Journal of Neurology

, Volume 255, Issue 4, pp 480–487

Subgroups of the BENEFIT study: Risk of developing MS and treatment effect of interferon beta-1b


    • Vrije Universiteit Medical Centre
    • Dept. of NeurologyAcademic Hospital Vrije Universiteit
  • L. Kappos
    • University Hospital
  • M. S. Freedman
    • The Ottawa Hospital
  • G. Edan
    • Centre Hospitalier Universitaire
  • H.-P. Hartung
    • Heinrich-Heine-Universität
  • D. H. Miller
    • Institute of NeurologyUniversity College
  • X. Montalbán
    • Hospital Vall d’Hebron
  • F. Barkhof
    • Vrije Universiteit Medical Centre
  • K. Selmaj
    • Medical Academy
  • B. M. J. Uitdehaag
    • Vrije Universiteit Medical Centre
  • S. Dahms
    • Bayer Schering Pharma AG
  • L. Bauer
    • Bayer Schering Pharma AG
  • C. Pohl*
    • Bayer Schering Pharma AG
  • R. Sandbrink*
    • Bayer Schering Pharma AG
  • for the BENEFIT investigators**

DOI: 10.1007/s00415-007-0733-2

Cite this article as:
Polman, C., Kappos, L., Freedman, M.S. et al. J Neurol (2008) 255: 480. doi:10.1007/s00415-007-0733-2



The BENEFIT study examined interferon beta (IFNB)-1b treatment in patients with clinically isolated syndrome (CIS) and ≥ 2 clinically silent brain MRI lesions.


Subgroups of 468 patients (IFNB-1b: n = 292; placebo: n = 176) were created for demographics, clinical, laboratory, and MRI findings at onset. The 'natural' risk of clinically definite MS (CDMS) over 2 years was estimated by Kaplan Meier statistics in placebo-treated patients; the IFNB-1b treatment effect was analysed by Cox proportional hazards regression.


The risk of CDMS was increased in placebotreated patients (overall 45 %) if they were younger (< 30 years: 60%), were cerebrospinal fluid (CSF)-positive (49 %), or had received steroid treatment (48 %). MRI parameters implied a higher risk in placebo-treated patients with ≥ 9 T2-lesions (48%) or ≥ 1 gadolinium (Gd)-enhancing lesions (52 %). The CDMS risk was highest (75 %) in placebo-treated patients with monofocal disease onset displaying MRI disease activity (≥ 1 Gd-lesion) and dissemination (≥ 9 T2-lesions). Treatment effects were significant across almost all subgroups including patients with less disease dissemination/activity at onset (monofocal: 55%; < 9 T2-lesions: 60%; no Gd-lesions: 57%) and patients without steroid treatment for the CIS (62 %). Monofocal patients had greater treatment effects if they had ≥ 9 T2-lesions (61 %), Gd-lesions (58 %), or both (65 %).


This study confirms the impact of age of onset, CSF and MRI findings on risk of conversion from CIS to CDMS. IFNB-1b treatment effect was robust across the study population including patients without MRI disease activity and less clinical or MRI disease dissemination at onset and patients not receiving steroids for the CIS.

Key words

multiple sclerosisCISMRI

Copyright information

© Steinkopff-Verlag 2007