Objective: Natalizumab
inhibits the migration of systemic immune cells to the CNS and may be
beneficial in progressive multiple sclerosis (MS). The objective of the
study was to examine the effects of natalizumab in progressive MS.
Methods: In
an open-label phase 2A study, 24 patients with progressive MS were
included to receive natalizumab treatment for 60 weeks. Response to
natalizumab was assessed in CSF and MRI studies. The primary endpoint
was change in CSF osteopontin, a biomarker of intrathecal inflammation,
from baseline to week 60.
Results: Seventeen
patients completed the study. No new safety issues were encountered.
CSF osteopontin decreased by 65 ng/mL (95% confidence interval 34–96
ng/mL; p =
0.0004) from baseline to week 60 in conjunction with decreases in other
CSF biomarkers of inflammation, axonal damage, and demyelination.
Magnetization transfer ratio increased in both cortical gray and
normal-appearing white matter and correlated with decreases in CSF
neurofilament light chain.
Conclusions: Natalizumab
treatment of progressive MS reduces intrathecal inflammation and tissue
damage, supporting a beneficial effect of natalizumab treatment in
progressive MS and suggesting that systemic inflammation contributes to
the pathogenesis. Moreover, the study establishes the feasibility of
using CSF biomarkers in proof-of-concept trials, allowing a low number
of participants and short study duration.
Classification of evidence: This
study provides Class IV evidence that in patients with progressive MS,
natalizumab reduces biomarkers of intrathecal inflammation.
http://www.neurology.org/content/early/2014/03/28/WNL.0000000000000361.short?rss=1
