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From the Department of Radiology (Dr. Li) and Division of Neurology (Drs. Zhao and Paty), Department of Medicine, University of British Columbia, Vancouver, Canada.
Address correspondence and reprint requests to Dr. David K.B. Li, Department of Radiology, U.B.C. Hospital, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada.
Objective: To examine MRI changes resulting from treatment of secondary progressive MS (SPMS) with two doses of interferon-beta-1a (Rebif). Background: Interferon-beta (IFN-ß) reduces relapses and delays progression in relapsing-remitting MS, but there are conflicting results on its clinical benefit in SPMS. Methods: In a double-blind, randomized, multicenter, placebo-controlled study (SPECTRIMS), 618 patients received IFN-ß-1a 22 µg, 44 µg, or placebo subcutaneously three times weekly for 3 years. T2 activity and burden of disease (BOD) were measured in 617 patients by using semiannual proton density/T2-weighted (PD/T2) MRI scans. A cohort of 283 patients also had 11 monthly PD/T2 and T1-weighted gadolinium-enhanced (T1-Gd) scans at study start. Results: Treatment reduced median numbers of active lesions per patient per scan (semiannual T2 activity: 0.17, 0.20 and 0.67 for the high dose, low dose, and placebo, p < 0.0001; monthly combined unique activity [T1+T2]: 0.11, 0.22, and 1.00, p < 0.0001) and accumulation of BOD (percent change from baseline to month 36: -1.3, -0.5, and 10.0 for the high dose, low dose, and placebo, respectively; p = 0.0001). MRI benefit was most evident in the subgroup of patients who reported relapses in the 2 years before the study. Neutralizing antibody development was associated with reduction in treatment effect: antibody-positive patients did not show significant differences from placebo at either dose. Conclusions: Interferon-ß-1a used in SPMS showed significant effects on all MRI measures, particularly in patients with relapses in the 2 years before the study.
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