More real-world evidence on the effectiveness of HSCT

Clinical trials and real-world studies (those looking at people receiving treatment in routine healthcare) have shown HSCT can be very effective for some people with MS. But we don’t know how HSCT compares to the most highly effective disease modifying therapies (DMTs).

Several current clinical trials are trying to answer that question, including StarMS. Until we get the results we won’t know for sure. But this week, Professor Paolo Muraro and his colleagues, published a new paper that can give us an indication.

Read the full paper on the journal website

What did the researchers do?

The study looked at data from 621 people who had treatment at two London hospitals.

• 103 had HSCT
• 204 had alemtuzumab (Lemtrada)
• 314 had ocrelizumab (Ocrevus)

Everyone had relapsing remitting MS. Most had previously taken a treatment that didn’t effectively control their MS.

They compared the groups for up to five years following treatment, looking at:

• relapses
• new MRI lesions
• disability worsening and improvement (measured with the EDSS)
• no evidence of disease activity (meaning no new relapses, no new MRI activity and no EDSS progression)

Importantly, they used an analysis technique that helps take into account differences between the groups that aren’t to do with the treatments.

Relapses and MRI activity

HSCT versus alemtuzumab

Results show HSCT was better than alemtuzumab at preventing relapses and new MRI lesions. By the end of the follow-up period, compared with alemtuzumab, people who had HSCT showed:

• lower average number of relapses a year
• more people remaining free of new relapses (89% versus 63%)
• more people remaining free of new MRI lesions (85% versus 71%)

HSCT versus ocrelizumab

Data also showed HSCT was better than ocrelizumab at preventing relapses, but the effect was less prominent. Compared with ocrelizumab, people who had HSCT showed:

• lower average number of relapses a year
• more people may have been free of new relapses (91% vs 81%)
• no difference in MRI activity

Few people in either group showed MRI activity, because both treatments are so effective. So this is one possible reason there was no difference.

Disability improvement

People in the HSCT group were more likely to experience an improvement in disability than those in the alemtuzumab group. But there was no difference between HSCT and ocrelizumab.

Disability worsening

Disability worsening was the same for HSCT and the two DMTs. So in the HSCT group, more effectively reducing relapses didn’t result in less disability worsening.

This may be because HSCT only works on worsening in MS caused by relapses. But it doesn’t affect worsening driven by other processes in the brain that cause nerves to get damaged.

This type of worsening generally happens more when you’ve had MS for longer. Most people in the study already had quite significant disability. So it could be that HSCT might effectively prevent disability worsening in people with mild disability, who hadn’t had MS for very long. We don’t know the answer to this.

Safety

People who had HSCT did experience side effects. This is expected and not significantly different from previous studies. But the study didn’t compare safety between HSCT and the DMTs.

Challenges of real-world data

All real-world studies have some problems. For example, people aren’t randomly assigned to each treatment, like they are in clinical trials. And in this study, people taking ocrelizumab weren’t followed up for as long as the other treatments.

This means we can't know for sure whether the patterns we see in the study, would also be true for other people.

What does this mean for people with MS?

The researchers say that overall, it is still not clear whether doctors should favour HSCT as an alternative to the most highly effective DMTs. The results of StarMS and similar trials in other countries should give us some answers. StarMS completed recruitment at the end of last year, with 94 people taking part, and we expect to hear the results in 2027.