title: MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study.
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.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fox
authors.forename: Bruce A C
authors.initials: BA
authors.lastname: Cree
authors.forename: Jerome
authors.initials: J
authors.lastname: De Sèze
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Douglas
authors.initials: D
authors.lastname: Jeffery
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: Michael
authors.initials: M
authors.lastname: Kaufman
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalbán
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.forename: Britt
authors.initials: B
authors.lastname: Anderson
authors.forename: Amy
authors.initials: A
authors.lastname: Natarajan
authors.forename: Barry
authors.initials: B
authors.lastname: Ticho
authors.forename: Petra
authors.initials: P
authors.lastname: Duda
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D000068717:Glatiramer Acetate; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D000069442:Natalizumab; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use; D011788:Quality of Life; D055502:Secondary Prevention; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000069442:Natalizumab; D018696:Neuroprotective Agents; D010455:Peptides; D000068717:Glatiramer Acetate; D016899:Interferon-beta; D008775:Methylprednisolone