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

Source/Disclosures

Disclosures:
Baroncini reports receiving travel grants and compensations for consulting/speaking/scientific publications activities from Almirall, Biogen, Merck, Novartis, Roche, Sanofi Genzyme and Teva. Please see the study for all other authors’ relevant financial disclosures.

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Risk for permanent disability in pediatric-onset MS decreased by 50% to 70% in an analysis of four diagnostic time points starting in 1993, likely due to improvements in treatment standards, according to results published in JAMA Neurology.

“Availability of new disease-modifying therapies and changes of therapeutic paradigms have led to a general improvement of MS prognosis in adults. It is still unclear whether this improvement also involves patients with pediatric-onset MS, whose early management is more challenging,” Damiano Baroncini, MD, of the Multiple Sclerosis Center at Gallarate Hospital in Italy, and colleagues wrote.

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

Researchers grouped patients according to four MS diagnosis time periods — 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 confounders associated with Expanded Disability Status Scale (EDSS) evaluations and clinical disease activity. They then assessed the differences in demographic characteristics, clinical disease activity at onset and disease-modifying therapies among the four diagnosis time periods.

Disability milestones included EDSS scores of 4 and 6 confirmed during the following clinical evaluation and during the last available office visit. Mean follow-up was 21.8 years, according to the study results.

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

Researchers observed a gradual decline in the cumulative risk for 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 during 1993 to 1999; HR = 0.44; 95% CI, 0.33-0.6 during 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 pediatric-onset MS during later time periods underwent treatment with disease-modifying therapies — specifically high-potency drugs — that were administered earlier and for longer durations. The percentage of patients beginning 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 demographic characteristics did not appear to significantly change throughout time, researchers noted.

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

“In this study analyzing more than 3,000 patients with pediatric-onset MS, there was a 50% to 70% reduction of the risk for reaching a persistent disability in later diagnosis epochs, paralleled by a greater and longer use of disease-modifying therapies, especially of high-potency drugs,” Baroncini and colleagues wrote. “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.”

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