Can you be MS-free?
A hot topic in multiple sclerosis (MS) research circles is the concept of disease activity-free (DAF). As the name suggests, this means that it is possible to have MS without having any evidence of active disease. DAF isn’t “disease-free” – but it may be the next best thing.
When testing the efficacy of a drug, researchers look at different study “endpoints”. The most common is relapse rate or annualized relapse rate, i.e. does the average number of relapses diminish over time? However, there are a number of limitations to this measure. During the course of MS, the frequency of relapses naturally goes down so it can be hard to determine if an improvement in the relapse rate is because of
the drug’s effects. Relapse frequency is also affected by how often you assess it: if you see your doctor once a year, it’s likely that your relapse rate will be lower than if you see the doctor every three months.
Another common endpoint in trials is a change in the MRI. This can mean the number of lesions (plaques), the overall volume of lesions, and so on. However, these measures don’t correlate very well with how you’ll fare in the long run.
The third common endpoint is progression, i.e. has your EDSS score gotten worse over time? Again, this isn’t always an accurate measure since a flare-up can worsen your EDSS score by a point or more, then settle back to where you were before. At its worst point, it’ll seem as if you’re progressing; once disease activity settles down again, there is no net difference in your EDSS. So when you look at this measure will change the interpretation of what’s going on.
DAF is a new, more stringent way of looking at a drug’s effects. It combines relapses, MRI and EDSS progression into one measure. A person who is disease activity-free is experiencing no relapses, no MRI activity and no progression on their EDSS.
How achievable is this? Several studies at the 2012 American Academy of Neurology annual meeting looked at DAF as an endpoint.
Looking at fingolimod (Gilenya), researchers analysed data from the pivotal TRANSFORMS trial that compared fingolimod with Avonex (Khatri et al. AAN 2012; abstract PD5.006). They found that after one year of treatment, 46% of people treated with fingolimod and 34% of people treated with the interferon were disease activity-free.
For BG-12, the oral drug that’s now in development, an analysis of the DEFINE pivotal trial found that the DAF rate was 26-28% with the drug compared to 15% with a placebo (Giovannoni et al. AAN 2012; abstract PD5.005).
For teriflunomide, another oral drug in development, the DAF rate was calculated from data obtained in the TEMSO pivotal trial. The DAF rates were 18-23% with teriflunomide compared to 14% with a placebo (Freedman et al. AAN 2012; abstract PD5.007).
New data were not provided for Tysabri. However, an analysis of AFFIRM trial data was published a few years ago (Havrdova and colleagues. Lancet Neurol 2009;8:254-260). The DAF rate at two years was 37% with natalizumab group and 7% with placebo.
These results suggest that many people – at least one-third – can become free of relapses, MRI changes and progression. If someone isn’t free of disease activity, it isn’t clear if switching therapies will achieve this, but it may be worth discussing with your doctor. One cautionary note, however, is that it hasn’t been established yet if disease activity-free will translate to a lower risk of disability over the long term. But a more exacting standard of drug efficacy may be a step in the right direction in controlling the damage caused by MS.
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