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Objective – To study the effect of weekly injected subcutaneous interferon (IFN)- β-1a 22 μg on the extent of brain lesions on magnetic resonance imaging (MRI) and the level of serum matrix metalloproteinase (MMP)-9 in patients with secondary progressive multiple sclerosis (SPMS). Subjects and methods – All the 28 Finnish patients participating in the Nordic multicentre trial on the clinical efficacy of weekly IFN- β-1a (Rebif) 22 μg in SPMS were studied neurologically and by volumetric MRI during a 3-year follow-up. The levels of MMP-9 in serum were measured over the 3-year study. Results – There was no obvious effect on the number of contrast medium-enhancing lesions, the volume of T1 or T2 lesions or level of serum MMP-9, nor was any effect detected on the relapse rate and the Expanded Disability Status Scale (EDSS). Brain atrophy progression was not affected by the treatment. Conclusion – The lack of effect on MRI, clinical outcomes or the levels of MMP-9 indicates that subcutaneous administration of low-dose low-frequency IFN- β-1a is insufficient in controlling either the inflammatory constitutes or the neurodegenerative changes of advanced SPMS. [ABSTRACT FROM AUTHOR]