- A phase three trial and subsequent three-year follow-up period examined natalizumab in secondary progressive MS
- The initial phase of the trial did not show the treatment to be effective in slowing the main measures of progression, based mainly on lower limb mobility, but did show slowing of disability progression in hand and arm function
- The follow-up study also suggested a delayed effect in slowing disability progression overall
- The study indicates that future trials for progressive MS treatments should include longer term follow-up and upper limb measures of function
Traditionally, MS has been categorised into different types based on the course the disease takes, with a relapsing-remitting course being the most common type of MS. Secondary progressive MS can follow on from this phase, involving a gradual accumulation of disability over time.
Around 10 per cent of people with MS are diagnosed with a progressive course right from the onset, which is known as primary progressive MS. However, there is often no clear demarcation of the different disease stages.
It is thought that inflammation drives the relapsing stage of the disease, whereas neurodegenerative processes drive the progressive forms of the disease. This underpins the reasoning as to why immune-modulating treatments developed for relapsing-remitting MS have had limited effects on progressive MS.
However, results from a trial of relapsing MS medication, natalizumab (Tysabri), in secondary progressive MS, published in Lancet Neurology, suggest that suppressing inflammation in the central nervous system can still help to slow disability accumulation even after significant function has been lost.
The phase three clinical trial with an extended follow-up period enrolled 889 people with secondary progressive MS (SPMS), who were randomly allocated into two groups. The first group received natalizumab for two years, whilst the second group received a ‘sham treatment’. Participants were assessed every 12 weeks using the EDSS score (Expanded Disability Status Scale – a scoring system used to quantify disability in MS), the time it took them to walk 25 metres, and the ‘nine-hole peg test’, which tests upper limb function (arm and hand function) by timing an individual placing pegs into holes on a board.
Following the initial period of the trial, the participants were given the opportunity to continue in the extension phase, with all participants receiving natalizumab during this period. 556 people continued in the study and were followed for an additional three years.
At the end of the first part of the trial, there was no significant difference in the number of people who experienced progression, as measured by the EDSS score and the timed 25 metre walk. The scientists did, however, report a statistically significant difference in the nine-hole peg test, with participants who received natalizumab performing better, suggesting that this medication was delaying disabilities in the arms and hands.
After the follow-up in the extension study, the number of people who had experienced disability progression was much lower among members of the group that received natalizumab from the start of the trial (52 per cent) compared to those who initially had received the sham treatment (61 per cent). This suggests that the drug may have a delayed effect on disability progression that could not be detected during the first phase of the trial. Those who had received natalizumab from the beginning of the trial also retained considerably more function in their arms and hands, as seen in the nine-hole peg test compared to those who had originally received the sham treatment.
These results are encouraging, showing that significant benefits can still be gained from anti-inflammatory treatments in more advanced forms of MS. The results also highlight the great need to incorporate more measures of disability and function in progressive MS trials that look beyond the lower limb function and mobility, as well as longer-term follow-up to identify delayed responses to treatment.
With thanks to MS Research Australia – the lead provider of research summaries on our website.