Safety and efficacy of autologous hematopoietic stem-cell transplantation following natalizumab discontinuation in aggressive multiple sclerosis.

BACKGROUND AND PURPOSE: Natalizumab (NTZ) is a highly effective treatment for relapsing-remitting multiple sclerosis (MS), but its withdrawal is often followed by disease reactivation or rebound, even if other disease-modifying treatments (DMTs) are administered. In this study, for the first time, the safety and efficacy of autologous hematopoietic stem-cell transplantation (aHSCT) performed following NTZ discontinuation were retrospectively compared with conventional DMTs. METHODS: Patients with relapsing-remitting MS treated with NTZ who discontinued the drug after at least six administrations and with at least 6 months of follow-up were included. Patients underwent aHSCT after a minimum of 6 months following NTZ withdrawal, receiving meanwhile cyclophosphamide or corticosteroids, or other DMTs approved for MS (control group) after an adequate wash-out period. Both hematological and neurological follow-up were assessed according to standard policies. RESULTS: A total of 52 patients were included, 11 who received aHSCT and 41 who received DMTs. Baseline clinical and demographic characteristics were similar between the two groups. No fatality or life-threatening complications, including progressive multifocal leukoencephalopathy, were observed. At 3 years following NTZ discontinuation, no evidence of disease activity was reported in 54.5% of the patients in the aHSCT group compared with 11.5% of those in the DMT group (P = 0.0212). Disease reactivation in the patients with aHSCT was observed only during wash-out/bridging therapy and 100% of the cases were free from disease activity after aHSCT. CONCLUSIONS: These data suggest that an aggressive therapy should be established after NTZ with the shortest possible wash-out period. aHSCT after 6 months from NTZ withdrawal appears to be safe.

Clinical activity after fingolimod cessation: disease reactivation or rebound?

BACKGROUND AND PURPOSE: There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself or whether it is due to the natural course of highly active multiple sclerosis (MS). Our aim was to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS. METHODS: Patients with relapsing-remitting MS who were treated with fingolimod for at least 6 months and who stopped treatment for reasons that were unrelated to inefficacy were included in the analysis. RESULTS: A total of 100 patients who had discontinued fingolimod were included in the study. Fourteen patients (14%) had a relapse within 3 months after fingolimod discontinuation, and an additional 12 (12%) had a relapse within 6 months. According to this study's criteria, 10 patients (10%) had a severe reactivation. Amongst these patients, five (5%) had a reactivation that was considered to be a rebound. CONCLUSIONS: The present study showed that more than 26% of patients are at risk of having a relapse within 6 months after fingolimod discontinuation. Nevertheless, the risk of severe reactivations and rebound is lower than has been previously described.