Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy

Olaf Stuve, P. D. Cravens, Elliot Frohman, J. T. Phillips, G. M. Remington, G. Von Geldern, S. Cepok, M. P. Singh, J. W. Cohen Tervaert, M. De Baets, D. MacManus, D. H. Miller, E. W. Radü, E. M. Cameron, Nancy L Monson, Song Zhang, R. Kim, B. Hemmer, M. K. Racke

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Abstract

OBJECTIVE: Natalizumab is a humanized recombinant monoclonal antibody against very late activation antigen-4 approved for the treatment of patients with multiple sclerosis (MS). A phase II study failed to demonstrate a difference between natalizumab treatment groups and the placebo group with regard to gadolinium enhancing lesions on MRI 3 months after discontinuation of therapy. The objective of this study was to assess clinical MS disease activity, surrogate disease markers on MRI, immunologic parameters in peripheral blood and CSF, as well as safety in patients with MS after discontinuation of natalizumab therapy. METHODS: This study is a longitudinal and serial cross-sectional assessment, in which 23 patients who were treated with natalizumab in the context of two phase III clinical trials were originally enrolled. A subgroup of patients was followed over 14 months. The annual relapse rate, neurologic disease progression assessed by the Expanded Disability Status Scale, disease surrogate markers on MRI, cellular and humoral immune markers in peripheral blood and CSF, and adverse events of the drug were monitored. RESULTS: With regard to clinical disease activity, neuroimaging, and immune responses, the majority of patients in our cohort were stable. Decreased lymphocyte cell numbers and altered cell ratios returned to normal 14 months after cessation of natalizumab. No infectious complications were observed. CONCLUSION: This is the first long-term follow-up of patients who discontinued natalizumab. We did not observe a clinical, radiographic, or immunologic rebound phenomenon after discontinuation of natalizumab therapy.

Original languageEnglish (US)
Pages (from-to)396-401
Number of pages6
JournalNeurology
Volume72
Issue number5
DOIs
StatePublished - Feb 3 2009

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Multiple Sclerosis
Biomarkers
Therapeutics
Integrin alpha4beta1
Antibodies, Monoclonal, Humanized
Phase III Clinical Trials
Gadolinium
Lymphocyte Count
Patient Safety
Natalizumab
Nervous System Diseases
Drug-Related Side Effects and Adverse Reactions
Neuroimaging
Disease Progression
Cell Count
Placebos
Recurrence

ASJC Scopus subject areas

  • Clinical Neurology

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Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy. / Stuve, Olaf; Cravens, P. D.; Frohman, Elliot; Phillips, J. T.; Remington, G. M.; Von Geldern, G.; Cepok, S.; Singh, M. P.; Cohen Tervaert, J. W.; De Baets, M.; MacManus, D.; Miller, D. H.; Radü, E. W.; Cameron, E. M.; Monson, Nancy L; Zhang, Song; Kim, R.; Hemmer, B.; Racke, M. K.

In: Neurology, Vol. 72, No. 5, 03.02.2009, p. 396-401.

Research output: Contribution to journalArticle

Stuve, O, Cravens, PD, Frohman, E, Phillips, JT, Remington, GM, Von Geldern, G, Cepok, S, Singh, MP, Cohen Tervaert, JW, De Baets, M, MacManus, D, Miller, DH, Radü, EW, Cameron, EM, Monson, NL, Zhang, S, Kim, R, Hemmer, B & Racke, MK 2009, 'Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy', Neurology, vol. 72, no. 5, pp. 396-401. https://doi.org/10.1212/01.wnl.0000327341.89587.76
Stuve, Olaf ; Cravens, P. D. ; Frohman, Elliot ; Phillips, J. T. ; Remington, G. M. ; Von Geldern, G. ; Cepok, S. ; Singh, M. P. ; Cohen Tervaert, J. W. ; De Baets, M. ; MacManus, D. ; Miller, D. H. ; Radü, E. W. ; Cameron, E. M. ; Monson, Nancy L ; Zhang, Song ; Kim, R. ; Hemmer, B. ; Racke, M. K. / Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy. In: Neurology. 2009 ; Vol. 72, No. 5. pp. 396-401.
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AU - Stuve, Olaf

AU - Cravens, P. D.

AU - Frohman, Elliot

AU - Phillips, J. T.

AU - Remington, G. M.

AU - Von Geldern, G.

AU - Cepok, S.

AU - Singh, M. P.

AU - Cohen Tervaert, J. W.

AU - De Baets, M.

AU - MacManus, D.

AU - Miller, D. H.

AU - Radü, E. W.

AU - Cameron, E. M.

AU - Monson, Nancy L

AU - Zhang, Song

AU - Kim, R.

AU - Hemmer, B.

AU - Racke, M. K.

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N2 - OBJECTIVE: Natalizumab is a humanized recombinant monoclonal antibody against very late activation antigen-4 approved for the treatment of patients with multiple sclerosis (MS). A phase II study failed to demonstrate a difference between natalizumab treatment groups and the placebo group with regard to gadolinium enhancing lesions on MRI 3 months after discontinuation of therapy. The objective of this study was to assess clinical MS disease activity, surrogate disease markers on MRI, immunologic parameters in peripheral blood and CSF, as well as safety in patients with MS after discontinuation of natalizumab therapy. METHODS: This study is a longitudinal and serial cross-sectional assessment, in which 23 patients who were treated with natalizumab in the context of two phase III clinical trials were originally enrolled. A subgroup of patients was followed over 14 months. The annual relapse rate, neurologic disease progression assessed by the Expanded Disability Status Scale, disease surrogate markers on MRI, cellular and humoral immune markers in peripheral blood and CSF, and adverse events of the drug were monitored. RESULTS: With regard to clinical disease activity, neuroimaging, and immune responses, the majority of patients in our cohort were stable. Decreased lymphocyte cell numbers and altered cell ratios returned to normal 14 months after cessation of natalizumab. No infectious complications were observed. CONCLUSION: This is the first long-term follow-up of patients who discontinued natalizumab. We did not observe a clinical, radiographic, or immunologic rebound phenomenon after discontinuation of natalizumab therapy.

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