Distribution and predictors of disease severity in pediatric multiple sclerosisInvestigate the distribution of disease severity in pediatric-onset multiple sclerosis (MS)

Objective: Investigate the distribution of disease severity in pediatric-onset multiple sclerosis (MS). Background: Previous studies indicate pediatric-onset MS has a slower progression to disability than adult-onset MS; however, these studies account for disability as measured by the EDSS scale, which focuses largely on locomotor deficits, which are less prominent in children. There is a need to better characterize disability distribution and accrual in this population. Design/Methods: Data collected prospectively by the U.S. Network of Pediatric MS Centers was reviewed. Patients were stratified by the number of years from first symptoms of MS to EDSS assessment and an MS severity score (MSSS) was calculated per Roxburgh et al. criteria. For each year, the lowest and highest EDSS scores were calculated and then normalized by dividing 1+the number of available assessments. Scores from +/− one year were used to avoid stochastic fluctuations. This value was then multiplied by 10 to provide a range from 0–10 (MSSS = (Rank Average/N+1) ×10). Pediatric MSSS scores represented percentiles amongst patients who had the disease for the same disease duration. Results: In total, 994 patients were reviewed, consisting of 4,349 unique data points. Range of disability in our pediatric cohort at one year from diagnosis was narrower than data published by Roxburgh et al., with EDSS of 0, 1, 1.5, and 2.0, corresponding to the 14th, 40th, 60th, and 76thpercentiles compared to adults (7th, 24th, 43rd, 59th). This pattern was maintained at 2, 5, and 10 year’s disease duration (2 years: 14th/5th, 42nd/20th, 64th/37th, and 80th/52nd; 5 years: 13th/3rd, 38th/13th, 60th/26th, and 78th/39th; 10 years: 14th/2nd, 38th/8th, 56nd/15th, and 72nd/21st). Conclusions: The distribution of disease severity by MSSS scoring in pediatric patients with MS is much more narrow than adults. This could have significant implications on clinical intervention analysis utilizing EDSS scoring alone. Disclosure: Dr. Santoro has nothing to disclose. Dr. Waltz has nothing to disclose. Dr. Casper has nothing to disclose. Dr. Chitnis has received personal compensation for advisory boards/consulting with F. Hoffman-La Roche, Biogen and Novartis. Dr Chitnis has received research support from Biogen, Merck Serono, Verily and Novartis. Dr. Aaen has received research support from Biogen. Dr. Belman has nothing to disclose. Dr. Benson has nothing to disclose. Dr. Candee has nothing to disclose. Dr. Gorman has received research support from Biogen. Dr. Goyal has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities as a neuroradiology consultant. Dr. Goyal holds stock and/or stock options in IBM. Dr. Graves has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Genentech, Inc. and S3 Group. Dr. Graves has received research support from Biogen and Genentech. Dr. Greenberg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Alexion, EMD Serono. Dr. Greenberg has received research support from Chugai, Medimmune, Genentech, MedDay, PCORI, NIH, NMSS and Guthy Jackson Charitable Foundation for NMO. Dr. Harris has nothing to disclose. Dr. Kahn has nothing to disclose. Dr. Krupp has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Everyday Health, Gerson Lehman, Novartis, RedHill Biopharma, Roche, Shire, and Sanofi-Aventis. Dr. Krupp has received royalty, license fees, or contractual rights payments from Biogen, Reata Pharma, AbbVie Pharmaceuticals, Amicus Therapeutics, SA Inventions, Finkhar Health, Janssen Pharmaceuticals, Eisai, IPSOS, Octapharma, Atara Biotherapeutics, Merck, Research Tech, and ERT Inc. Dr. Krupp has received research support from Biogen and Novartis Pharmaceuticals. Dr. Lotze has received research support from PTC Therapeutics, Serepta Therapeutics and Catalyst Therapeutics. Dr. Mar has nothing to disclose. Dr. Moodley has nothing to disclose. Dr. Ness has nothing to disclose. Dr. Rensel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Teva, Genzyme and Novartis. Dr. Rensel has received research support from Medimmune. Dr. Rodriguez has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with MedDay. Dr. Rose has received research support from the National Multiple Sclerosis Society, the Guthy Jackson Foundation, the Western Institute for Biomedical Research, Teva Neuroscience and Biogen. Dr. Rubin has nothing to disclose. Dr. Schreiner has received research support from Biogen and MSDx. Dr. Tillema has nothing to disclose. Dr. Waldman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UpToDate, Optum Inc. Dr. Waldman holds stock and/or stock options in Spark, Thermo Fisher, and Pfizer. Dr. Waldman has received research support from Ionis Pharmaceuticals. Dr. Waubant has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AAN for Frontiers in neurology talk, The Corpus for talks, compensation for editorial work for Annals of Clinical and Translational Neurology and MS and Related Disorders. Site PI for clinical trials with Roche, Biogen Idec and Novartis Dr. Weinstock-Guttman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, EMD Serono, Genentech, Novartis, Mallinckrodt, and Celgene. Dr. Weinstock-Guttman has received research support from Biogen Idec, Novartis, and Genentech.