Risk of Faster Progression in PPMS Tied to Older Age and Active Disease

Risk of Faster Progression in PPMS Tied to Older Age and Active Disease
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Older age at onset and evidence of active disease, like clinical relapses or inflammatory brain lesions, significantly increase the likelihood of  faster disability progression in primary progressive multiple sclerosis (PPMS), a natural history study suggests.

These findings — which included active disease being seen in 31% of the 178 patients in this study — may help in understanding factors that influence PPMS course, leading to clinical trials and therapeutic approaches better designed for this population, its researchers said.

Age-related data also support the existence of other underlying mechanisms of neurodegeneration apart from disease activity.

The study, “Disease activity impacts disability progression in primary progressive multiple sclerosis,” was published in the journal Multiple Sclerosis and Related Disorders.

PPMS is marked by a steady disease progression from the onset of symptoms, but the rate of progression varies among patients. Whether disease activity in PPMS significantly contributes to the pace of progression remains controversial.

This disease is classified as “active” when a patient has an occasional relapse, or there is evidence of new brain lesions on a magnetic resonance imaging (MRI) scan.

In addition, “most natural history studies on MS patients have been performed in Western Europe and North America, none of which included Latin American patients,” the researchers wrote.

Researchers in Argentina set out to identify potential predictors of disability worsening, including disease activity, in 178 PPMS patients (95 women and 83 men) being followed at two MS clinics in Buenos Aires.

The team retrospectively analyzed demographic and clinical data for this group. Patients had a median age of 42 at disease onset — manifested as partial paralysis of both legs in 78% of the cases — and  were followed at the clinics for a median of four years (range, one month to nearly 20 years).

A total of 59 patients had at least two consecutive MRI scans available. The researchers noted that since most patients with relapses did not immediately undergo an MRI scan, the number of inflammatory brain lesions may have been underreported.

During follow-up, 56 of these patients (31%) showed signs of active disease, which, in 98% of the cases, was detected during the first five years after onset.

A total of 26 patients (14.6%) had at least one relapse, and new brain lesions were detected in 38 patients (21%). Eight (4%) showed both clinical relapses and new brain lesions.

Disability was assessed using the Expanded Disability Status Scale (EDSS); this scale ranges from 0 to 10, with higher scores indicating greater disability.

Time to reach disability milestones (EDSS scores of 4, 6, 7 and 8) from disease onset was also assessed. EDSS scores of 4 or higher reflect impaired mobility, and scores from 6 to 8 include needing a walking aid (score 6), being essentially restricted to a wheelchair (score 7), or restricted to a bed or chair, or a to wheelchair a person cannot move on their own (score 8).

Patients generally reached an EDSS score of 4 in five years, an EDSS score of 6 in seven years, of 7 in 10.5 years, and a score of 8 in 10 years, results showed.

Notably, those diagnosed later in life had a significantly higher risk of faster disease worsening. Specifically, every 10-year jump in age at onset raised the risk of reaching an EDSS score of 4 by 26%, and of 6 by 31%.

The presence of active disease also significantly associated with faster disease progression, as patients with reports of a relapse or new brain lesions showed greater disability, reaching EDSS scores of 6 or higher more quickly than those without signs of active disease.

Overall, the team concluded that “older age at onset and presence of clinical and/or radiological disease activity correlated with accelerated disability progression in this cohort of PPMS patients.”

The researchers noted that their findings on the largest PPMS case series from Latin America were consistent with results from previous studies.

Data support the existence of age-related processes contributing to neurodegeneration in PPMS, and suggest that the presence of relapses and new brain lesions may represent “additional active damage over the cumulative neurodegenerative process of the disease,” the researchers wrote.

They emphasized that while this study may help to better understand PPMS and improve clinical trial design, larger and prospective studies are needed to confirm these results.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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