TY - JOUR
T1 - Real-World Effectiveness of Initial Disease-Modifying Therapies in Pediatric Multiple Sclerosis
AU - Krysko, Kristen M.
AU - Graves, Jennifer S.
AU - Rensel, Mary
AU - Weinstock-Guttman, Bianca
AU - Rutatangwa, Alice
AU - Aaen, Gregory
AU - Belman, Anita
AU - Benson, Leslie
AU - Chitnis, Tanuja
AU - Gorman, Mark
AU - Goyal, Manu S.
AU - Harris, Yolanda
AU - Krupp, Lauren
AU - Lotze, Timothy
AU - Mar, Soe
AU - Moodley, Manikum
AU - Ness, Jayne
AU - Rodriguez, Moses
AU - Rose, John
AU - Schreiner, Teri
AU - Tillema, Jan Mendelt
AU - Waltz, Michael
AU - Casper, T. Charles
AU - Waubant, Emmanuelle
N1 - Funding Information:
Several companies manufacture drugs for MS that are studied in this paper, including Bayer (interferon‐β1b SC), Biogen (interferon‐β1a IM, peginterferon‐β1a, dimethyl fumarate, natalizumab), EMD Serono (interferon‐β1a SC), Genentech/Roche (rituximab, ocrelizumab), Genzyme (alemtuzumab, teriflunomide), Novartis (interferon‐β1b SC, fingolimod), and Teva (glatiramer acetate). K.M.K. and A.R. have received MS fellowship grants from Biogen. J.S.G. has received grants from Biogen, and personal fees from Novartis and Genentech. M.Re. has served on an advisory board or panel for EMD Serono and Biogen, as a consultant for Biogen, Teva, Genzyme, and Novartis, and as a speaker for Genzyme and Biogen, and has received commercial research support from Novartis, Biogen, and Genentech and educational grants from Genzyme. B.W.‐G. has received personal fees from Biogen, Novartis, EMD Serono, and Genentech, and grants from Biogen, Novartis, EMD Serono, and Genentech. L.B. has received funding for a clinical trial from Biogen. T.C. has done consulting for Biogen, Novartis, Genzyme, Bayer, and Genentech, and has received grants from Novartis and EMD Serono. M.Gor. has participated in clinical trials funded by Novartis and Biogen. L.K. has received consulting fees from Biogen, EMD Serono, Genzyme, and Novartis, and research support from Biogen and Novartis. J.N. has participated in clinical trials funded by Novartis and Roche. J.R. has research support from Teva and Biogen, and unrestricted educational grants from Teva, Biogen, Novartis, and Genentech. T.S. has research support from Biogen. The remaining authors have nothing to report.
Funding Information:
This study was funded by the National Multiple Sclerosis Society (HC‐1509‐06233, T.C.C.). K.M.K. is funded by a Sylvia Lawry Physician Fellowship from the National Multiple Sclerosis Society (FP‐1605‐08753).
Publisher Copyright:
© 2020 American Neurological Association
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Objective: To assess real-world effectiveness of initial treatment with newer compared to injectable disease-modifying therapies (DMTs) on disease activity in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS). 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-β, glatiramer acetate) DMTs. Propensity scores (PSs) were computed, 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 brain magnetic resonance imaging were modeled with midpoint survival analyses, adjusted for PS-quintile. Results: A total of 741 children 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. In PS-quintile–adjusted analysis, those on newer DMTs had a lower relapse rate than those on injectables (rate ratio = 0.45, 95% confidence interval (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 rather than injectable DMTs for 3.7 person-years to prevent 1 relapse. Those started on newer DMTs had a lower rate of new/enlarging T2 (hazard ratio [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. Interpretation: 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 are required. ANN NEUROL 2020 ANN NEUROL 2020;88:42–55.
AB - Objective: To assess real-world effectiveness of initial treatment with newer compared to injectable disease-modifying therapies (DMTs) on disease activity in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS). 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-β, glatiramer acetate) DMTs. Propensity scores (PSs) were computed, 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 brain magnetic resonance imaging were modeled with midpoint survival analyses, adjusted for PS-quintile. Results: A total of 741 children 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. In PS-quintile–adjusted analysis, those on newer DMTs had a lower relapse rate than those on injectables (rate ratio = 0.45, 95% confidence interval (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 rather than injectable DMTs for 3.7 person-years to prevent 1 relapse. Those started on newer DMTs had a lower rate of new/enlarging T2 (hazard ratio [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. Interpretation: 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 are required. ANN NEUROL 2020 ANN NEUROL 2020;88:42–55.
UR - http://www.scopus.com/inward/record.url?scp=85084581510&partnerID=8YFLogxK
U2 - 10.1002/ana.25737
DO - 10.1002/ana.25737
M3 - Article
C2 - 32267005
AN - SCOPUS:85084581510
VL - 88
SP - 42
EP - 55
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 1
ER -