IM interferon beta-1a delays definite multiple sclerosis 5 years after a first demyelinating event.
BACKGROUND
The Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) showed that IM interferon beta-1a (IFNbeta-1a) significantly slows the rate of development of clinically definite multiple sclerosis (CDMS) over 2 years in high-risk patients who experience a first clinical demyelinating event. This report highlights the primary results of a 5-year, open-label extension of CHAMPS (the Controlled High Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurologic Surveillance [CHAMPIONS Study]).


OBJECTIVE
To determine if the benefits of IFNbeta-1a observed in CHAMPS are sustained for up to 5 years.


METHODS
CHAMPS patients at participating CHAMPIONS sites were enrolled in the study. All patients were offered, but not required to take, IFNbeta-1a 30 microg IM once weekly for up to 5 years (from CHAMPS randomization). Patients who received placebo in CHAMPS were considered the delayed treatment (DT) group, and patients who received IFNbeta-1a in CHAMPS were considered the immediate treatment (IT) group. The primary outcome measure was the rate of development of CDMS. Additional outcomes included disease state classification at 5 years, annualized relapse rates, disability level at 5 years (Expanded Disability Status Scale), and MRI measures at 5 years.


RESULTS
Fifty-three percent (203/383) of patients enrolled in CHAMPIONS (n = 100, IT group; n = 103, DT group) and 64% (32/50) of CHAMPS study sites participated in CHAMPIONS. The median time to initiation of IFNbeta-1a therapy in the DT group was 29 months. The cumulative probability of development of CDMS was significantly lower in the IT group compared with the DT group (5-year incidence 36 +/- 9 vs 49 +/- 10%; p = 0.03). Multivariate analysis suggested that the only factors independently associated with an increased rate of development of CDMS were randomization to the DT group and younger age at onset of neurologic symptoms. Few patients in either group developed major disability within 5 years.


CONCLUSIONS
These results support the use of IM interferon beta-1a after a first clinical demyelinating event and indicate that there may be modest beneficial effects of immediate treatment compared with delayed initiation of treatment.
Kinkel
R Philip
RP
Kollman
Craig
C
O'Connor
Paul
P
Murray
Thomas Jock
TJ
Simon
Jack
J
Arnold
Douglas
D
Bakshi
Rohit
R
Weinstock-Gutman
Bianca
B
Brod
Staley
S
Cooper
Joanna
J
Duquette
Pierre
P
Eggenberger
Eric
E
Felton
Warren
W
Fox
Robert
R
Freedman
Mark
M
Galetta
Steven
S
Goodman
Andrew
A
Guarnaccia
Joseph
J
Hashimoto
Stanley
S
Horowitz
Steven
S
Javerbaum
Jeffrey
J
Kasper
Lloyd
L
Kaufman
Michael
M
Kerson
Lloyd
L
Mass
Michelle
M
Rammohan
Kottil
K
Reiss
Merrell
M
Rolak
Loren
L
Rose
John
J
Scott
Thomas
T
Selhorst
John
J
Shin
Robert
R
Smith
Craig
C
Stuart
William
W
Thurston
Stephen
S
Wall
Michael
M
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000276:immunology*; D005500:Follow-Up Studies; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000145:classification / Q000453:epidemiology / Q000517:prevention & control*; D012008:Recurrence; D012044:Regression Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D016899:Interferon-beta; D000068556:Interferon beta-1a