Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes.
OBJECTIVE
To assess efficacy, safety, and tolerability of every-other-day interferon beta-1b treatment in patients with a first clinical event suggestive of multiple sclerosis (MS) (clinically isolated syndrome).


METHODS
We conducted a multicenter, randomized, double-blind, placebo-controlled trial. Patients with a first clinical demyelinating event and at least two clinically silent brain MRI lesions were randomized to interferon beta-1b (IFNB-1b) 250 mug subcutaneously (SC) every other day (EOD) (n = 292) or placebo (n = 176), until clinically definite MS (CDMS) was diagnosed or they had been followed for 24 months.


RESULTS
After 2 years, 45% of placebo patients had converted to CDMS (Kaplan-Meier estimate; primary outcome measure) and 85% fulfilled the McDonald criteria (co-primary outcome measure). Overall interferon beta-1b delayed the time to diagnosis of CDMS (p < 0.0001) and McDonald MS (p < 0.00001). Hazard ratios (95% CI) were 0.50 (0.36 to 0.70) for CDMS and 0.54 (0.43 to 0.67) for McDonald MS favoring treatment with IFNB-1b. Treatment was well tolerated, as indicated by the low rate of patients dropping out of the study before CDMS was reached (6.6% overall, 7.2% in the IFNB-1b group).


CONCLUSIONS
Interferon beta-1b 250 mug subcutaneously every other day delayed conversion to clinically definite multiple sclerosis, and should be considered as a therapeutic option in patients presenting with a first clinical event suggestive of multiple sclerosis.
Kappos
L
L
University Hospital, Basel, Switzerland. lkappos@uhbs.ch
Polman
C H
CH
Freedman
M S
MS
Edan
G
G
Hartung
H P
HP
Miller
D H
DH
Montalban
X
X
Barkhof
F
F
Bauer
L
L
Jakobs
P
P
Pohl
C
C
Sandbrink
R
R
D000328:Adult; D002170:Canada / Q000453:epidemiology; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D007557:Israel / Q000453:epidemiology; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology* / Q000517:prevention & control*; D015990:Placebo Effect; D015995:Prevalence; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D013577:Syndrome; D013997:Time Factors; D016896:Treatment Outcome
D000068576:Interferon beta-1b; D016899:Interferon-beta