Abstract
With more choices for multiple
sclerosis (MS) disease-modifying therapies, data are urgently required
to support clinical decisions regarding safe transitioning and
sequencing of therapies. With more than 7 years of clinical experience,
natalizumab has been confirmed as highly effective in reducing MS
disease activity. However, natalizumab carries a risk of progressive
multifocal leukoencephalopathy (PML),(1) with more than 400 cases of
natalizumab-related PML to date.(2) Because 2 of the 3 initial
natalizumab-associated PML cases were on the combination natalizumab
plus interferon, the concern was that combining agents led to a
heightened risk of infectious complications. In these early times,
uncertainty revolved around 2 points: the theoretical risk of PML if
natalizumab was transiently combined with another immune-altering agent
and the value of transiently "reconstituting" CNS immune surveillance by
washout of natalizumab in an effort to clear theoretical subclinical JC
virus within the CNS.(3) The optimal length of natalizumab washout
became the subject of intense consternation and debate, with no clear
guidelines to inform practice. However, upon withdrawing natalizumab,
resumption of disease activity was soon observed, beginning 3-4 months
after the last dose of natalizumab.(4-10) Postnatalizumab return of
disease raised concern that the washout may harm the patient by a severe
relapse with incomplete recovery.
Click here to read more
