Debate: People with non-relapsing SPMS should have their DMTs stopped - MS Cutting Edge Science
Event reports
This session is part of a series of write-ups on Cutting Edge Science for Multiple Sclerosis 2021; the conference summary for which is here. The conference was chaired by Dr Wallace Brownlee.
Yes: Dr Marco Pisa
Clinicians should stop disease modifying therapies (DMTs) in all non-active progressive patients, argued Dr Marco Pisa.
More recent definitions of MS have moved away from distinguishing between primary and secondary progression, and towards focusing on ongoing progression and inflammatory activity, he explained.
Dr Marco Pisa
The Olympus, Oratorio, and Expand trials show, he said, that those who benefit from treatment are younger, have a shorter disease duration, a lower expanded disability status scale (EDSS) score, and are treatment naïve.
He argued that treatment targets the specific features of early active MS, such as focal inflammatory demyelination and peripheral adaptive immunity, rather than the predominant mechanisms of PMS that drive progression. These include diffuse microglia/macrophage and T-cell infiltration, meningeal follicles, and smouldering, active lesions.
It’s also important to remember that treatment carries both risks and benefits and that DMTs can be detrimental in some cases. This is particularly true in the case of older, more disabled patients, such as many of those living with PMS.
DMTs increase the risk of severe infections including, in some cases COVID-19, said Marco, adding that discontinuation was safe.
No: Dr Kate Petheram
The NHS England Treatment Algorithm includes confirmed secondary progressive disease as a suggested DMT stopping criterion. However, this is not backed up by data and research, argued Dr Kate Petheram.
“When we don’t have prospective clinical trial data, we have to go back to the four pillars of medical ethics,” she said, explaining that these were autonomy, beneficence, non-maleficence, and justice.
There is evidence that ongoing DMTs can prevent worsening disability, and that stopping them has the potential to do harm, she explained.
One study, for example, found that people who discontinued injectable DMTs after long relapse-free period had a similar relapse rate as those who continued, but had a higher chance of disability progression. In addition, data from the Italian MS registry, published in 2020, found that even in late-onset MS, DMTs significantly reduced the risk of reaching EDSS 4.0.
It also made the point that the pivotal trials were not powered to assess the effect of treatment in the over 50s. “We cannot say they don’t work because the trials have not been done,” said Kate.
Importantly, she went on, clinicians do not agree on what secondary progressive MS is or how to define it. They cannot, then, identify non-active patients who should have their DMTs stopped.
Concluding, she said there was not enough data to support the discontinuation of DMTs in people with SPMS. “We have to wait for the evidence.”
References
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Hawker, K., O'Connor, P., Freedman, M. S., Calabresi, P. A., Antel, J., Simon, J., ... & OLYMPUS Trial Group. (2009). Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double‐blind placebo‐controlled multicenter trial. Annals of neurology, 66(4), 460-471. https://onlinelibrary.wiley.co...
Montalban, X., Hauser, S. L., Kappos, L., Arnold, D. L., Bar-Or, A., Comi, G., ... & Wolinsky, J. S. (2017). Ocrelizumab versus placebo in primary progressive multiple sclerosis. New England Journal of Medicine, 376(3), 209-220. https://www.nejm.org/doi/full/...
Kappos, L., Bar-Or, A., Cree, B. A., Fox, R. J., Giovannoni, G., Gold, R., ... & Kaida, K. (2018). Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. The Lancet, 391(10127), 1263-1273. https://pubmed.ncbi.nlm.nih.go...
This activity has been supported by sponsorship from Roche Products Ltd, Biogen Idec Ltd and Janssen-Cilag Ltd. The sponsors have had no control over the educational content of this activity.
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