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Multiple Sclerosis Progression and Relapse Activity in Children
Pietro Iaffaldano1, Emilio Portaccio2, Giuseppe Lucisano1,3
1Department of Translational Biomedicines and Neurosciences, University of Bari Aldo Moro, Bari, Italy.
Insights
Pediatric-onset multiple sclerosis (MS) patients show lower progression independent of relapse activity (PIRA) rates compared to adults. Early disease-modifying therapy (DMT) initiation is crucial for reducing both PIRA and relapse-associated worsening (RAW) in all MS patients.
Area of Science:
- Neurology
- Immunology
- Clinical Research
Background:
- Pediatric-onset multiple sclerosis (POMS) accounts for up to 20% of MS cases, with potential for greater repair capacity.
- Previous assumptions suggested POMS patients were protected against long-term disability.
Purpose of the Study:
- To compare the incidence of progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in POMS versus adult-onset MS (AOMS) and late-onset MS (LOMS).
- To identify factors associated with PIRA and RAW in different MS onset groups.
Main Methods:
- A cohort study utilizing prospectively acquired data from the Italian MS Register (June 2000 - September 2021).
- Analysis of longitudinal data from 16,130 patients with MS, comparing POMS, AOMS, and LOMS.
- Assessment of clinical and MRI features, disease-modifying therapy (DMT) exposure, and time to first DMT.
Main Results:
- Patients with POMS exhibited less disability, more active disease, and longer DMT exposure compared to AOMS and LOMS.
- The cumulative incidence of PIRA was lower in POMS (40.4%) compared to AOMS (44.3%) and LOMS (56.8%).
- Older age at onset, longer disease duration, and shorter DMT exposure were associated with higher PIRA risk. Delayed DMT initiation increased the risk of both PIRA and RAW.
Conclusions:
- While POMS patients are less likely to exhibit PIRA over a decade, pediatric onset does not fully protect against disease progression.
- These findings underscore the importance of early DMT initiation for all MS patients to mitigate both PIRA and RAW.
- DMT initiation was associated with a reduced occurrence of PIRA and RAW, irrespective of age at onset.
Importance:
Although up to 20% of patients with multiple sclerosis (MS) experience onset before 18 years of age, it has been suggested that people with pediatric-onset MS (POMS) are protected against disability because of greater capacity for repair.
Objective:
To assess the incidence of and factors associated with progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in POMS compared with typical adult-onset MS (AOMS) and late-onset MS (LOMS).
Design, Setting, And Participants:
This cohort study on prospectively acquired data from the Italian MS Register was performed from June 1, 2000, to September 30, 2021. At the time of data extraction, longitudinal data from 73 564 patients from 120 MS centers were available in the register.
Main Outcomes And Measures:
The main outcomes included age-related cumulative incidence and adjusted hazard ratios (HRs) for PIRA and RAW and associated factors.
Exposures:
Clinical and magnetic resonance imaging features, time receiving disease-modifying therapy (DMT), and time to first DMT.
Results:
After applying the inclusion and exclusion criteria, the study assessed 16 130 patients with MS (median [IQR] age at onset, 28.7 [22.8-36.2 years]; 68.3% female). Compared with AOMS and LOMS, patients with POMS had less disability, exhibited more active disease, and were exposed to DMT for a longer period. A first 48-week-confirmed PIRA occurred in 7176 patients (44.5%): 558 patients with POMS (40.4%), 6258 patients with AOMS (44.3%), and 360 patients with LOMS (56.8%) (P < .001). Factors associated with PIRA were older age at onset (AOMS vs POMS HR, 1.42; 95% CI, 1.30-1.55; LOMS vs POMS HR, 2.98; 95% CI, 2.60-3.41; P < .001), longer disease duration (HR, 1.04; 95% CI, 1.04-1.05; P < .001), and shorter DMT exposure (HR, 0.69; 95% CI, 0.64-0.74; P < .001). The incidence of PIRA was 1.3% at 20 years of age, but it rapidly increased approximately 7 times between 21 and 30 years of age (9.0%) and nearly doubled for each age decade from 40 to 70 years (21.6% at 40 years, 39.0% at 50 years, 61.0% at 60 years, and 78.7% at 70 years). The cumulative incidence of RAW events followed a similar trend from 20 to 60 years (0.5% at 20 years, 3.5% at 30 years, 7.8% at 40 years, 14.4% at 50 years, and 24.1% at 60 years); no further increase was found at 70 years (27.7%). Delayed DMT initiation was associated with higher risk of PIRA (HR, 1.16; 95% CI, 1.00-1.34; P = .04) and RAW (HR, 1.75; 95% CI, 1.28-2.39; P = .001).
Conclusions And Relevance:
PIRA can occur at any age, and although pediatric onset is not fully protective against progression, this study's findings suggest that patients with pediatric onset are less likely to exhibit PIRA over a decade of follow-up. However, these data also reinforce the benefit for DMT initiation in patients with POMS, as treatment was associated with reduced occurrence of both PIRA and RAW regardless of age at onset.
