Branger P, Parienti JJ, Sormani MP, Defer G. The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis. PLoS One. 2016 ;11(3):e0149685.
BACKGROUND:The quantification of brain atrophy in relapsing-remitting multiple sclerosis (RRMS) may serve as a marker of disease progression and treatment response. We compared the association between first-line (FL) or second-line (SL) disease-modifying drugs (DMDs) and brain volume changes over time in RRMS.
MATERIALS AND METHODS:We reviewed clinical trials in RRMS between January 1, 1995 and June 1, 2014 that assessed the effect of DMDs and reported data on brain atrophy in Medline, Embase, the Cochrane database and meeting abstracts. First, we designed a meta-analysis to directly compare the percentage brain volume change (PBVC) between FLDMDs and SLDMDs at 24 months. Second, we conducted an observational and longitudinal linear regression analysis of a 48-month follow-up period. Sensitivity analyses considering PBVC between 12 and 48 months were also performed.
Among the 272 studies identified, 117 were analyzed and 35 (18,140 patients) were included in the analysis. Based on the meta-analysis, atrophy was greater for the use of an FLDMD than that of an SLDMD at 24 months (primary endpoint mean difference, -0.86; 95% confidence interval: -1.57–0.15; P = 0.02). Based on the linear regression analysis, the annual PBVC significantly differed between SLDMDs and placebo (-0.27%/y and -0.50%/y, respectively, P = 0.046) but not between FLDMDs (-0.33%/y) and placebo (P = 0.11) or between FLDMDs and SLDMDs (P = 0.49). Based on sensitivity analysis, the annual PBVC was reduced for SLDMDs compared with placebo (-0.14%/y and -0.56%/y, respectively, P<0.001) and FLDMDs (-0.46%/y, P<0.005), but no difference was detected between FLDMDs and placebo (P = 0.12).
CONCLUSIONS: SLDMDs were associated with reduced PBVC slope over time in RRMS, regardless of the period considered. These results provide new insights into the mechanisms underlying atrophy progression in RRMS.
As we all should know by now “Time is Brain” and if you are a health professional and don’t know this…shame on you get back to school immediately and read the
So what do you do about it?
If you are a risk adverse person you do nothing and actually take on the risk or should I say your patient takes on the risk, not of the side-effect of the drugs you should be taking, but the damaging effects of uncontrolled MS.
Do nothing and be warned. By the time you want to do something about it, hopefully you may not of missed the boat.
So for the meta analysis of the week this study looks at brain atrophy or should I say the tip of the iceberg of brain atrophy because MRI brain atrophy misses most of the nerve loss, which it is supposed to be measuring.
They look at first line low efficacy drugs, verses the highly effective second line drugs meaning fingolimod and natalizumab verses the CRAB drugs and looked at the volume changes at 2 years.
The secondline shrinkage was 0.27% verses first line 0.33% verse placebo 0.50% , so the take home message is secondline are more active than first line drugs. However the difference isn;t that impressive however, what needs to be takening into acount is that highly effective DMT get rid of swelling so the good drugs make the brain shrink because they are getting rid of swelling so it makes it look like the DMT is causing atrophy. Therefore the way to avoid this issue is to re based line after a year and then see how you are doing. If this were done one may suspect that the second line DMT would do so much better.
This is another response why the ocreluzimab trial was positive because they re-baselined after 12 months to show an effect on slowing atrophy.