By Lucy Piper, medwireNews Reporter
medwireNews: Progression of multiple sclerosis (MS) in the absence of relapses can occur at any age, although it is less common in children than adults with the condition, suggests research.
“The important inference from our findings is that, although patients with MS who are younger than 18 years have a lower rate of disability, paediatric age itself is not protective”, say Maria Trojano (University of Bari, Italy) and colleagues in JAMA Neurology.
“In other words, the time of injury itself is not protective against disability; rather, while the subject has a youthful immune system and a more resilient brain, less disability is manifest.”
The team prospectively studied data from the Italian MS register on 16,130 patients (68.3% women) who had a clinically isolated syndrome and relapsing–remitting disease course, with three or more evaluations over at least 5 years of follow-up. Of these, 1383 (8.6%) had paediatric onset, 14,113 (87.5%) had adult onset and 634 (3.9%) had late onset. The median ages of MS onset for the three groups were 15.8 years, 29.3 years and 52.4 years, respectively.
At baseline, patients with paediatric-onset MS had a significantly longer median disease duration than their adult- and late-onset peers (5.59 vs 2.72 and 1.68 years, respectively). A significantly greater proportion of the paediatric-onset patients had also experienced at least two relapses between onset and the first clinic visit (40.9 vs 31.9 and 17.0%) and they had spent a significantly greater percentage of time with exposure to disease-modifying therapies (DMTs; 87.4 vs 85.7 and 82.2%).
A first 48-week confirmed disability accrual event that was not associated with relapse activity occurred in 7176 (44.5%) patients. This was defined as an increase from baseline in Expanded Disability Status Scale score of at least 1.5 points for a baseline score of 0, at least 1.0 point for a baseline score of 1.0–5.5, and more than 0.5 points for a baseline score of 6.0 point or above.
The rate among patients with paediatric-onset MS was 40.4%, which was significantly lower than that for patients with adult-onset or late-onset MS, at respective rates of 44.3% and 56.8%.
Factors significantly associated with an increased risk of progression independent of relapse activity were older age at onset, with hazard ratios (HRs) of 1.42 for adult-onset MS and 2.98 for late-onset MS versus paediatric onset, and a longer disease duration (HR=1.04).
By contrast, a higher percentage of DMT exposure protected against progression not related to relapse activity, with an HR of 0.69. A finding that the researchers say, “suggests that pathogenic mechanisms underlying [progression independent of relapse activity] can be, at least in part, modified by currently approved DMTs.”
To look at progression rates as a function of age, the team selected a subgroup of 3777 patients who had a first visit within a year of disease onset and were monitored regularly every 6 months.
A total of 842 confirmed disability accrual events independent of relapse activity occurred in this group, and Trojano and colleagues report that they were “rare in childhood”, starting around age 18–20 years.
Indeed, they found that the cumulative incidence of such events according to age was 1.3% at 20 years of age, after which it increased rapidly to 9.0% between 21 and 30 years of age, and then nearly doubled each decade between 40 (21.6%) and 70 years of age (78.7%).
A similar trend was seen for relapse-related progression, with rates of 0.5% at 20 years, 7.8% at 40 years and 24.1% at 60 years. However, there was no further increase at 70 years (27.7%).
The researchers also highlight that the risk of progression was significantly increased if DMT initiation was delayed beyond 6 months after disease onset compared with before, by 16% for progression independent of relapse activity and by 75% for progression associated with relapse. This was irrespective of age.
Trojano and colleagues conclude that as MS progression independent of relapse activity “can predict worse long-term prognosis and is partially preventable by DMT, early diagnosis and treatment represent the cornerstones of MS management.”
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JAMA Neurol 2023; doi:10.1001/jamaneurol.2023.4455