IFNbeta lowers MMP-9/TIMP-1 ratio, which predicts new enhancing lesions in patients with SPMS.

OBJECTIVE: To 1)determine serum levels of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in patients with secondary progressive (SP) MS; 2)determine the relationship between these serum levels and MRI activity; and 3) evaluate the effect of interferon (IFN) therapy on these measures. BACKGROUND: High serum levels of MMP-9 and low levels of TIMP-1 predict the appearance of new gadolinium-enhancing (Gd+) lesions in relapsing-remitting (RR) MS. METHODS: Monthly Gd+ brain MRI and measures of serum MMP-2, MMP-9, TIMP-1, and TIMP-2 at 3-month intervals were performed for up to 3 years in 33 patients with SPMS participating in a phase III study of IFNbeta-1b. RESULTS: Patients who developed new Gd+ lesions had higher levels of MMP-9 than patients who did not develop Gd+ lesions (median 351 vs 226 ng/mL, p = 0.049). The ratio of MMP-9/TIMP-1 predicted new Gd+ lesion on the concurrent scan (OR = 2.23, 95% CI 0.99 to 4.99, p = 0.052) and on the following scan (OR = 2.16, 95% CI 1.01 to 4.63, p = 0.048), whereas levels of MMP-2/TIMP-2 did not. Median levels of TIMP-1 were higher and MMP-9 trended lower for IFNbeta compared to placebo recipients (TIMP-1: 1,450 vs 1,185 ng/mL, p = 0.024; MMP-9: 225 vs 339 ng/mL, p = 0.081). IFNbeta did not influence levels of MMP-2 and TIMP-2. CONCLUSION: The ratio of MMP-9/TIMP-1 may predict MRI activity in SPMS. The effect of IFNbeta-1b in MS, as measured by reduction in new Gd+ lesions, may be partly explained by altering MMP-9/TIMP-1 ratio.

Interferon beta-1a in children with multiple sclerosis is well tolerated.

BACKGROUND: Multiple sclerosis is a chronic demyelinating disease rare in children. Currently marketed disease modifying therapies are limited to adults. OBJECTIVE: To determine the tolerability of interferon beta-1a (IFNB-1 a) 30 mcg injected intramuscularly once a week in children with clinically definite relapsing-remitting multiple sclerosis (RRMS). DESIGN/METHODS: A standardized questionnaire was sent to neurologists in the United States to determine the tolerability of IFNB-1 a in patients younger than 16 years. RESULTS: Tolerability data were available for 9 of 33 children who were reported to initiate IFNB-1 a. Mean age on initiating treatment was 12.7 years (range 8 - 15) and mean duration of therapy was 17 months (range 5 - 36). No patient discontinued therapy due to an adverse event. CONCLUSIONS: Preliminary data indicate that weekly intramuscular injections of IFNB-1 a are well tolerated.