Switching multiple sclerosis patients with breakthrough disease to second-line therapy

Tamara Castillo-Trivino, Ellen M. Mowry, Alberto Gajofatto, Dorothee Chabas, Elizabeth Crabtree-Hartman, Bruce A. Cree, Douglas S. Goodin, Ari J. Green, Darin T. Okuda, Daniel Pelletier, Scott S. Zamvil, Eric Vittinghoff, Emmanuelle Waubant

Research output: Contribution to journalArticle

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Abstract

Background: Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown. Methods: This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch. Results: In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p≤0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p≤0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p = 0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004). Conclusions: Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies.

Original languageEnglish (US)
Article numbere16664
JournalPLoS One
Volume6
Issue number2
DOIs
StatePublished - 2011

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immunosuppressive agents
sclerosis
Multiple Sclerosis
relapse
Immunosuppressive Agents
therapeutics
Recurrence
cohort studies
Switches
Cohort Studies
Therapeutics
randomized clinical trials
San Francisco
Natalizumab
Labels
Randomized Controlled Trials
Retrospective Studies
drugs
Odds Ratio
Prospective Studies

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Castillo-Trivino, T., Mowry, E. M., Gajofatto, A., Chabas, D., Crabtree-Hartman, E., Cree, B. A., ... Waubant, E. (2011). Switching multiple sclerosis patients with breakthrough disease to second-line therapy. PLoS One, 6(2), [e16664]. https://doi.org/10.1371/journal.pone.0016664

Switching multiple sclerosis patients with breakthrough disease to second-line therapy. / Castillo-Trivino, Tamara; Mowry, Ellen M.; Gajofatto, Alberto; Chabas, Dorothee; Crabtree-Hartman, Elizabeth; Cree, Bruce A.; Goodin, Douglas S.; Green, Ari J.; Okuda, Darin T.; Pelletier, Daniel; Zamvil, Scott S.; Vittinghoff, Eric; Waubant, Emmanuelle.

In: PLoS One, Vol. 6, No. 2, e16664, 2011.

Research output: Contribution to journalArticle

Castillo-Trivino, T, Mowry, EM, Gajofatto, A, Chabas, D, Crabtree-Hartman, E, Cree, BA, Goodin, DS, Green, AJ, Okuda, DT, Pelletier, D, Zamvil, SS, Vittinghoff, E & Waubant, E 2011, 'Switching multiple sclerosis patients with breakthrough disease to second-line therapy', PLoS One, vol. 6, no. 2, e16664. https://doi.org/10.1371/journal.pone.0016664
Castillo-Trivino T, Mowry EM, Gajofatto A, Chabas D, Crabtree-Hartman E, Cree BA et al. Switching multiple sclerosis patients with breakthrough disease to second-line therapy. PLoS One. 2011;6(2). e16664. https://doi.org/10.1371/journal.pone.0016664
Castillo-Trivino, Tamara ; Mowry, Ellen M. ; Gajofatto, Alberto ; Chabas, Dorothee ; Crabtree-Hartman, Elizabeth ; Cree, Bruce A. ; Goodin, Douglas S. ; Green, Ari J. ; Okuda, Darin T. ; Pelletier, Daniel ; Zamvil, Scott S. ; Vittinghoff, Eric ; Waubant, Emmanuelle. / Switching multiple sclerosis patients with breakthrough disease to second-line therapy. In: PLoS One. 2011 ; Vol. 6, No. 2.
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abstract = "Background: Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown. Methods: This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch. Results: In the within-group analyses, the relapse rate decreased by 70{\%} (95{\%} CI 50,82{\%}; p≤0.001) in switchers to natalizumab and by 77{\%} (95{\%} CI 59,87{\%}; p≤0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6{\%}, p = 0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68{\%} among natalizumab switchers (95{\%} CI 19,87{\%}; p = 0.017) and by 76{\%} among the immunosuppressant switchers (95{\%} CI 36,91{\%}; p = 0.004). Conclusions: Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies.",
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AU - Crabtree-Hartman, Elizabeth

AU - Cree, Bruce A.

AU - Goodin, Douglas S.

AU - Green, Ari J.

AU - Okuda, Darin T.

AU - Pelletier, Daniel

AU - Zamvil, Scott S.

AU - Vittinghoff, Eric

AU - Waubant, Emmanuelle

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N2 - Background: Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown. Methods: This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch. Results: In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p≤0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p≤0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p = 0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004). Conclusions: Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies.

AB - Background: Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown. Methods: This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch. Results: In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p≤0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p≤0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p = 0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004). Conclusions: Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies.

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