Risk for permanent disability decreases in pediatric-onset MS as treatments improve

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Disclosures:
Baroncini reports that he has received travel grants and fees for consultancy / speaking / scientific publications from Almirall, Biogen, Merck, Novartis, Roche, Sanofi Genzyme and Teva. See the study for all relevant financial disclosures from other authors.

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The risk of permanent disability in childhood MS decreased by 50% to 70% in an analysis of four diagnostic time points from 1993, likely due to improvements in treatment standards, according to results published in JAMA Neurology.

“The availability of new disease-modifying therapies and changes in therapeutic paradigms have led to an overall improvement in MS prognosis in adults. It is still unclear whether this improvement also affects patients with pediatric MS, for whom early treatment is more challenging, ” Damiano Baroncini, MD, of the Multiple Sclerosis Center at Gallarate Hospital in Italy, and colleagues wrote.

In this retrospective, multicentre, observational study, Baroncini and colleagues pooled data from the Italian MS registry of 3,198 patients (mean age at onset of MS, 15.2 years; 69% female; median time to diagnosis, 3.2 years) to assess changes in the prognosis of MS in children in relation to changes in therapeutic and management standards.

Researchers grouped patients according to four MS diagnosis times – before 1993 (n = 619), between 1993 and 1999 (n = 785), 2000 to 2006 (n = 934), and 2007 to 2013 (n = 860) – and adjusted for possible confounding factors related to assessments of the Expanded Disability Status Scale (EDSS) and clinical disease activity. They then assessed the differences in demographics, clinical disease activity at onset, and disease-modifying therapies between the four diagnosis times.

Disability milestones included EDSS scores of 4 and 6, confirmed at the next clinical evaluation and at the last available office visit. According to the study results, the mean follow-up was 21.8 years.

Findings by Baroncini and colleagues showed that the median survival times to reach an EDSS score of 4 was 31.7 years, compared to 40.5 years to reach an EDSS score of 6.

Researchers saw a gradual decrease in the cumulative risk of reaching disability milestones for an EDSS score of 4 over time (HR = 0.70; 95% CI, 0.58-0.83 during 1993 to 1999; HR = 0.48; 95% CI, 0.38-0.6 during 2000 to 2006; HR = 0.44; 95% CI, 0.32-0.59 during 2007 to 2013) and a score of 6 (HR = 0.72; 95% CI, 0.57-0.9 for 1993 to 1999; HR = 0.44; 95% CI, 0.33-0.6 for 2000 to 2006; HR = 0. 3; 95% CI, 0.2-0.46 during 2007 to 2013).

Baroncini and colleagues found that more patients diagnosed with childhood MS underwent treatment with disease-modifying therapies – especially potent drugs – given earlier and for longer durations. The percentage of patients who started treatment with disease-modifying therapies during a pediatric age was 6% before 1993, 11% between 1993 and 1999, 26% between 2000 and 2006, and 39% between 2007 and 2013 (P <.001).

However, clinical disease activity at onset and demographics did not appear to change significantly over time, researchers noted.

Limitations of the study included a lack of MRI data and cognitive assessment, as well as recall bias due to the retrospective design of the study and legal censoring, the latter being “particularly evident” in the subgroup of patients with a pediatric diagnosis.

“In this study analyzing more than 3,000 patients with pediatric MS, there was a 50% to 70% reduction in the risk of achieving persistent disability in later periods of diagnosis, in parallel with greater and longer use of disease-modifying therapies , especially from potent drugs, ”wrote Baroncini and colleagues. “An increase in approved disease-modifying therapies before the age of 18 and continued improvement in therapeutic treatment will further improve the prognosis of patients with childhood MS.”

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