The RESTORE trial: What did we learn about multiple sclerosis?
RESTORE was a randomized, partially placebo-controlled exploratory study evaluating multiple sclerosis (MS) disease activity during a 24-week interruption of natalizumab. The objectives of RESTORE were to explore the course of MS disease activity and the effects on pharmacokinetic, pharmacodynamic, and immune parameters in patients undergoing an interruption of natalizumab therapy for up to 24 weeks as compared with those in patients remaining on natalizumab. It also assessed the effects of alternate therapies during natalizumab interruption and after restarting natalizumab. Patients with MS receiving natalizumab were randomized into three treatment arms in a 1:1:2 ratio: natalizumab:placebo:alternate immunomodulatory therapy (interferon b-1a, glatiramer acetate or methylprednisolone).
A total of 175 patients were enrolled. At the baseline visit, all patients received a standard 300-mg natalizumab infusion. Starting at week 4, patients randomized to natalizumab or placebo received infusions every four weeks through to week 24 in a double-blind fashion. Patients randomized to other therapies who chose interferon b-1-a (IM IFN-b-1a) or glatiramer acetate (GA) received their first injections on day 0. Patients randomized to other therapies who chose methylprednisolone (MP) received infusions every four weeks starting at week 12. Clinical, MRI, and laboratory evaluations were performed every four weeks during the randomized treatment period starting at week 0, at the time of suspected relapse, and at the final visit. At week 28, patients resumed open-label infusions of natalizumab and stopped placebo or other therapy. Participants were followed for an additional 24 weeks, concluding the study at week 52.
Disease recurred in a large proportion of RESTORE patients who discontinued natalizumab treatment. The safety evaluations were generally consistent with the labeled risk profile for each of the respective marketed products, notably for natalizumab. Natalizumab treatment interruption resulted in occurrence of MRI disease activity as early as 12 weeks, and of clinical disease activity as early as 4–8 weeks, after the last natalizumab dose. Relapses occurring during the first one to three months have also been observed. In RESTORE, GA starting after the last dose of natalizumab and monthly MP starting 12 weeks after the last natalizumab dose did not appear to be effective in disease suppression, as compared with continued natalizumab treatment.
Neurology. 2014 Apr 29;82(17):e155-7. doi: 10.1212/WNL.0000000000000423.
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