The effect of intramuscular interferon beta-1a on spinal cord volume in relapsing-remitting multiple sclerosis.Dupuy SL, Khalid F, Healy BC, Bakshi S, Neema M, Tauhid S, Bakshi R.
Spinal cord atrophy occurs early in multiple sclerosis (MS) and impacts disability. The therapeutic effect of interferon beta-1a (IFNβ-1a) on spinal cord atrophy in patients with relapsing-remitting (RR) MS has not been explored.
We retrospectively identified 16 consecutive patients receiving weekly intramuscular IFNβ-1a for 2 years [baseline age (mean ± SD) 47.7 ± 7.5 years, Expanded Disability Status Scale score median (range) 1.5 (0-2.5), timed 25-foot walk 4.6 ± 0.7 seconds; time on treatment 68.3 ± 59.9 months] and 11 sex- and age-matched normal controls (NC). The spinal cord was imaged at baseline, 1 and 2 years later with 3T MRI. C1-C5 spinal cord volume was measured by an active surface method, from which normalized spinal cord area (SCA) was calculated.
SCA showed no change in the MS or NC group over 2 years [mean annualized difference (95 % CI) MS: -0.604 mm2 (-1.352, 0.144), p = 0.106; NC: -0.360 mm2 (-1.576, 0.855), p = 0.524]. Between group analysis indicated no differences in on-study SCA change [MS vs. NC; year 1 vs. baseline, mean annualized difference (95 % CI) 0.400 mm2 (-3.350, 2.549), p = 0.780; year 2 vs. year 1: -1.196 mm2 (-0.875, 3.266), p = 0.245; year 2 vs. baseline -0.243 mm2 (-1.120, 1.607), p = 0.712].
Established IFNβ-1a therapy was not associated with ongoing spinal cord atrophy or any difference in the rate of spinal cord volume change in RRMS compared to NC over 2 years. These results may reflect a treatment effect. However, due to sample size and study design, these results should be considered preliminary and await confirmation.
Fig: Quantification of spinal cord area
Spinal cord volume loss over the disease course has been linked to disability progression in PwMS, whether it be relapsing-remitting MS or progressive forms of MS. The volume loss in spinal cord is thought to occur not only as a direct result of lesions but as an indirect loss due to dying back axons from a lesion elsewhere in the cord or brain (a process termed Wallerian degeneration). This is probably why spinal cord volume loss is an important indicator of disability progression. Along these lines measurements of spinal cord volume loss can be used to study the efficacy of disease modifying treatments, particularly in primary progressive MS.
Here Dupuy et al. study the neuroprotective effect of Avonex (IFNbeta-1a, Biogen) on spinal cord volume loss. At this stage I must point out that this is a small study (a pilot) and measurements are only done over a two year period and therefore the study is unable to tell you about whether Avonex can slow the rate of volume loss, since there is often a lag in treatment effect by several years. Moreover, there is no direct comparison with PwMS not on treatment, but this study simply looks at spinal cord volume loss in those without MS (I don't think including PwMS not on treatment over two years is ethical considering the current availability of treatments that work).
The study found that there was no difference in the rate of volume loss in the spinal cord of those on Avonex compared to those without MS over a two year period. They allude to a treatment effect by Avonex based on the lack of difference between the two groups.
Traditionally, the effect of disease-modifying treatments in MS are not studied owing to methodological difficulties of measuring the cross-sectional area of what is a small structure and it's variability over time. However, previously another group had studied the effect of Rebif (IFNbeta-1a, Biogen) over a four year period in untreated and treated PwMS, and found no difference in the rate of spinal cord volume loss (Lin X et al. Spinal cord atrophy and disability in multiple sclerosis over four years: application of a reproducible automated technique in monitoring disease progression in a cohort of the interferon B-1a (Rebif) treatment trial. JNNP 2003; 73: 1090-4). In the latter study, they found no difference between baseline spinal cord volumes in the RRMS and those without MS, hinting that spinal cord volume loss may not be significant in early MS and may explain the lack of difference in the Avonex treatment group and those without MS! Clearly, this study needs repeating and preferably in a larger group.