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

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.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.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).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.