Natalizumab is a very effective drug in relapsing-remitting MS. However, after 24 months on the drug some people can develop a severe infection of the brain known as progressive multifocal leukoencephalopathy (PML).

To prevent PML, people who are classed as ‘high-risk’ (by an antibody test) have to stop treatment. Unfortunately, after stopping natalizumab, there is an increased risk of MS inflammation and relapses.

Switching from natalizumab to an alternative drug (interferon beta, glatiramer acetate or fingolimod) may prevent disease reactivation, but the results of published studies are not conclusive and often conflicting.

A recent paper published in Brain reports an observational study of a large number of Italians with relapsing-remitting MS, who stopped natalizumab therapy. The authors compared the effectiveness of switching to fingolimod versus interferon or glatiramer acetate in controlling disease reactivation.

They found that switching to fingolimod was associated with a 64% reduction in the risk of relapse compared to interferon beta or glatiramer acetate.

They also confirmed a higher risk of relapse in people who had high disease relapses before starting natalizumab. Also, younger patients with shorter disease duration were more at risk of relapse after natalizumab suspension.

Finally, they showed that the probability of relapse was less than 0.5% in the first month after stopping natalizumab suspension, but it grew 3-fold in the second and third months and more than 10 times thereafter.

These results suggest that more aggressive treatments should be considered early in the disease course for people with a very active presentation from the disease onset. Also, a wash-out period (a phase at the end of a clinical trial in which patients receive no treatment, to “wash out” the drugs used from their bodies) lasting more than 1–3 months after stopping natalizumab is no longer acceptable in clinical practice.

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