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Abstract
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.
GLOSSARY
- CI=
- confidence interval;
- DTI=
- diffusion tensor imaging;
- EDSS=
- Expanded Disability Status Scale;
- GdEL=
- gadolinium-enhancing lesion;
- GM=
- gray matter;
- MBP=
- myelin basic protein;
- MMP9=
- matrix metalloproteinase-9;
- MS=
- multiple sclerosis;
- MTR=
- magnetization transfer ratio;
- NAWM=
- normal-appearing white matter;
- NFL=
- neurofilament light chain;
- PBVC=
- percentage brain volume change;
- PPMS=
- primary progressive multiple sclerosis;
- RRMS=
- relapsing-remitting multiple sclerosis;
- SPMS=
- secondary progressive multiple sclerosis
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received September 19, 2013.
- Accepted in final form January 22, 2014.
- © 2014 American Academy of Neurology
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