Postnatalizumab
return of disease raised concern that the washout may harm the patient
by a severe relapse with incomplete recovery.
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 over 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 over 400 cases of natalizumab-related PML to date.2Because
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.
