Effect of interferon-?1b on magnetic resonance imaging outcomes in secondary progressive multiple sclerosis: Results of a European multicenter, randomized, double-blind, placebo-controlled trial

Abstract

A randomized placebo‐controlled trial of interferon‐β1b was performed on 718 patients with secondary progressive multiple sclerosis with follow‐up of up to 3 years. In addition to clinical variables, serial magnetic resonance imaging (MRI) studies were performed to determine the effect of treatment on the pathological evolution of the disease. All patients eligible for MRI had annual proton density/T2‐weighted brain scans from which total lesion volume was measured and the number of new and enlarging lesions noted. A subgroup of 125 patients also underwent monthly gadolinium‐enhanced and proton density/T2‐weighted brain MRI from months 0 to 6 and 18 to 24 to determine the effect of treatment on the frequency of new lesion activity, defined as new enhancing lesions and new/enlarging T2 lesions not enhancing with gadolinium. The difference in total lesion volume between treatment groups was highly significant. In the placebo group, there was an increase of 15% from baseline to last scan, whereas in the interferon‐β1b group, a reduction of 2% was seen. Within the placebo group, there was a significant year‐on‐year increase in total lesion volume, with a mean increase of 16% at year 3 compared with baseline. In the treated group, there was a significant reduction at year 1 (4%) and year 2 (5%) compared with baseline; the 2% decrease at year 3 was not significant. The number of new or enlarging proton density/T2 lesions was also significantly reduced by treatment. In the frequent MRI subgroup, treatment was associated with a significant 65% reduction in new lesion activity between months 1 and 6, and 78% reduction from months 19 to 24. Interferon‐β1b has a substantial and sustained effect on reducing the accumulation of new inflammatory disease foci in secondary progressive MS. This therapeutic mechanism may contribute to the positive clinical benefits of treatment on the progression of sustained neurological disability and relapse activity that were also identified in this trial.

Review of automatic segmentation methods of multiple sclerosis white matter lesions on conventional magnetic resonance imaging

“…Over the last decade, a number of immunomodulatory and immunosuppressive therapies have been approved for clinical use based primarily on demonstration of their ability to suppress focal inflammatory activity, i.e., lesion formation, and clinical relapses (Comi et al, 2001;Leary et al, 2003;Li and Paty, 1999;Li et al, 2001;Miller et al, 1999;Paty and Li, 1993;Simon et al, 1998;Simon et al, 2000;Zhao et al, 2000). Development of these therapies has been critically dependent on MRI because of the ability of MRI to visualize lesion formation with an order of magnitude greater sensitivity than clinical observation is able to detect relapses The number and volume of MS lesions represent the "burden of disease" and are predictive of patients' clinical course over the long term (O'Riordan et al, 1998).…”

Subgroups of the BENEFIT study: Risk of developing MS and treatment effect of interferon beta-1b

“…Interferon beta-1b (IFNB-1b) administered subcutaneously (sc) every other day (eod) has been demonstrated to be a beneficial treatment for patients with relapsing-remitting multiple sclerosis (RRMS) [9,16] and secondary progressive MS [7,14]. Recently, the BEtaferon/BEtaseron in Newly Emerging MS For Initial Treatment (BENEFIT) study showed that IFNB-1b sc eod is also effective at slowing the development of recurrent active disease from a first clinical event (clinically isolated syndrome; CIS) to the second event, suggesting that this therapy should be considered as a therapeutic option immediately after presentation of the disease [11].…”

Imaging of multiple sclerosis: Role in neurotherapeutics

“…Thus far, all clinically useful disease modifying agents developed for MS have some measurable effect on Gd enhancement activity, but not all drugs with an effect on Gd enhancements have shown clinical benefits ( Table 2). 48,50,51,[62][63][64][65] The apparent MRI-clinical uncoupling is, at least in part, related to defects in trial design. It is possible that drugs could have a beneficial effect on clinical disease without an effect on enhancement, but this appears unlikely for any anti-inflammatory agents.…”

“…Nonetheless, these estimates show sensitivity to change over time and for detecting treatment effects. [47][48][49][50][51] As seen in Table 1, the longitudinal changes on various measures of T2-hyperintense lesions in placebo-assigned subjects have varied among studies. Some of these differences can be attributed to patient characteristics with activity levels over a given time interval seemingly higher in the earlier stages of the disease than in cohorts selected for secondary progressive (SP) disease at entry, by enrichment for subjects with active MRI scans at entry into short-term trials, and by improvements in imaging protocols over time.…”