Transition from RRMS to SPMS fell in recent years; challenges remain
Greater availability of DMTs doesn’t fully explain decrease in transition rates
The rates of people with multiple sclerosis (MS) who advance from a relapsing disease course to a secondary progressive one have decreased significantly in the past decades, a 30-year study in Italy shows.
While the greater availability and earlier use of disease-modifying therapies (DMTs) have played a role, this doesn’t fully explain the decrease in transition rates.
“Additional factors likely contribute to this evolution, including shifts in diagnostic criteria, more stringent definitions of disease progression, changes in patient selection and evolving clinical practices,” wrote the study’s researchers, who noted the interplay between all these factors “collectively shapes the observed disease trajectories.” They said “future research should adopt a multifaceted approach that considers both treatment strategies and these contextual factors to develop more comprehensive models of disease progression and more effective interventions for patients with MS.”
The study, “Multiple sclerosis from onset to secondary progression: a 30-year Italian register study,” was published in the Journal of Neurology, Neurosurgery and Psychiatry.
MS often starts with a relapsing-remitting course (RRMS), where periods of new or suddenly worsening symptoms, called relapses, are followed by periods of recovery, called remissions. Over time, patients may transition to secondary progressive MS (SPMS), symptoms steadily worsen, even in the absence of relapses.
DMTs can alter the course of MS, but how these treatments have impacted the long-term progression of the disease in the past decades, including the transition to secondary progressive MS, isn’t fully understood, leading researchers in Italy to draw on data from the Italian MS Register from 1993 to 2018. Patients with at least five years of follow-up were included and grouped into five eras, based on when their symptoms first appeared. Each era lasted five to six years.
Tracking declining rates of transition to SPMS
Of 9,958 adults diagnosed with MS, 13.7% transitioned from RRMS to SPMS over an average of 8.5 years. On average, these patients were older at the onset of their symptoms and had a longer delay before being prescribed DMTs (1.9 vs. 1.6 years).
They were also nearly twice as likely to have never received a DMT (9.9% vs. 5.2%) and had lower therapeutic coverage (58.4% vs. 73.6%), that is the percentage of disease duration during which they received DMTs.
The overall transition rate to SPMS was 1.26 per 100 person-years, declining from 1.98 in the earliest era of January 1993 to December 1997 to 1.15 in the most recent one from January 2014 to January 2018. A person-year is a unit that combines the number of people in a study with the length of time they were followed.
Statistical analyses showed that a 10% increase in treatment coverage was associated with a 19% reduced risk of transitioning to SPMS, even after adjusting for other factors. These data suggest the decrease in transition rates is “partially explained by improvements in therapeutic coverage,” the researchers wrote.
The time to first being prescribed a DMT decreased over time from a median 3.2 years in the earliest era to about seven months (0.6 years) in the most recent one, and this trend was seen in patients who transitioned and in those who didn’t.
Disability progressed significantly more slowly in recent eras for those who didn’t develop SPMS, but the patients who transitioned to SPMS showed similar progression across all eras.
While a transition to SPMS has become less frequent over time, progression remains an unmet need. A more integrated understanding of disease dynamics could inform both clinical decision making and therapeutic development.
Along with reinforcing the importance of early intervention and sustained access to DMTs, “these findings could inform clinical algorithms and health policy development, underscoring the imperative for continued therapeutic innovation in MS management,” the researchers wrote.
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