Immune surveillance in multiple sclerosis patients treated with natalizumab

Stüve, Olaf; Marra, Christina M.; Jerome, Keith R.; Cook, Linda; Cravens, Petra D.; Cepok, Sabine; Frohman, Elliot M.; Phillips, J. Theodore; Arendt, Gabriele; Hemmer, Bernhard; Monson, Nancy; Racke, Michael K.

doi:10.1002/ana.20858

Cited by 408 publications

(353 citation statements)

References 16 publications

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“…As It is known in from the literature that the concentration of, natalizumab concentrationNTZ progressively decrease within 3 months, whereas changes induced on the immune system could be detected until 6 months after discontinuation (Stüve et al, 2006). Accordingly we found a peak of the risk of relapse risk in the at the 4th th month after discontinuation, and thisthe risk is stillbeing high untilat the 8th month 8 and decreasing at 1-year follow-upwhile after one year it returns to a lower value.…”

Section: Discussionmentioning

confidence: 99%

Long-term management of natalizumab discontinuation in a large monocentric cohort of multiple sclerosis patients

Sangalli

Moiola

Ferré

et al. 2014

Multiple Sclerosis and Related Disorders

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Section: Discussionmentioning

confidence: 99%

Long-term management of natalizumab discontinuation in a large monocentric cohort of multiple sclerosis patients

Sangalli

Moiola

Ferré

et al. 2014

Multiple Sclerosis and Related Disorders

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“…During the washout phase, about a quarter of patients experienced a clinical relapse: these patients also had a higher risk of relapsing during the first 3 months of fingolimod therapy, suggesting that the expected achievement of the historical relapse rate is not prevented by fingolimod when the effect of natalizumab on immune surveillance is declining [14]. Finally, the only statistically significant predictive factor, explaining the disparity in relapse rates between the two groups in this analysis, was whether they received natalizumab previously or not.…”

Section: Discussionmentioning

confidence: 99%

Natalizumab to Fingolimod Switching in Multiple Sclerosis: Results from a Â“Real WordÂ” Retrospective Analysis

Rasia¹,

Cordioli²,

Rossi³

et al. 2015

J Mult Scler

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JMSO, an open access journal Rasia et al., J Mult Scler (Foster City) AbstractFingolimod is an alternative for patients with multiple sclerosis who discontinue natalizumab because of leukoencephalopathy risk. However, the interruption of natalizumab might cause disease reactivation. We aimed to describe the disease course of patients switching to fingolimod after treatment with natalizumab or β-interferon, in a real-world setting, through a retrospective analysis of data in patients with multiple sclerosis that receiving fingolimod at a single centre in Italy. Ninety patients were divided into two groups: patients switching to fingolimod from natalizumab (n = 43, Group 1), and treatment naïve (n=5) plus patients switching from β-interferon (n = 42) (Group 2). In Group 1, the mean annualised relapse rate significantly increased from 0.36 at natalizumab discontinuation to 0.80 after natalizumab washout and 1.12 after the first 3 months of fingolimod, decreasing thereafter to 0.49 by the end of followup. In Group 2, the relapse rate significantly decreased from 1.16 to 0.47 at the end of follow-up. Relapses during natalizumab washout predicted increased disease activity during the first 3 months of fingolimod (p = 0.043). We conclude that fingolimod has a delayed effect in patients switching from natalizumab versus treatment-naïve patients or those switching from β-interferon. Worsening of disease activity during the washout period may be predictive of treatment failure.

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“…It is currently unknown, if the depletion of B cells by rituximab results in PML because of reduced antibody responses against JCV, due to inefficient clearance of latently JCV-infected B cell subsets or perturbation of other functions of B cells such as antigen presentation to T cells (Cooper and Arnold, 2010). Natalizumab reduces not only the migration of CD19 + B cells and CD138 + plasma cells through the blood-brain-barrier (Stuve et al, 2006b), but also perturbs B cell homing by increasing the number of memory-and marginal zone-like B cells in the peripheral blood . The latter conditions and the fact that natalizumab induces the migration of CD34 + progenitor cells to the peripheral blood may influence the shaping and reactivation of neurotropic JCV variants (Frohman et al, 2014;Marshall et al, 2014).…”

Section: Humoral Immune Responses During Jcv Infectionmentioning

confidence: 99%

Immunology of progressive multifocal leukoencephalopathy

Jelčić

Faigle

et al. 2015

J. Neurovirol.

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The high prevalence of asymptomatic JC polyomavirus (JCV) infection in the general population indicates coexistence with the human host and efficient immune control in healthy individuals. For unknown reasons, kidney-resident archetypic JCV strains can turn into neurotropic JCV strains which in hereditary or acquired states of immunodeficiency cause opportunistic infection and cytolytic destruction of glial cells or granule cell neurons resulting in progressive multifocal demyelination in the central nervous system (CNS) or cerebellar atrophy, respectively. Immunomodulatory or immunosuppressive therapies with specific monoclonal antibodies including natalizumab, efalizumab, and rituximab have increased the risk of progressive multifocal leukoencephalopathy (PML) among treated patients, highlighting that symptomatic JCV infection of the CNS is associated with disturbances of adaptive immunity affecting B cells, antibodies, and CD4(+) and/or CD8(+) T cells. To date, no specific therapy to overcome PML is available and the only way to eliminate the virus from the CNS is to reconstitute global immune function. However, since the identification of JCV as the causative agent of PML 40 years ago, it is still not fully understood which components of the immune system prevent the development of PML and which immune mechanisms are involved in eliminating the virus from the CNS. This review gives an update about adaptive JCV-specific immune responses.

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Immune surveillance in multiple sclerosis patients treated with natalizumab

Abstract: These data suggest that natalizumab treatment results in a prolonged decrease of lymphocytes in the CSF and are consistent with the hypothesis that natalizumab impairs immune surveillance of the central nervous system.

Cited by 408 publications

References 16 publications

Long-term management of natalizumab discontinuation in a large monocentric cohort of multiple sclerosis patients

Long-term management of natalizumab discontinuation in a large monocentric cohort of multiple sclerosis patients

Natalizumab to Fingolimod Switching in Multiple Sclerosis: Results from a Â“Real WordÂ” Retrospective Analysis

Immunology of progressive multifocal leukoencephalopathy

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