Older Age Is Associated with a First Clinical Demyelinating Event in Children with the Radiologically Isolated Syndrome (2671)

Objective: To determine whether age at index scan is associated with the subsequent development of a first clinical demyelinating event in children with the radiologically isolated syndrome (RIS). Background: The typical MRI findings of multiple sclerosis (MS) may be detected incidentally in individuals who underwent MRI scans for unrelated reasons. This clinical scenario has been termed RIS. We previously reported that 42% of children with RIS developed a first clinical demyelinating event in a median of 2 years. Little is known about risk factors associated with the development of a first clinical demyelinating event. Design/Methods: We analyzed a historical cohort of children (≤18 years) with RIS enrolled in an international longitudinal study. All children met 2010 MRI criteria for dissemination in space (DIS) on index scans (Ped-RIS). All scans also met 2017 DIS criteria on MRI. We created multivariable Cox proportional hazards models for time to a first clinical demyelinating event. Results: We included 89 children with Ped-RIS (median follow-up time 2.8 years; interquartile range 1.7–5.1 years). Median age at index scan was 15.4 years (range 8.1–17.9 years) and 68% of children were girls. Older age at index scan was associated with increased risk of a first clinical demyelinating event even after adjustment for sex, ≥2 unique oligoclonal bands in spinal fluid, asymptomatic spinal cord lesions on MRI, and treatment with a disease-modifying agent for MS (hazard ratio [HR] 1.4 per one year increase, 95% C.I. 1.04–1.40, p=0.04). Children ≥13 years (n=72, 81%) were at increased risk compared to those <13 years (adjusted HR 2.9, 95% C.I. 1.01–9.20, p=0.04). Conclusions: Older children with Ped-RIS, particularly those ≥13 years, are at increased risk for a first clinical demyelinating event. This information is important for parental counseling, consideration of more frequent monitoring, and identifying children at highest risk who may benefit from enrollment in an intervention trial. Disclosure: Dr. Makhani has nothing to disclose. Dr. Lebrun-Frenay has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting fees, honoraria or scientific committee support: Bayer Schering, Biogen, Genzyme, Merck Serono, Novartis, Teva. Dr. Siva has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck, Novartis, Teva, Genzyme, Bayer, Roche, Biogen Idec/Gen Ilac-Turkey.Dr. Wassmer has nothing to disclose. Dr. Narula has nothing to disclose. Dr. Mar has nothing to disclose. Dr. Santoro has nothing to disclose. Dr. Ahsan has nothing to disclose. Dr. Tenembaum has nothing to disclose. Dr. Brenton has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis.Dr. Cabre has nothing to disclose. Dr. Carra-Dalliere has nothing to disclose. Dr. Ciron has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck%2C%20Roche%2C%20Biogen%2C%20Novartis%2C%20Teva. Dr. De Seze has nothing to disclose. Dr. Deiva has nothing to disclose. Dr. Durand Dubief has nothing to disclose. Dr. Inglese has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis Pharmaceuticals, National Multiple Sclerosis Society, Noto Foundation, NIH, and Teva Neuroscience.Dr. Langille has nothing to disclose. Dr. Mathey has nothing to disclose. Dr. Neuteboom has nothing to disclose. Dr. Palavra has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Sanofi-Genzyme, Merck, Novartis and Teva Pharmaceuticals. Dr. Palavra has received research support from Biogen. Dr. Pelletier has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jean Pelletier has received compensation for consulting services and speaking honoraria from Biogen, Roche, MedDay, Sanofi-Genzyme, Merck, Novartis and Teva Pharmaceuticals. Dr. Pelletier has received research support from Jean Pelletier received a research grant from Biogen, Roche and Merck. Dr. Pohl has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting and speaker’s honoraria and support for attending conferences from Novartis Pharma AG, Forward Pharma, Biogen-Idec, Merck-Serono, Teva and Eisei. Dr. Reich has received research support from Vertex.Dr. Rojas has nothing to disclose. Dr. Shabanova has nothing to disclose. Dr. Shapiro has nothing to disclose. Dr. Thompson-Stone has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Homer and Conway, P.C. Dr. Thouvenot has nothing to disclose. Dr. Tinore has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Biogen-Idec, Genzyme, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio and Teva Pharmaceuticals. Dr. Tinore has received personal compensation in an editorial capacity for co-editor of Multiple Sclerosis Journal-ETC. Dr. Tinore has received research support from Biogen-Idec, Genzyme, Merck-Serono, Novartis. Dr. Uygunoglu has nothing to disclose. Dr. Vargas has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals, Biogen, Octapharma. Dr. Vargas has received research support from Teva Pharmaceuticals. Dr. Venkateswaran has nothing to disclose. Dr. Verhelst has nothing to disclose. Dr. Vermersch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi, Servier, and Teva. Dr. Vermersch has received research support from Almirall, Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi, Servier, and Teva.Dr. Azevedo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi-Genzyme, Genentech, EMD Serono, and Alexion Pharmaceuticals.Dr. Kantarci has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis and Biogen. Dr. Kantarci has received research support from Biogen, the Multiple Sclerosis Society, the Mayo Foundation, and the Hilton Foundation. Dr. Okuda has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acorda Therapeutics, Genentech, Genzyme, Teva, consulted for Bayer, EMD Serono, Genzyme, Novartis, served on the speakers’ bureau for Acorda Therapeutics. Dr. Okuda has received research support from Biogen. Dr. Pelletier has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, EMD Serono, Novartis, Roche, and Sanofi-Genzyme. Dr. Pelletier has received research support from Biogen, EMD Serono, Novartis, Roche, and Sanofi-Genzyme. Dr. (OFSEP) has nothing to disclose. Dr. (SFSEP) has nothing to disclose. Dr. (RISC) has nothing to disclose. Dr. Consortium (PARIS) has nothing to disclose.

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