates are only higher inthe persistent NAbs group, and the persistent groups has more infusion reactions early, in the first few months of therapy, before its possible to identify the persistent NAbs group. The lack of persistence in AB might be due to antibodies to the antibodies. NAbs titers are not important.

In the Calabresi article, authors note that 9 % of patients in AFFIRM had NAbs, 3 % transiently and 6 % persistently. SENTINEL results were similar to AFFIRM.

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