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Neurology. 2014 Apr 29;82(17):1491-8. doi: 10.1212/WNL.0000000000000355. Epub 2014 Mar 28.

MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study.

Author information

1
From the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; University of California San Francisco Multiple Sclerosis Center (B.A.C.C.); Hopital Civil (J.D.S.), Strasbourg, France; St. Josef Hospital (R.G.), Ruhr University, Bochum; Department of Neurology (H.-P.H.), Heinrich-Heine-University, Düsseldorf, Germany; The MS Center at Advance Neurology at Cornerstone Health Care (D.J.), Advance, NC; Departments of Neurology and Biomedicine (L.K.), University Hospital Basel, Switzerland; MS Center (M.K.), Carolinas Medical Center, Charlotte, NC; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Jacobs MS Center and Pediatric MS Center of Excellence (B.W.-G.), Jacobs Neurological Institute, Buffalo, NY; Infusion Communications (B.A.), Haddam, CT; and Biogen Idec Inc. (A.N., B.T., P.D.), Weston, MA.

Erratum in

  • Neurology. 2015 Feb 24;84(8):862. multiple investigator names added.

Abstract

OBJECTIVE:

RESTORE was a randomized, partially placebo-controlled exploratory study evaluating multiple sclerosis (MS) disease activity during a 24-week interruption of natalizumab.

METHODS:

Eligible patients were relapse-free through the prior year on natalizumab and had no gadolinium-enhancing lesions on screening brain MRI. Patients were randomized 1:1:2 to continue natalizumab, to switch to placebo, or to receive alternative immunomodulatory therapy (other therapies: IM interferon β-1a [IM IFN-β-1a], glatiramer acetate [GA], or methylprednisolone [MP]). During the 24-week randomized treatment period, patients underwent clinical and MRI assessments every 4 weeks.

RESULTS:

Patients (n = 175) were randomized to natalizumab (n = 45), placebo (n = 42), or other therapies (n = 88: IM IFN-β-1a, n = 17; GA, n = 17; MP, n = 54). Of 167 patients evaluable for efficacy, 49 (29%) had MRI disease activity recurrence: 0/45 (0%) natalizumab, 19/41 (46%) placebo, 1/14 (7%) IM IFN-β-1a, 8/15 (53%) GA, and 21/52 (40%) MP. Relapse occurred in 4% of natalizumab patients and in 15%-29% of patients in the other treatment arms. MRI disease activity recurred starting at 12 weeks (n = 3 at week 12) while relapses were reported as early as 4-8 weeks (n = 2 in weeks 4-8) after the last natalizumab dose. Overall, 50/167 patients (30%), all in placebo or other-therapies groups, restarted natalizumab early because of disease activity.

CONCLUSIONS:

MRI and clinical disease activity recurred in some patients during natalizumab interruption, despite use of other therapies.

CLASSIFICATION OF EVIDENCE:

This study provides Class II evidence that for patients with MS taking natalizumab who are relapse-free for 1 year, stopping natalizumab increases the risk of MS relapse or MRI disease activity as compared with continuing natalizumab.

PMID:
24682966
PMCID:
PMC4011468
DOI:
10.1212/WNL.0000000000000355
[Indexed for MEDLINE]
Free PMC Article

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