Slowing brain shrinkage, effective drugs are better

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

MS Brain Health – Multiple Sclerosis Brain Health initiative

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.

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  • More effective drugs= better makes obvious sense to me but why is it so hard for some doctors to understand? I'm 25 and just diagnosed with RRMS. I want lemtrada as my first drug. Is this a reasonable thing to do? I want to stop any more lesions and stay where I am right now for as long as I can without progressing or my brain shrinking!

    • If you fit the criteria of active disease you may be eligible for lemtrada. Discuss with your neurologists your options and ask if they have the infrastructure to provide lemtrada and their reasons for the choices offered. If they don't have the will get they to refer you to people with the experience.

    • First Time Blogger I have RRMS and my advice to you being just diagnosed is watch your stress and anxiety levels – take up relaxation such as meditation, yoga, Pilates or mindfulness. Your nervous system will appreciate it. Secondly learn how to do self testing for urine infections at home, it's fairly easy. So you are prepared if you have a bacterial infection to get antibiotics from GP.
      All the best H

    • Mouse doctor thanks for the great answer to the commenter's question. I have a friend with a similar question to the one asked. The friend is on 4th neuro, who is finally respecting my friend's choices over her own body and brain. My friend's first non clinic neuro and this non clinic neuro's MRI department failed to pick up a large new lesion and ignored my friend's descriptions of worsening symptoms and kept advising over a long period of time that the Ms is stable on very low efficacy med. Second clinic neuro failed to check the actual MRI images and relied on incorrect MRI reports to advise my friend the Ms is mild and refused to accept pain symptoms being ms related despite pain specialists being unable to find any other cause. Third clinic neuro checked the MRI images, agreed the Ms is neither stable nor 'mild' but refused to work with my friend on my friend's choice of highly effective treatment (neuro agreed friend should be on the highly effectivr treatment just had own ideas on exactly which highly effective treatment). Fourth clinic neuro so far seems to have the capacity to check MRI images as well as reports AND allow my friend to be involved in choosing which poison to infuse into my friend's body. Who says Ms patients are frustrated by their patriarchal treating neuros????

  • MD, do you have a view on how Cladribine would look compared with FLDMDs and SLDMDs? Did you look at brain shrinkage in your work on Cladribine?

  • "Do nothing and be warned. By the time you want to do something about it, hopefully you may not of missed the boat."

    Brilliant, fantastic advice… Except, if you're diagnosed "PPMS", there _is no boat_. And the prospect of the possible future drug "cocktails" talked about on this drug-pushing blog are perhaps not for the fainthearted.

  • What I question is just that I have RRMS discovery 02 years ago, I'm in Copaxone and I am NEDA-3 for now. But I know the effects of drugs on CRABS long treatments: do not hold the progression to SPMS! So I would go for something more effective. In fact I would go for Cladribine. So be here in Brazil or other countries, even for those who have MS active or not, by the will of the patient is often not taken into account ?!

    • Cinara I met with a renowned aus neuro, CEO of Ms research aus and research development officer of Ms research aus to ask this very question. As the neuro was the only clinician in the meeting, the answer fell on his shoulders. His candid answer and the lack of any awareness of the problems associated with his candid answer made me want to bang my head against the wall in frustration. The answer was, effectively, I know I am patriarchal but I believe I know what is best for patients. Bojana

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