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- Title
Multiple Sclerosis Progression and Relapse Activity in Children.
- Authors
Iaffaldano, Pietro; Portaccio, Emilio; Lucisano, Giuseppe; Simone, Marta; Manni, Alessia; Guerra, Tommaso; Paolicelli, Damiano; Betti, Matteo; De Meo, Ermelinda; Pastò, Luisa; Razzolini, Lorenzo; Rocca, Maria A.; Ferrè, Laura; Brescia Morra, Vincenzo; Patti, Francesco; Zaffaroni, Mauro; Gasperini, Claudio; De Luca, Giovanna; Ferraro, Diana; Granella, Franco
- Abstract
Key Points: Question: What proportion of disability worsening happens in conjunction with relapses vs independent of relapse activity in pediatric-onset multiple sclerosis (POMS), and how does this differ from adult-onset disease? Findings: This multicenter cohort study of 16 130 patients with MS found that although progression independent of relapse activity (PIRA) was rarely detectable before 18 years of age, pediatric onset was not protective against PIRA. Progression independent of relapse was observed in 40.4% of patients with POMS even while they were still young (ie, approximately a single decade of follow-up), and delay in disease-modifying therapy initiation and less time receiving therapy were both associated with a higher risk of PIRA in POMS. Meaning: This study suggests that POMS is not protective against disability worsening even in the absence of relapses. This cohort study assesses the occurrence of progression independent of relapse activity and relapse-associated worsening in pediatric and adult patients with multiple sclerosis. 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.
- Publication
JAMA Neurology, 2024, Vol 81, Issue 1, p50
- ISSN
2168-6149
- Publication type
Article
- DOI
10.1001/jamaneurol.2023.4455