Subgroups of the BENEFIT study: risk of developing MS and treatment effect of interferon beta-1b.
BACKGROUND
The BENEFIT study examined interferon beta (IFNB)-1b treatment in patients with clinically isolated syndrome (CIS) and > or = 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 placebo-treated 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 > or = 9 T2-lesions (48%) or > 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 (> or = 1 Gd-lesion) and dissemination (> or = 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 > or = 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.
Polman
Chris
C
Vrije Universiteit Medical Centre, Amsterdam, The Netherlands. ch.polman@vumc.nl
Kappos
Ludwig
L
Freedman
Mark S
MS
Edan
Gilles
G
Hartung
Hans-Peter
HP
Miller
David H
DH
Montalbán
Xavier
X
Barkhof
Frederick
F
Selmaj
Krzysztof
K
Uitdehaag
Bernard M J
BM
Dahms
Susanne
S
Bauer
Lars
L
Pohl
Christoph
C
Sandbrink
Rupert
R
D000328:Adult; D000367:Age Factors; D001323:Autoantibodies / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002490:Central Nervous System / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D018450:Disease Progression; D004311:Double-Blind Method; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy*; D015990:Placebo Effect; D010919:Placebos; D012307:Risk Factors; D013256:Steroids / Q000627:therapeutic use; D016896:Treatment Outcome
D001323:Autoantibodies; D015415:Biomarkers; D010919:Placebos; D013256:Steroids; D000068576:Interferon beta-1b; D016899:Interferon-beta