The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis

Abstract

The recently completed European trial of interferon beta-1b (IFNbeta-1b) in patients with secondary progressive multiple sclerosis (SP multiple sclerosis) has given an opportunity to assess the impact of treatment on cerebral atrophy using serial MRI. Unenhanced T(1)-weighted brain imaging was acquired in a subgroup of 95 patients from five of the European centres; imaging was performed at 6-month intervals from month 0 to month 36. A blinded observer measured cerebral volume on four contiguous 5 mm cerebral hemisphere slices at each time point, using an algorithm with a high level of reproducibility and automation. There was a significant and progressive reduction in cerebral volume in both placebo and treated groups, with a mean reduction of 3.9 and 2.9%, respectively, by month 36 (P = 0.34 between groups). Exploratory subgroup analyses indicated that patients without gadolinium (Gd) enhancement at the baseline had a greater reduction of cerebral volume in the placebo group (mean reduction at month 36: placebo 5.1%, IFNbeta-1b 1.8%, P < 0.05) whereas those with Gd-enhancing lesions showed a trend to greater reduction of cerebral volume if the patient was on IFNbeta-1b (placebo 2.6%, IFNbeta-1b 3.7%; P > 0.05). These results are consistent with ongoing tissue loss in both arms of this study of secondary progressive multiple sclerosis. This finding is concordant with previous observations that disease progression, although delayed, is not halted by IFNbeta. The different pattern seen in patients with and without baseline gadolinium enhancement suggests that part of the cerebral volume reduction observed in IFNbeta-treated patients may be due to the anti-inflammatory/antioedematous effect of the drug. Longer periods of observation and larger groups of patients may be needed to detect the effects of treatment on cerebral atrophy in this population of patients with advanced disease.

Time-Series Modeling of Multiple Sclerosis Disease Activity: A Promising Window on Disease Progression and Repair Potential?

“…4 An altered role of inflammation in SPMS is documented also from multiple treatment trials in which inflammation was effectively suppressed but accrual of atrophy remained unaltered. [5][6][7] Both clinical characteristics and MRI findings point to a similar picture of slow but accelerated accrual of damage that eventually dissociates from baseline predictors, such as the load of gadolinium-enhancing lesions. Some of the most salient findings are discussed here.…”

“…4 An altered role of inflammation in SPMS is documented also from multiple treatment trials in which inflammation was effectively suppressed but accrual of atrophy remained unaltered. [5][6][7] …”

Interferon-β Treatment for Multiple Sclerosis

“…Brain volumes at baseline (taken as the average of 6 monthly measures prior to study entry) decreased 1.35% during the first year of the study (an average of 12 monthly measurements), then remained relatively stable during the second and third years of follow-up. 81 A trial of IFN␤1b in 95 patients with SPMS 82 showed no significant treatment effect overall on cerebral volumes, but the authors did identify a significant effect in the subgroup of patients who had gadolinium-enhancing lesions at study entry.…”

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

“…Interferon preparations have been shown to slow the rate of brain atrophy in the second year of treatment in RRMS [73][74][75] but not in SPMS [76]. An initial analysis of a study using a less sensitive central brain slice methodology failed to find an effect of copolymer-1 in slowing the rate of brain atrophy [77], but a subsequent…”