title: Long-term safety and effectiveness of natalizumab redosing and treatment in the STRATA MS Study.
abstract: OBJECTIVE
  Report long-term safety and effectiveness of natalizumab over 240 weeks in the prospective, observational, open-label Safety of TYSABRI Re-dosing and Treatment (STRATA) Study.
  
  
  METHODS
  Patients (N = 1,094) previously enrolled in natalizumab multiple sclerosis clinical trials received natalizumab 300 mg IV every 4 weeks, up to 240 weeks. Serious adverse events, Expanded Disability Status Scale (EDSS) scores, and annualized relapse rates were analyzed.
  
  
  RESULTS
  At data cutoff (February 9, 2012), natalizumab exposure was 3,460 patient-years; a median of 56 (range 1-70) infusions were received. Serious adverse events, including progressive multifocal leukoencephalopathy, were consistent with natalizumab's known profile. Upon natalizumab re-exposure, rates of anti-natalizumab antibodies and hypersensitivity reactions were 3% and 5% overall, and 40% and 24% among patients with 1 to 2 prior natalizumab doses. Patients originally randomized to placebo/another disease-modifying therapy vs natalizumab in previous studies had significantly higher EDSS scores at STRATA baseline; this difference persisted over 240 weeks. EDSS scores generally remained stable. Patients initially randomized to natalizumab had lower annualized relapse rates over 240 weeks.
  
  
  CONCLUSIONS
  Serious adverse events were consistent with natalizumab's known safety profile; short exposure with a gap before redosing was associated with higher incidences of anti-natalizumab antibodies and hypersensitivity reactions. Stability of EDSS scores and consistently low relapse rates over 5 years of natalizumab treatment are consistent with its known efficacy profile.
  
  
  METHODS
  This study provides Class III evidence that in patients with relapsing-remitting multiple sclerosis, natalizumab stabilizes EDSS scores, decreases relapse rates, and is associated with an increased risk of progressive multifocal leukoencephalopathy.
authors.affiliation: From the Department of Neurology (P.O.), St. Michael's Hospital, Toronto, Canada; Department of Neurology (A.G.), University of Rochester, NY; Departments of Neurology and Biomedicine (L.K.), University Hospital Basel, Switzerland; Corinne Goldsmith Dickinson Center for MS at The Icahn School of Medicine at Mount Sinai (F.L.), New York, NY; Department of Neurology (C.P.), VU Medical Centre, Amsterdam, the Netherlands; Mellen Center for Multiple Sclerosis Treatment and Research (R.A.R.), Cleveland Clinic Foundation, OH; Infusion Communications (K.H.), Haddam, CT; Departments of Safety and Benefit-Risk Management (L.M.C.) and Biostatistics (F.F.), Biogen Idec Inc., Cambridge; and Sarepta Therapeutics (P.D.), Cambridge, MA; P.D., a former employee of Biogen Idec Inc., was at the company during study conduct. OCONNORP@smh.toronto.on.ca.
authors.forename: Paul
authors.initials: P
authors.lastname: O'Connor
authors.affiliation: From the Department of Neurology (P.O.), St. Michael's Hospital, Toronto, Canada; Department of Neurology (A.G.), University of Rochester, NY; Departments of Neurology and Biomedicine (L.K.), University Hospital Basel, Switzerland; Corinne Goldsmith Dickinson Center for MS at The Icahn School of Medicine at Mount Sinai (F.L.), New York, NY; Department of Neurology (C.P.), VU Medical Centre, Amsterdam, the Netherlands; Mellen Center for Multiple Sclerosis Treatment and Research (R.A.R.), Cleveland Clinic Foundation, OH; Infusion Communications (K.H.), Haddam, CT; Departments of Safety and Benefit-Risk Management (L.M.C.) and Biostatistics (F.F.), Biogen Idec Inc., Cambridge; and Sarepta Therapeutics (P.D.), Cambridge, MA; P.D., a former employee of Biogen Idec Inc., was at the company during study conduct.
