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Original Investigation
May 3, 2021

Risk of Persistent Disability in Patients With Pediatric-Onset Multiple Sclerosis

Author Affiliations
  • 1Multiple Sclerosis Center, Gallarate Hospital, ASST Valle Olona, Gallarate (VA), Italy
  • 2Child Neuropsychiatry Unit, Department of Biomedical Sciences and Oncology, University of Bari “Aldo Moro,” Bari, Italy
  • 3Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro,” Bari, Italy
  • 4Multiple Sclerosis Clinical Care and Research Center, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Naples, Italy
  • 5Department of Neurology and Neurophysiology, MS Center, and Neuroimaging Research Unit, Vita-Salute San Raffaele University and San Raffaele Scientific Institute, Milan, Italy
  • 6Department of Neurology and Neurorehabilitation, IRCCS San Raffaele Scientific Institute, Milan, Italy
  • 7Policlinico Catania, Department of Medical, Surgery Science and Advanced Technology “GF Ingrassia,” Section of Neurosciences, MS Center, University of Catania, Catania, Italy
  • 8Department of Medical Science and Public Health, University of Cagliari and Multiple Sclerosis Center, Cagliari, Italy
  • 9Department of Biomedicine, Neurosciences, and advanced Diagnostic, University of Palermo, Palermo, Italy
  • 10Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy
  • 11Ospedale Policlinico San Martino-IRCCS, Genoa, Italy
  • 12Institute of Experimental Neurology and Multiple Sclerosis Center IRCCS, San Raffaele Hospital, Milan, Italy
JAMA Neurol. 2021;78(6):726-735. doi:10.1001/jamaneurol.2021.1008
Key Points

Question  Has the risk of developing a persistent disability improved over time in pediatric-onset multiple sclerosis (MS) in relation to changes in MS therapeutic and management standards?

Findings  In this study analyzing more than 3000 patients with pediatric-onset MS, there was a 50% to 70% reduction of the risk of reaching a persistent disability in later diagnosis epochs, paralleled by a greater and longer use of disease-modifying therapies, especially of high-potency drugs. Demographics and clinical disease activity at onset did not change significantly over time.

Meaning  An increase of approved disease-modifying therapies before age 18 years and a continuous upgrade in therapeutic management will further improve the prognosis of patients with pediatric-onset MS.

Abstract

Importance  Availability of new disease-modifying therapies (DMTs) and changes of therapeutic paradigms have led to a general improvement of multiple sclerosis (MS) prognosis in adults. It is still unclear whether this improvement also involves patients with pediatric-onset MS (POMS), whose early management is more challenging.

Objective  To evaluate changes in the prognosis of POMS over time in association with changes in therapeutic and managing standards.

Design, Setting, and Participants  Retrospective, multicenter, observational study. Data were extracted and collected in May 2019 from the Italian MS Registry, a digital database including more than 59 000 patients. Inclusion criteria were MS onset before age 18 years, diagnosis before January 2014, and disease duration of at least 3 years. Exclusion criteria were primary progressive MS, Expanded Disability Status Scale (EDSS) score of at least 8 one year after onset, unavailability of diagnosis date, and less than 2 EDSS score evaluations. Eligible patients were 4704 patients with POMS. According to these criteria, we enrolled 3198 patients, excluding 1506.

Exposures  We compared time to reach disability milestones by epoch of MS diagnosis (<1993, 1993-1999, 2000-2006, and 2007-2013), adjusting for possible confounders linked to EDSS evaluations and clinical disease activity. We then analyzed the difference among the 4 diagnosis epochs regarding demographic characteristics, clinical disease activity at onset, and DMTs management.

Main Outcomes and Measures  Disability milestones were EDSS score 4.0 and 6.0, confirmed in the following clinical evaluation and in the last available visit.

Results  We enrolled 3198 patients with POMS (mean age at onset, 15.2 years; 69% female; median time to diagnosis, 3.2 years; annualized relapse rate in first 1 and 3 years, 1.3 and 0.6, respectively), with a mean (SD) follow-up of 21.8 (11.7) years. Median survival times to reach EDSS score of 4.0 and 6.0 were 31.7 and 40.5 years. The cumulative risk of reaching disability milestones gradually decreased over time, both for EDSS score of 4.0 (hazard ratio [HR], 0.70; 95% CI, 0.58-0.83 in 1993-1999; HR, 0.48; 95% CI, 0.38-0.60 in 2000-2006; and HR, 0.44; 95% CI, 0.32-0.59 in 2007-2013) and 6.0 (HR, 0.72; 95% CI, 0.57-0.90; HR, 0.44; 95% CI, 0.33-0.60; and HR, 0.30; 0.20-0.46). In later diagnosis epochs, a greater number of patients with POMS were treated with DMTs, especially high-potency drugs, that were given earlier and for a longer period. Demographic characteristics and clinical disease activity at onset did not change significantly over time.

Conclusions and Relevance  In POMS, the risk of persistent disability has been reduced by 50% to 70% in recent diagnosis epochs, probably owing to improvement in therapeutic and managing standards.

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