J. A. Cohen, MD, G. R. Cutter, PhD, J. S. Fischer, PhD, A. D. Goodman, MD, F. R. Heidenreich, MD, M. F. Kooijmans, MD, PhD, A. W. Sandrock, MD, PhD, R. A. Rudick, MD, J. H. Simon, MD, PhD, N. A. Simonian, MD, E. C. Tsao, PhD and J. N. Whitaker, MD for the IMPACT Investigators*
From the Mellen Center for Multiple Sclerosis Treatment and Research, Department of Neurology (Drs. Cohen, Fischer, and Rudick), Cleveland Clinic Foundation, OH; Center for Research Methodology and Biometrics (Dr. Cutter), AMC Cancer Center, Lakewood, CO; Department of Neurology (Dr. Goodman), University of Rochester, NY; Department of Neurology (Dr. Heidenreich), Hannover Medical School, Germany; Biogen, Inc. (Drs. Kooijmans, Sandrock, Simonian, and Tsao), Cambridge, MA; Department of Radiology (Dr. Simon), University of Colorado, Denver; and Department of Neurology (Dr. Whitaker), University of Alabama at Birmingham.
Interferon ß-1a (IFNß-1a, Avonex) is efficacious in relapsing forms of MS.
Studies of other IFNß preparations in secondary progressive MS (SPMS) yielded conflicting results.
This study was undertaken to determine whether IFNß-1a slowed disease progression in SP-MS.
A total of 436 subjects with SPMS and Expanded Disability Status Scale (EDSS) score 3.5 to 6.5 were randomized to receive IFNß-1a (60 µg) 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]).
Median MSFC Z-score change was reduced 40.4% in IFNß-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.
IFNß-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).
IFNß-1a was well tolerated by the majority of subjects.
Neutralizing antibodies developed in 3.3% of IFNß-1a–treated subjects.
IFNß-1a demonstrated benefit on MSFC progression, relapses, quality of life, and MRI activity in SPMS.
© 2002 American Academy of Neurology