authors.forename: Andrew
authors.initials: A
authors.lastname: Goodman
authors.affiliation: From the Department of Neurology (P.O.), St. Michael's Hospital, Toronto, Canada; Department of Neurology (A.G.), University of Rochester, NY; Departments of Neurology and Biomedicine (L.K.), University Hospital Basel, Switzerland; Corinne Goldsmith Dickinson Center for MS at The Icahn School of Medicine at Mount Sinai (F.L.), New York, NY; Department of Neurology (C.P.), VU Medical Centre, Amsterdam, the Netherlands; Mellen Center for Multiple Sclerosis Treatment and Research (R.A.R.), Cleveland Clinic Foundation, OH; Infusion Communications (K.H.), Haddam, CT; Departments of Safety and Benefit-Risk Management (L.M.C.) and Biostatistics (F.F.), Biogen Idec Inc., Cambridge; and Sarepta Therapeutics (P.D.), Cambridge, MA; P.D., a former employee of Biogen Idec Inc., was at the company during study conduct.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.affiliation: From the Department of Neurology (P.O.), St. Michael's Hospital, Toronto, Canada; Department of Neurology (A.G.), University of Rochester, NY; Departments of Neurology and Biomedicine (L.K.), University Hospital Basel, Switzerland; Corinne Goldsmith Dickinson Center for MS at The Icahn School of Medicine at Mount Sinai (F.L.), New York, NY; Department of Neurology (C.P.), VU Medical Centre, Amsterdam, the Netherlands; Mellen Center for Multiple Sclerosis Treatment and Research (R.A.R.), Cleveland Clinic Foundation, OH; Infusion Communications (K.H.), Haddam, CT; Departments of Safety and Benefit-Risk Management (L.M.C.) and Biostatistics (F.F.), Biogen Idec Inc., Cambridge; and Sarepta Therapeutics (P.D.), Cambridge, MA; P.D., a former employee of Biogen Idec Inc., was at the company during study conduct.
authors.forename: Fred
authors.initials: F
authors.lastname: Lublin
authors.affiliation: From the Department of Neurology (P.O.), St. Michael's Hospital, Toronto, Canada; Department of Neurology (A.G.), University of Rochester, NY; Departments of Neurology and Biomedicine (L.K.), University Hospital Basel, Switzerland; Corinne Goldsmith Dickinson Center for MS at The Icahn School of Medicine at Mount Sinai (F.L.), New York, NY; Department of Neurology (C.P.), VU Medical Centre, Amsterdam, the Netherlands; Mellen Center for Multiple Sclerosis Treatment and Research (R.A.R.), Cleveland Clinic Foundation, OH; Infusion Communications (K.H.), Haddam, CT; Departments of Safety and Benefit-Risk Management (L.M.C.) and Biostatistics (F.F.), Biogen Idec Inc., Cambridge; and Sarepta Therapeutics (P.D.), Cambridge, MA; P.D., a former employee of Biogen Idec Inc., was at the company during study conduct.
authors.forename: Chris
authors.initials: C
authors.lastname: Polman
authors.affiliation: From the Department of Neurology (P.O.), St. Michael's Hospital, Toronto, Canada; Department of Neurology (A.G.), University of Rochester, NY; Departments of Neurology and Biomedicine (L.K.), University Hospital Basel, Switzerland; Corinne Goldsmith Dickinson Center for MS at The Icahn School of Medicine at Mount Sinai (F.L.), New York, NY; Department of Neurology (C.P.), VU Medical Centre, Amsterdam, the Netherlands; Mellen Center for Multiple Sclerosis Treatment and Research (R.A.R.), Cleveland Clinic Foundation, OH; Infusion Communications (K.H.), Haddam, CT; Departments of Safety and Benefit-Risk Management (L.M.C.) and Biostatistics (F.F.), Biogen Idec Inc., Cambridge; and Sarepta Therapeutics (P.D.), Cambridge, MA; P.D., a former employee of Biogen Idec Inc., was at the company during study conduct.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rudick
authors.affiliation: From the Department of Neurology (P.O.), St. Michael's Hospital, Toronto, Canada; Department of Neurology (A.G.), University of Rochester, NY; Departments of Neurology and Biomedicine (L.K.), University Hospital Basel, Switzerland; Corinne Goldsmith Dickinson Center for MS at The Icahn School of Medicine at Mount Sinai (F.L.), New York, NY; Department of Neurology (C.P.), VU Medical Centre, Amsterdam, the Netherlands; Mellen Center for Multiple Sclerosis Treatment and Research (R.A.R.), Cleveland Clinic Foundation, OH; Infusion Communications (K.H.), Haddam, CT; Departments of Safety and Benefit-Risk Management (L.M.C.) and Biostatistics (F.F.), Biogen Idec Inc., Cambridge; and Sarepta Therapeutics (P.D.), Cambridge, MA; P.D., a former employee of Biogen Idec Inc., was at the company during study conduct.
