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

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Abstract

Background

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

Methods

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.

Results

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 %).

Conclusions

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.

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Author information

Authors and Affiliations

  1. Vrije Universiteit Medical Centre, Amsterdam, The Netherlands

    C. Polman MD, PhD, F. Barkhof & B. M. J. Uitdehaag

  2. University Hospital, Basel, Switzerland

    L. Kappos

  3. The Ottawa Hospital, Ottawa, Canada

    M. S. Freedman

  4. Centre Hospitalier Universitaire, Rennes, France

    G. Edan

  5. Heinrich-Heine-Universität, Düsseldorf, Germany

    H.-P. Hartung

  6. Institute of Neurology, University College, London, UK

    D. H. Miller

  7. Hospital Vall d’Hebron, Barcelona, Spain

    X. Montalbán

  8. Medical Academy, Lodz, Poland

    K. Selmaj

  9. Bayer Schering Pharma AG, Berlin, Germany

    S. Dahms, L. Bauer, C. Pohl* & R. Sandbrink*

  10. Dept. of Neurology, Academic Hospital Vrije Universiteit, 7057, 1007, MB Amsterdam, The Netherlands

    C. Polman MD, PhD

Authors
  1. C. Polman MD, PhD
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  2. L. Kappos
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  3. M. S. Freedman
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  4. G. Edan
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  6. D. H. Miller
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  7. X. Montalbán
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  8. F. Barkhof
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  9. K. Selmaj
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  10. B. M. J. Uitdehaag
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  11. S. Dahms
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  12. L. Bauer
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  13. C. Pohl*
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  14. R. Sandbrink*
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Consortia

for the BENEFIT investigators**

Corresponding author

Correspondence to C. Polman MD, PhD.

Additional information

Data analysis was performed by S. Dahms.

Disclosures

C. Polman has received: consulting fees from Biogen Idec, Bayer Schering Pharma AG, Teva, Serono, Novartis, Antisense, and GlaxoSmithKline; lecture fees from Biogen Idec, Bayer Schering Pharma AG, and Teva and grant support from Biogen Idec, Bayer Schering Pharma AG, Wyeth, and Glaxo-SmithKline.

L.Kappos has received honoraria and research support from the Swiss MS Society, Aventis, Bayer, Berlex, Biogen Idec, Elan, Genzyme, GlaxoSmithKline, Novartis, Bayer Schering Pharma AG, Serono, Teva, Wyeth, and others. These payments were exclusively used for support of MS research at his department.

M. Freedman has received honoraria from Serono, Bayer Schering Pharma AG, Berlex, Teva, Pfizer, and a research grant from Serono.

G. Edan has received honorariua/consulting fees from Novartis, LFB,Aventis, Serono, Bayer Schering Pharma AG; lecture grants from Biogen Idec, Serono, and grant support from Serono, Bayer Schering Pharma AG and Teva.

H.-P. Hartung has received fees for speaking at scientific symposia and honoraria for consulting ad-hoc from Bayer, Biogen Idec, Bayer Schering Pharma AG, Teva, and Serono.

D. Miller has received: honoraria/consulting fees from Biogen Idec, Wyeth, Novartis, UCB Pharma, and Bristol Myers Squibb; lecture fees from Biogen Idec and Serono and grant support from Biogen Idec, GlaxoSmithKline, and Bayer Schering Pharma AG.

X.Montalbán has received: honoraria/consulting fees, grant support and lecture fees from Biogen Idec, Wyeth, Novartis, Serono, Bayer Schering Pharma AG, Bayer Schering España SA and Teva.

F. Barkhof has served as a consultant to various pharmaceutical companies, including Aventis, Wyeth, Astra, Teva, Biogen, Bayer Schering Pharma AG, and Serono. As the director of the Image Analysis Centre, he has been remunerated for time spent conducting the blind MRI analyses.

L. Bauer, S. Dahms†, C. Pohl, and R. Sandbrink are salaried employees of Bayer Schering Pharma AG.

* Both authors contributed equally to the work.

** See the Appendix for a list of the BENEFIT Study Investigators.

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Polman, C., Kappos, L., Freedman, M.S. et al. Subgroups of the BENEFIT study: Risk of developing MS and treatment effect of interferon beta-1b. J Neurol 255, 480–487 (2008). https://doi.org/10.1007/s00415-007-0733-2

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  • DOI: https://doi.org/10.1007/s00415-007-0733-2

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