Gender, age at PPMS onset has no impact on disability progression

Gender and age at the onset of disease don’t seem to have a clinically relevant impact on disability progression in people with primary progressive multiple sclerosis (PPMS), according to a recent study in Argentina.

Disease progression, based on the Expanded Disability Status Scale (EDSS) standardized measure of functional disability, was analyzed in patients who were between the age of 20 and 50 at disease onset over 10 years. The study, “Clinical impact of gender and age at onset on disease trajectory in primary progressive multiple sclerosis patients,” was published in the Multiple Sclerosis Journal.

In MS, the immune system attacks and destroys the myelin sheath, a protective coating around nerve fibers that helps them transmit signals efficiently, leading to nerve fiber degeneration and a range of MS symptoms. In PPMS, which accounts for about 15% of all MS cases, symptoms gradually worsen over time, without periods of remission where they remain stable.

Several factors have been identified as possible indicators for disease course and outcomes, including age and gender. In relapsing-remitting MS (RRMS), men have been shown to have a worse disease course and more severe disability than women. RRMS is the most common MS type, defined by relapses followed by periods of remission when symptoms ease.

However, “the current understanding remains inconclusive as to whether gender and age at onset play a significant role in influencing the progression of disability in patients with PPMS,” wrote the researchers, who studied 125 people with a confirmed diagnosis to investigate their impact at the onset of PPMS on the progression of disease disability. Slightly more than half the patients were women and they had an average of four visits with recorded EDSS per patient, for a total of 464 evaluations.

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The participants’ clinical data was obtained from the “RelevarEM” registry, an observational database that captures information on MS and neuromyelitis optica spectrum disorder in Argentina.

The men were older at disease onset than women (mean, 45.1 vs. 42.6) and had a longer disease duration (mean, 12.8 vs. 10 years). Significantly more women were treated with Ocrevus (ocrelizumab) than men (38% vs. 23%), but no differences were observed on the time to treatment since disease onset or treatment duration.

At the first, or baseline, evaluation, men and women had similar mean EDSS scores, but men had a higher score at the last evaluation (6.4 vs. 6). There were no significant differences between genders in the annual increase of disability, between one and 10 years after PPMS onset, however.

“These findings suggest that gender does not have a modifying effect on the disease trajectory in patients once the progressive phase starts,” the researchers wrote.

Regarding the age at disease onset, there were no differences in the rate of disease progression between patients with a 10- or 20-year difference in age at onset, up to 10 years of disease duration.

There was a trend for a faster decline in disability rate in older patients at progressive onset compared to younger ones, a phenomenon the researchers attributed to the progressive decline in immune function as people age, called immunosenescence.

Finally, for a difference in 20 years in age at onset, there were no clinically relevant differences in disease disability between men and women.

“In conclusion, we didn’t find clinically relevant differences in PPMS patients’ disability trajectories related to gender nor age at onset, after 10 years of disease and within this age span,” wrote the researchers, who said further research should consider clinically relevant measures that are not captured by the EDSS score, or over longer disease progression periods, although in older patients there might be cofounding factors related with natural aging.