Real-world Effectiveness of Initial Treatment with Newer versus Injectable Disease-modifying Therapies in Pediatric Multiple Sclerosis (625)

Objective: We assessed real-world effectiveness of initial treatment with newer compared to injectable disease-modifying therapies (DMT) on disease activity in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS).

Background: Treatment of pediatric MS is challenging as most DMTs lack randomized controlled trial data in children.

Design/Methods: This is a cohort study of children with MS/CIS followed at 12 clinics in the US Network of Pediatric MS Centers, who received initial therapy with newer (fingolimod, dimethyl fumarate, teriflunomide, natalizumab, rituximab, ocrelizumab) or injectable (interferon-beta or glatiramer acetate) DMTs. Propensity scores (PS) were computed with logistic regression to predict newer DMT use, including preidentified confounders. Relapse rate while on initial DMT was modeled with negative binomial regression, adjusted for PS-quintile. Time to new/enlarging T2 hyperintense and gadolinium-enhancing lesions on MRI brain were modeled with midpoint survival analyses, adjusted for PS-quintile.

Results: 741 children (66% female, 15% CIS) began therapy before 18 years, 197 with newer and 544 with injectable DMTs. Those started on newer DMTs were older (15.2 vs. injectable 14.4 years, p=0.001) and less likely to have a monofocal presentation (37% vs. injectable 55%, p<0.001). In PS-quintile adjusted analysis, those started on newer DMTs had lower relapse rate than those on injectables (rate ratio 0.45, 95% CI 0.29–0.70, p<0.001; rate difference 0.27, 95% CI 0.14–0.40, p=0.004). One would need to treat with newer over injectable DMTs for 3.7 person-years to prevent one relapse. Those started on newer DMTs also had lower rate of new/enlarging T2 (HR 0.51, 95% CI 0.36–0.72, p<0.001) and gadolinium-enhancing lesions (HR 0.38, 95% CI 0.23–0.63, p<0.001) than those on injectables.

Conclusions: Initial treatment of pediatric MS/CIS with newer DMTs led to better disease activity control compared to injectables, supporting greater effectiveness of newer therapies. Long-term safety data for newer DMTs is required.

Disclosure: Dr. Krysko has received research support from MS fellowship grant from NMSS; MS fellowship grant from Biogen.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.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. Speaker’s 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. 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. Rutatangwa has received research support from She is supported by a Biogen MS fellowship grant..Dr. Aaen has received research support from Biogen.Dr. Belman has nothing to disclose. Dr. Benson has received research support from She has received funding for research unrelated to this work for a Biogen sponsored clinical trial..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. Gorman has received research support from He has participated in clinical trials funded by Novartis and Biogen, and received research funding from Pfizer..Dr. Goyal holds stock and/or stock options in IBM Stock.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. Moodley has nothing to disclose. Dr. Ness has received research support from Chugai-Roche.. 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. 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. Tillema has received research support from He has received grant support from NIH and the NMSS.. Dr. Waltz has nothing to disclose. Dr. Casper has nothing to disclose. 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.