Natalizumab in progressive MS: Results of an open-label, phase 2A, proof-of-concept trial
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Natalizumab in progressive MS : Results of an open-label, phase 2A, proof-of-concept trial. / Romme Christensen, Jeppe; Ratzer, Rikke; Börnsen, Lars; Lyksborg, Mark; Garde, Ellen; Dyrby, Tim B; Siebner, Hartwig R; Sorensen, Per S; Sellebjerg, Finn.
In: Neurology, Vol. 82, No. 17, 29.04.2014, p. 1499-1507.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Natalizumab in progressive MS
T2 - Results of an open-label, phase 2A, proof-of-concept trial
AU - Romme Christensen, Jeppe
AU - Ratzer, Rikke
AU - Börnsen, Lars
AU - Lyksborg, Mark
AU - Garde, Ellen
AU - Dyrby, Tim B
AU - Siebner, Hartwig R
AU - Sorensen, Per S
AU - Sellebjerg, Finn
PY - 2014/4/29
Y1 - 2014/4/29
N2 - 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.
AB - 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.
KW - Adult
KW - Antibodies, Monoclonal, Humanized
KW - Cerebral Cortex
KW - Chemokine CXCL13
KW - Disability Evaluation
KW - Drug Administration Schedule
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Immunologic Factors
KW - Magnetic Resonance Imaging
KW - Male
KW - Matrix Metalloproteinase 9
KW - Middle Aged
KW - Multiple Sclerosis, Chronic Progressive
KW - Myelin Basic Protein
KW - Neurofilament Proteins
KW - Osteopontin
KW - Secondary Prevention
KW - Treatment Outcome
U2 - 10.1212/WNL.0000000000000361
DO - 10.1212/WNL.0000000000000361
M3 - Journal article
C2 - 24682973
VL - 82
SP - 1499
EP - 1507
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 17
ER -
ID: 138617851