A new meta-analysis of MS drug trials, published in Frontiers in Neurology, has revealed that the efficacy of disease-modifying therapies (DMTs) varies depending on age.1
Given the wide range of DMTs now available for MS, healthcare professionals and people with MS need to be well informed about the relative effectiveness of various treatments at different stages in the disease course. This new study looked at whether the efficacy of available DMTs differs depending on the age of the person treated.
Dr Weideman and colleagues extracted mean data from 38 published clinical trials, then applied a statistical model called linear regression to investigate the relationship between drug efficacy and age. Efficacy was measured by how well each drug prevented disability progression compared (directly or indirectly) with placebo. Together these trials included over 28 000 people with MS and 13 MS drug types (interferon beta preparations and 12 immunomodulatory drugs).
Researchers found that the efficacy of DMTs strongly decreased with advancing age, regardless of disability level at the start of the trial (see figure). Specifically, the model predicted that on average DMTs cease to be effective beyond the age of approximately 53 years. When the low- and high-efficacy DMTs were modelled separately, the high-efficacy drugs were more effective than low-efficacy drugs only when used in people of 40.5 years or younger; after this point there was no benefit in the average person with MS using high-efficacy drugs. The authors highlighted that the continuous loss of efficacy with age reported in this study supports the notion that “progressive MS is simply a later stage of the MS disease process”.
Figure. The relationship between efficacy of MS drugs and age. Reproduced from Weideman et al. Front Neurol. 2017;8:577.1
What does this graph show?
Each coloured circle represents one clinical trial; its position shows the average efficacy of the drug compared with placebo and the average age of participants in that one trial, while the size of the circle indicates the importance of that trial in the statistical model (trials with more participants and a longer duration were given more weight than smaller, shorter trials). The dashed lines show the linear regression statistical model applied to the data – this indicates the average expected efficacy at different ages.
There are limitations to this modelling approach; the analysis included only one trial with mean age over 50 years, for example, and the benefit individuals will experience from DMTs will differ based on genetic and environmental factors. Nevertheless, these findings could help to inform clinicians and people with MS when they are discussing treatment options. The authors concluded, “Delaying any DMT, even for a few years, leads to a decrease in cumulative efficacy that cannot be easily regained by opting for more aggressive treatments at a later age.”
- Weideman AM, Tapia-Maltos MA, Johnson K, et al. Meta-analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments. Front Neurol. 2017;8:577; doi:10.3389/fneur.2017.00577.