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A recently published cohort study using data from an Italian multiple sclerosis (MS) register revealed a downward trend in the number of patients converting from onset to secondary progression (SP), partially explained by improvements in therapeutic coverage. Investigators concluded that these findings could inform clinical algorithms and health policy development, underscoring the imperative for continued therapeutic innovation in MS management.¹

The study, which aimed to characterize the MS disease course from onset to SP, included 9958 patients from 1993 to 2018, 1364 (13.7%) of which converted to SP. Five eras were established, each lasting 5 years, except for the second era, which was extended to 6 years to ensure a more homogenous distribution following the approval of highly effective disease-modifying therapies (DMTs).

Led by Emanuele D’Amico, MD, PhD, a medical doctor at the University of Catania, SPMS conversion was defined as a 3-strata progression magnitude with a minimum Expanded Disability Scale Score (EDSS) of 4.0 and a minimal pyramidal FS score of 2.0 at the time of conversion to SPMS confirmed at 3 months and at the end of follow-up (last EDSS score ≥4.0; last FS pyramidal score ≥2). In order to reduce the impact of transient EDSS modification due to relapses, all the EDSS scores collected during a relapse (+30 days) were excluded.

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The overall SP incidence rate was 1.26 (95% CI, 1.19-1.32), with rates showing a downward trend as each era passes (1^st era: 1.98 [95% CI, 1.73-2.27]; 5^th era: 1.15 [95% CI, 0.97-1.35]). Using multivariable Cox models, investigators found that the risk of SP conversion was lower in era 2 (HR, 0.78, 95% CI 0.66-0.93), in era 3 (HR, 0.63, 95% CI 0.52-0.76), in era 4 (HR, 0.57, 95% CI 0.46-0.70) and in era V (HR, 0.65, 95% CI 0.50-0.83) relative to the first era. When the multivariable model included the treatment coverage, a 10% increase was associated to a 19% lower risk of converting to SP.

Conversion to an SP form occurred after a mean time of 8.5 years (SD, 5.5), with converted patients showing an older mean age at onset (36.6 [SD, 10.3] vs 32.7 [SD, 9.5]) and higher baseline EDSS (2.0 vs 1.5) than non-converting patients. Furthermore, Patients who converted to SP had a higher rate of no prior DMT exposure (9.9% vs 5.2%) and lower overall treatment coverage (58.4 ± 31.5 vs 73.6 ± 27.6) compared to non-converting patients. Additionally, time to first treatment was longer in patients converting to SP (1.9 [SD, 2.3]) than non-converting ones (1.6 [SD, 2.4]).

In the 5^th disease onset era, investigators observed a significant improvement of 10-year longitudinal trajectories of EDSS in the non-converting patients (P for interaction = 0.0117). Conversely, in converting to SP patients, there was no difference in 10 year longitudinal trajectories between disease onset era (P for interaction = 0.4723). In non-converting patients, 10-year MSSS trajectories declined more in recent onset eras (P = 0.0035), whereas in SP-converting patients, MSSS increased over time without significant variation across onset eras (P = 0.7096).

D’Amico et al concluded that, “This 30-year analysis suggests that SPMS conversion rates have decreased over time, partially explained by improvements in therapeutic coverage and earlier treatment initiation. However, our findings suggest that DMT utilization alone cannot fully account for these changes. 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.”

REFERENCE
1. Zanghi A, Copetti M, Avolio C, et al. Multiple sclerosis from onset to secondary progression: a 30-year Italian register study. Neurol, Neurosurg, & Psych. Published June 15, 2025. doi:10.1136/jnnp-2025-335958