Menarche and Relapses in Girls with Pediatric Multiple Sclerosis (1270)

Objective: To evaluate the association between menarche and disease course in pediatric multiple sclerosis (MS) through comparison of relapse rates across the pre-menarche, peri-menarche, and post-menarche periods. Background: Sex steroid hormones have a clinical impact on the immune system. Puberty may be a trigger for MS disease activity, with mean age of pediatric MS onset occurring near age 13 years. Design/Methods: This is a retrospective analysis of a prospectively followed cohort of girls meeting MS criteria within the US Network of Pediatric MS Centers database. Only individuals with known menarche dates were included in the analysis. Relapses were collected prospectively. Both negative binomial and repeated Cox regression models were used to assess the association of pubertal development stage with relapse rate, adjusted for tier of disease-modifying therapy (DMT) and body mass index (BMI). Results: Of the 504 girls included, onset was during pre-menarche in 53, peri-menarche in 84 (within +/− 1 year of menarche), and post-menarche in 367. The median time of MS onset was 2.5 years after menarche. In negative binomial adjusted analysis, relapse rate during the pre-menarche period was 0.44, peri-menarche period was 0.50, and post-menarche period was 0.36 (p=0.15). In adjusted repeated Cox regression analysis, there was a trend for increasing relapse rates with stage of development from pre-menarche through menarche (pre-menarche HR 0.60 (95% CI 0.39 to 0.92) and peri-menarche HR 0.79 (95% CI 0.58 to 1.08) compared to reference of post-menarche, p=0.049). Conclusions: Before menarche girls have lower relapse rates. Onset of puberty may be a time of increase in disease activity and may require consideration of a change in therapeutic approach. Disclosure: Dr. Krysko has received research support from MS fellowship grant from NMSS; MS fellowship grant from Biogen.Dr. Waltz has nothing to disclose. Dr. Chitnis has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, Sanofi-Genzyme, Roche, and Genentech. Dr. Chitnis has received research support from Novartis, Octave Biosciences, Mallinckrodt, and Verily Life Sciences.Dr. Weinstock-Guttman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, , Novartis, Genentech, EMD Serono, Abbvie, Mallickrodt, Bristol Myers.. Dr. Weinstock-Guttman has received research support from Biogen, Novartis, Genentech, and EMD Serono..Dr. Aaen has received research support from Biogen.Dr. Benson has received research support from She has received funding for research unrelated to this work for a Biogen sponsored clinical trial..Dr. Harris 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.Dr. Lotze has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with He has served as a consultant/speaker for Biogen.. Dr. Lotze has received research support from PTC Therapeutics, Serepta Therapeutics and Catalyst Therapeutics. Dr. Mar has nothing to disclose. Dr. Ness has received research support from Chugai-Roche.. Dr. Rensel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory Board or panel: Serono, Biogen. Consultant: Biogen, Teva, Genzyme and Novartis. Speaker9s Bureau: Novartis, Genzyme, Biogen, Multiple Sclerosis Association of America.. Dr. Rensel has received research support from Grants/Research support: She has received commercial research support from Medimmune, Novartis, Biogen (MS Paths) and Genentech. She has received foundation/society research support from the National Multiple Sclerosis Society. She has received educationa. Dr. Rodriguez has nothing to disclose. Dr. Rose has received research support from AbbVie, Biogen, Teva, the Cumming Foundation, the National Institutes of Health, the National Multiple Sclerosis Society, and the US Department of Veterans Affairs. Dr. Rutatangwa has received research support from She is supported by a Biogen MS fellowship grant..Dr. Schreiner has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with ACI. Dr. Schreiner has received research support from ADAMAS. Dr. Waubant has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with EW has not received any pharmaceutical company honorarium. She is site PI for Novartis and Roche multicenter trials. She volunteers on an advisory board for a Novartis trial. She is a non-remunerated advisor for clinical trial design to Novartis, Biogen-I. Dr. Waubant has received research support from She has funding from the NMSS, PCORI and the Race to Erase MS. She receives compensation as the section editor for Annals of Clinical and Translational Neurology, and co-Chief editor for MSARD.Dr. Casper has nothing to disclose. Dr. Graves has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Genzyme, Novartis, and Celgene. Dr. Graves has received research support from the National MS Society, Race to Erase MS, UCSF CTSI RAP Program, Biogen, and Genentech.