Benefit of interferon beta-1a on MSFC progression in secondary progressive MS.
BACKGROUND
Interferon beta-1a (IFNbeta-1a, Avonex) is efficacious in relapsing forms of MS. Studies of other IFNbeta preparations in secondary progressive MS (SPMS) yielded conflicting results. This study was undertaken to determine whether IFNbeta-1a slowed disease progression in SP-MS.


METHODS
A total of 436 subjects with SPMS and Expanded Disability Status Scale (EDSS) score 3.5 to 6.5 were randomized to receive IFNbeta-1a (60 micro g) or placebo by weekly intramuscular injection for 2 years. The primary outcome measure, used for the first time in a large-scale MS trial, was baseline to month 24 change in the MS Functional Composite (MSFC), comprising quantitative tests of ambulation (Timed 25-Foot Walk), arm function (Nine-Hole Peg Test [9HPT]), and cognition (Paced Auditory Serial Addition Test [PASAT]).


RESULTS
Median MSFC Z-score change was reduced 40.4% in IFNbeta-1a subjects (-0.096 vs -0.161 in placebo subjects, p = 0.033), an effect driven mainly by the 9HPT and PASAT. There was no discernible benefit on the EDSS, which in this range principally reflects walking ability. IFNbeta-1a subjects had 33% fewer relapses (p = 0.008). There was significant benefit on eight of 11 MS Quality of Life Inventory subscales. New or enlarging T2-hyperintense brain MRI lesions and gadolinium-enhancing lesions were reduced at months 12 and 24 (both p < 0.001). IFNbeta-1a was well tolerated by the majority of subjects. Neutralizing antibodies developed in 3.3% of IFNbeta-1a-treated subjects.


CONCLUSIONS
IFNbeta-1a demonstrated benefit on MSFC progression, relapses, quality of life, and MRI activity in SPMS.
Cohen
J A
JA
Mellen Center for Multiple Sclerosis Treatment and Research, Department of Neurology, Cleveland Clinic Foundation, OH 44195, USA. cohenj@ccf.org
Cutter
G R
GR
Fischer
J S
JS
Goodman
A D
AD
Heidenreich
F R
FR
Kooijmans
M F
MF
Sandrock
A W
AW
Rudick
R A
RA
Simon
J H
JH
Simonian
N A
NA
Tsao
E C
EC
Whitaker
J N
JN
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage* / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D011788:Quality of Life; D012008:Recurrence; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D016899:Interferon-beta; D000068556:Interferon beta-1a