Guest post from Down Under: early treatment works

Guest post: early treatment works; evidence from real life. #MSBlog #MSResearch

"This week we are fortunate to have a guest post from Vilija Jokubaitis and Helmut Butzkueven who run MSBase from Melbourne Australia. MSBase is an ongoing, longitudinal, observational registry open to all practicing neurologists and their healthcare teams. The MSBase registry is ideally suited to clinical outcomes research at a global level as well as the development of regional, multi-centre registries."

Vilija Jokubaitis is a Postdoctoral Research Fellow at University of Melbourne and Helmut Butzkueven is a neurologist and Associate Professor The University of Melbourne. Helmut is the director of MSBase. 

In our recent study, we tried to determine which factors, in early MS could predict or prevent the accumulation of disability. We observed people from their very first neurological symptoms suggestive of MS (Clinically Isolated Syndrome, CIS), for up to 10 years. Average follow-up was 3 years. We took many demographic and clinical factors into consideration including: gender, age at diagnosis, MS-specific disability measures, and also the effect of treatment.

First of all, we looked at the relationship between amount of time people spent on disease modifying therapies (DMT), and how quickly they accumulated disability. Secondly, we looked at the identity of individual drugs that were used, specifically: Avonex, Betaferon, Rebif and Copaxone.

On average, people in our study commenced DMT treatment 8 months after first symptoms (CIS). In our adjusted model, where we considered all of the factors together, we found that patients who had motor symptoms at first presentation were more likely to experience persistent disease worsening at a faster rate than those who did not. In addition, people who were older at diagnosis were more likely to accumulate disability faster. However, we also found that people who persisted on their DMT for greater than 50% of the observation period had a significantly slower rate of disability accumulation than those patients who did not receive treatment. Moreover, there was a step-wise reduction in the rate of disability accumulation the longer people remained on their DMT (up to 75% slower in people who stayed on drug for >80% of the time).

We did not however, find a difference in the rate of disease worsening in patients who spent 50% or less of the time on treatment.  When we looked at individual DMTs, we found that all of the first-line therapies significantly reduced the rate of disability accumulation. There were no significant differences between individual drugs, meaning that they were all as effective as each other.

It has been known for some time now that inflammation in MS and subsequent axonal loss occurs from the earliest disease stages (for more information on this topic, please see previous post. The currently available MS therapies are immunomodulators, meaning that they work by reducing inflammation. Theory tells us that, by inhibiting inflammation, axons can be spared for longer periods and the rate of disability accumulation can be slowed. In this study we have shown just that. People who were treated from very early on in the disease had a slower rate of disability accumulation than those who were not treated. We also provide an argument that these treatments are most effective if used consistently, over a long period of time. The key is finding a DMT that works for the individual and adhering to it. The other positive message from this study is that, irrespective of the symptoms that the individual might have, all first-line DMTs are effective in delaying disability accumulation. In other words, DMTs slow the persistent worsening of the disease whether first symptoms are motor, visual, bladder/bowel, sensory or other.

This graph shows you the effect of show the effect of cumulative DMT exposure versus. no DMT on disease progression. MSers with no exposure do worse over 8 years. 

The consistent and persistent use of DMT from early on in MS therefore slows disability accumulation and prolongs quality of life.

Conflicts: Vilija Jokubaitis has received conference travel support from Novartis. Helmut Butzkueven has served on scientific advisory boards for Biogen Idec, Novartis and Sanofi-Aventis and has received conference travel support from Novartis, Biogen Idec and Sanofi Aventis. He serves on steering committees for trials conducted by Biogen Idec and Novartis, and has received research support from Merck Serono, Novartis and Biogen Idec.

Other MSBase posts:

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