authors.forename: Kathy
authors.initials: K
authors.lastname: Hauswirth
authors.affiliation: From the Department of Neurology (P.O.), St. Michael's Hospital, Toronto, Canada; Department of Neurology (A.G.), University of Rochester, NY; Departments of Neurology and Biomedicine (L.K.), University Hospital Basel, Switzerland; Corinne Goldsmith Dickinson Center for MS at The Icahn School of Medicine at Mount Sinai (F.L.), New York, NY; Department of Neurology (C.P.), VU Medical Centre, Amsterdam, the Netherlands; Mellen Center for Multiple Sclerosis Treatment and Research (R.A.R.), Cleveland Clinic Foundation, OH; Infusion Communications (K.H.), Haddam, CT; Departments of Safety and Benefit-Risk Management (L.M.C.) and Biostatistics (F.F.), Biogen Idec Inc., Cambridge; and Sarepta Therapeutics (P.D.), Cambridge, MA; P.D., a former employee of Biogen Idec Inc., was at the company during study conduct.
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Cristiano
authors.affiliation: From the Department of Neurology (P.O.), St. Michael's Hospital, Toronto, Canada; Department of Neurology (A.G.), University of Rochester, NY; Departments of Neurology and Biomedicine (L.K.), University Hospital Basel, Switzerland; Corinne Goldsmith Dickinson Center for MS at The Icahn School of Medicine at Mount Sinai (F.L.), New York, NY; Department of Neurology (C.P.), VU Medical Centre, Amsterdam, the Netherlands; Mellen Center for Multiple Sclerosis Treatment and Research (R.A.R.), Cleveland Clinic Foundation, OH; Infusion Communications (K.H.), Haddam, CT; Departments of Safety and Benefit-Risk Management (L.M.C.) and Biostatistics (F.F.), Biogen Idec Inc., Cambridge; and Sarepta Therapeutics (P.D.), Cambridge, MA; P.D., a former employee of Biogen Idec Inc., was at the company during study conduct.
authors.forename: Fiona
authors.initials: F
authors.lastname: Forrestal
authors.affiliation: From the Department of Neurology (P.O.), St. Michael's Hospital, Toronto, Canada; Department of Neurology (A.G.), University of Rochester, NY; Departments of Neurology and Biomedicine (L.K.), University Hospital Basel, Switzerland; Corinne Goldsmith Dickinson Center for MS at The Icahn School of Medicine at Mount Sinai (F.L.), New York, NY; Department of Neurology (C.P.), VU Medical Centre, Amsterdam, the Netherlands; Mellen Center for Multiple Sclerosis Treatment and Research (R.A.R.), Cleveland Clinic Foundation, OH; Infusion Communications (K.H.), Haddam, CT; Departments of Safety and Benefit-Risk Management (L.M.C.) and Biostatistics (F.F.), Biogen Idec Inc., Cambridge; and Sarepta Therapeutics (P.D.), Cambridge, MA; P.D., a former employee of Biogen Idec Inc., was at the company during study conduct.
authors.forename: Petra
authors.initials: P
authors.lastname: Duda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D000069442:Natalizumab; D019370:Observation; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000069442:Natalizumab