Highlights
- •People with advanced (“progressive”) MS (pwPMS) currently have only one licensed disease modifying treatment (DMT) option (ocrelizumab), and this option is highly restricted to a specific MS subpopulation living in high cost economies.
- •The cerebro-spinal fluid (CSF) neurofilament light chain (NfL) level is a sensitive index of ongoing neuro-axonal damage.
- •pwPMS who had significantly elevated NfL levels alongside MRI detectable disease activity, were treated using off-label injectable cladribine.
- •Cladribine was well tolerated without any side effects and led to reduction of disease activity as indicated by a substantial drop in CSF NfL concentration alongside reduction in active MRI lesions, whilst total lymphocyte counts remained within the normal reference range.
Abstract
Background
Evidence suggests people with non-relapsing deteriorating (“progressive”) multiple
sclerosis (pwPMS) may benefit from disease-modifying immune therapy (DMT). However,
only one such treatment (ocrelizumab) has been licensed and is highly restricted to
pwPMS suffering from the primary progressive phenotype. The difficulties assessing
treatment outcome in pwPMS is one important reason for the lack of respective DMT.
The concentration of neurofilaments in the cerebrospinal fluid (CSF) provides a biomarker
of neuro-axonal damage, and both neurofilament light (NfL) and heavy chain (NfH) levels
have been used as outcome indices and to guide treatment choices.
Methods
We report on two pwPMS, who were treated with subcutaneous cladribine undergoing CSF
NfL testing, alongside MRI and clinical follow-up, before and after treatment.
Results
Cladribine treatment was well tolerated without any side effects. CSF NfL after treatment
revealed significant reduction (by 73% and 80%, respectively) corroborating the MRI
detectable drop in disease activity. Disability mildly progressed in one, and remained
stable in the other pwPMS.
Conclusions
pwPMS with detectable disease activity (MRI, elevated NfL) should be considered for
DMT. NfL appears to be a sensitive index of treatment effect in pwPMS, and may be
a useful outcome in clinical trials targeting this patient group. Over and above its
licensed indication (relapsing MS), cladribine may be an effective treatment option
for pwPMS.
Keywords
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Article info
Publication history
Published online: May 15, 2018
Accepted:
May 11,
2018
Received in revised form:
April 18,
2018
Received:
January 30,
2018
Identification
Copyright
© 2018 Published by Elsevier B.V.
