Early aggressive treatment to delay conversion to secondary progressive MS
medwireNews: The findings from two studies published in JAMA show the benefits of initial disease-modifying therapy (DMT) and nonmyeloablative haematopoietic stem cell transplantation (HSCT) in delaying conversion to secondary progressive multiple sclerosis (MS).
In the first observational cohort study, Thomas Kalincik (Royal Melbourne Hospital, Victoria, Australia) and colleagues found that initial treatment with fingolimod, alemtuzumab or natalizumab in patients with relapse-remitting MS was associated with a significant 34% reduction in the risk of converting to secondary progressive MS compared with initial glatiramer acetate or interferon beta treatment.
The time to sustained progression, based on an Expanded Disability Status Scale (EDSS) increase of 1 point for scores of 5.5 or below and 0.5 points for scores above 5.5 points and a final score of at least 4 points in the absence of relapse and that could be confirmed up to 3 months later, was compared across subsets of 1555 propensity-score matched patients who were either treated or untreated.
Initial treatment with glatiramer acetate or interferon beta was superior to no treatment, reducing the likelihood of conversion to secondary progressive MS by 29%, with 5-year absolute risks of 12% versus 27%.
The team also notes that the timing of treatment affected the risk of conversion, with a significant 23% reduction seen in patients initiating glatiramer acetate or interferon beta treatment within 5 years of treatment compared with later and a 24% reduction in patients escalating to finglimod, alemtuzumab or natalizumab within 5 years compared with later.
“These findings, considered along with the risks associated with these therapies, may help inform decisions regarding disease-modifying treatment selection for patients with relapsing-remitting MS”, the researchers conclude.
In the second study, HSCT was shown to be effective for patients with relapsing-remitting MS whose disease remained active despite DMT. Among 103 patients randomly assigned to HSCT or a different DMT deemed appropriate by a neurologist, three in the HSCT group experienced disease progression, defined as an EDSS score increase of at least 1.0 point on two evaluations 6 months apart, compared with 34 in the DMT group.
The median time to progression was 24 months among the DMT group and could not be calculated in the HSCT group due to too few events, giving a significant hazard ratio for progression of 0.07.
During the first year, average EDSS scores improved from 3.38 to 2.36 points in the HSCT group, whereas they worsened from 3.31 to 3.98 points in those continuing DMT, giving a significant between-group difference of 1.7 points.
Richard Burt (University Feinberg School of Medicine, Chicago, Illinois, USA) and colleagues note that HSCT was also superior in terms of fewer relapses, improved magnetic resonance imaging lesion volume, maintenance of no disease activity and better quality of life.
But they also highlight some important limitations of the trial, including patients whose DMT failed being able to cross over to receive HSCT and most notably exclusion of the DMTs alemtuzumab and oral cladribine, as well as ocrelizumab, which was not commercially available at the time of study between 2005 and 2016.
Indeed, Harold Atkins, from the University of Ottawa in Ontario, Canada, comments in a related editorial that “almost a third of patients in the DMT group were treated with a second first-line agent (glatiramer acetate or beta interferon)”.
He adds that there is also “concern among some treating physicians about the rigor of HSCT and the risks associated with the procedure”. And while there were no treatment-related deaths in the study, he believes “caution in patient selection remains warranted”.
Nevertheless Atkins concludes that “[e]ven with the limitations of the trial, the results support a role of HSCT delivered at centers that are experienced in the clinical care of patients with highly active MS”.
By Lucy Piper
medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group