title: The 11-year long-term follow-up study from the randomized BENEFIT CIS trial.
abstract: OBJECTIVE
  To assess outcomes for patients treated with interferon beta-1b immediately after clinically isolated syndrome (CIS) or after a short delay.
  
  
  METHODS
  Participants in BENEFIT (Betaferon/Betaseron in Newly Emerging MS for Initial Treatment) were randomly assigned to receive interferon beta-1b (early treatment) or placebo (delayed treatment). After conversion to clinically definite multiple sclerosis (CDMS) or 2 years, patients on placebo could switch to interferon beta-1b or another treatment. Eleven years after randomization, patients were reassessed.
  
  
  RESULTS
  Two hundred seventy-eight (59.4%) of the original 468 patients (71.3% of those eligible at participating sites) were enrolled (early: 167 [57.2%]; delayed: 111 [63.1%]). After 11 years, risk of CDMS remained lower in the early-treatment arm compared with the delayed-treatment arm (p = 0.0012), with longer time to first relapse (median [Q1, Q3] days: 1,888 [540, not reached] vs 931 [253, 3,296]; p = 0.0005) and lower overall annualized relapse rate (0.21 vs 0.26; p = 0.0018). Only 25 patients (5.9%, overall; early, 4.5%; delayed, 8.3%) converted to secondary progressive multiple sclerosis. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms (median [Q1, Q3]: 2.0 [1.0, 3.0]). The early-treatment group had better Paced Auditory Serial Addition Task-3 total scores (p = 0.0070). Employment rates remained high, and health resource utilization tended to be low in both groups. MRI metrics did not differ between groups.
  
  
  CONCLUSIONS
  Although the delay in treatment was relatively short, several clinical outcomes favored earlier treatment. Along with low rates of disability and disease progression in both groups, this supports the value of treatment at CIS.
  
  
  BACKGROUND
  NCT01795872.
  
  
  METHODS
  This study provides Class IV evidence that early compared to delayed treatment prolongs time to CDMS in CIS after 11 years.
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ. Ludwig.Kappos@usb.ch.
authors: Ludwig
authors: L
authors: Kappos
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ.
authors: Gilles
authors: G
authors: Edan
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ.
authors: Mark S
authors: MS
authors: Freedman
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ.
authors: Xavier
authors: X
authors: Montalbán
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ.
authors: Hans-Peter
authors: HP
authors: Hartung
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ.
authors: Bernhard
authors: B
authors: Hemmer
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ.
authors: Edward J
authors: EJ
authors: Fox
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ.
authors: Frederik
authors: F
authors: Barkhof
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ.
authors: Sven
authors: S
authors: Schippling
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ.
authors: Andrea
authors: A
authors: Schulze
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ.
authors: Dirk
authors: D
authors: Pleimes
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ.
authors: Christoph
authors: C
authors: Pohl
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ.
authors: Rupert
authors: R
authors: Sandbrink
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ.
authors: Gustavo
authors: G
authors: Suarez
authors: From Neurology (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; CHU-Hopital Pontchaillou (G.E.), Rennes, France; University of Ottawa (M.S.F.), and the Ottawa Hospital Research Institute, Ottawa, Canada; Hospital Universitari Vall d'Hebron (X.M.), Ps. Vall d'Hebron, Barcelona, Spain; Department of Neurology (H.-P.H., R.S.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf; Technische Universität München (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; VU University Medical Center (F.B.), Amsterdam, the Netherlands; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Bayer Pharma AG (A.S., C.P., E.-M.W.), Berlin; Myelo Therapeutics GmbH (D.P.), Berlin; University Hospital of Bonn (C.P.), Germany; and Bayer HealthCare Pharmaceuticals (G.S.), Whippany, NJ.
authors: Eva-Maria
authors: EM
authors: Wicklein
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D003430:Cross-Sectional Studies; D003711:Demyelinating Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068576:Interferon beta-1b / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D008297:Male; D012008:Recurrence; D061665:Time-to-Treatment; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000068576:Interferon beta-1b