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November 06, 2018; 91 (19) Article

Use of newer disease-modifying therapies in pediatric multiple sclerosis in the US

Kristen M. Krysko, Jennifer Graves, Mary Rensel, Bianca Weinstock-Guttman, Gregory Aaen, Leslie Benson, Tanuja Chitnis, Mark Gorman, Manu Goyal, Lauren Krupp, Timothy Lotze, Soe Mar, Moses Rodriguez, John Rose, Michael Waltz, T. Charles Casper, Emmanuelle Waubant
First published October 17, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006471
Kristen M. Krysko
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Jennifer Graves
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Mary Rensel
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Bianca Weinstock-Guttman
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Gregory Aaen
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Leslie Benson
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Tanuja Chitnis
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Mark Gorman
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Manu Goyal
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Lauren Krupp
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Timothy Lotze
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Soe Mar
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Moses Rodriguez
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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John Rose
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Michael Waltz
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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T. Charles Casper
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Emmanuelle Waubant
From the Department of Neurology (K.M.K., J.G., E.W.), University of California San Francisco; Department of Neurology (M. Rensel), Cleveland Clinic, OH; Department of Neurology (B.W.-G.), State University of New York at Buffalo; Department of Pediatrics (G.A.), Loma Linda University, CA; Department of Neurology (L.B., M. Gorman), Boston Children's Hospital, MA; Department of Neurology (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (M. Goyal, S.M.), Washington University in Saint Louis, MO; Department of Neurology (L.K.), New York University Langone Medical Center, NY; Department of Neurology (T.L.), Texas Children's Hospital, Houston; Department of Neurology (M. Rodriguez), Mayo Clinic, Rochester, MN; and Department of Neurology (J.R.), Biostatistician II (M.W.), and Department of Pediatrics (T.C.C.), University of Utah, Salt Lake City.
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Citation
Use of newer disease-modifying therapies in pediatric multiple sclerosis in the US
Kristen M. Krysko, Jennifer Graves, Mary Rensel, Bianca Weinstock-Guttman, Gregory Aaen, Leslie Benson, Tanuja Chitnis, Mark Gorman, Manu Goyal, Lauren Krupp, Timothy Lotze, Soe Mar, Moses Rodriguez, John Rose, Michael Waltz, T. Charles Casper, Emmanuelle Waubant
Neurology Nov 2018, 91 (19) e1778-e1787; DOI: 10.1212/WNL.0000000000006471

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Abstract

Objective To characterize the use and safety of newer disease-modifying therapies (DMTs) in children with multiple sclerosis (MS) and clinically isolated syndrome (CIS) treated under 18 years of age.

Methods This is a cohort study including children with MS or CIS followed at 12 outpatient practices participating in the US Network of Pediatric MS Centers. DMT use, including duration, dose, and side effects, was analyzed. Newer DMTs were defined as agents receiving Food and Drug Administration approval or with increased use in adult MS after 2005.

Results As of July 2017, 1,019 pediatric patients with MS (n = 748) or CIS (n = 271) were enrolled (65% female, mean onset 13.0 ± 3.9 years, mean follow-up 3.5 ± 3.1 years, median 1.6 visits per year). Of these, 78% (n = 587) with MS and 11% (n = 31) with CIS received DMT before 18 years of age. This consisted of at least one newer DMT in 42%, including dimethyl fumarate (n = 102), natalizumab (n = 101), rituximab (n = 57), fingolimod (n = 37), daclizumab (n = 5), and teriflunomide (n = 3). Among 17%, the initial DMT prescribed was a newer agent (36 dimethyl fumarate, 30 natalizumab, 22 rituximab, 14 fingolimod, 2 teriflunomide). Over the last 10 years, the use of newer agents has increased, particularly in those ≥12 years and to lesser extent in those <12 years. The short-term side effect profiles of newer DMTs did not differ from those reported in adults.

Conclusion Newer DMTs are often used in pediatric MS, and have similar short-term safety, tolerability, and side effect profiles as in adults. These findings may help inform pediatric MS management.

Glossary

CI=
confidence interval;
CIS=
clinically isolated syndrome;
DMT=
disease-modifying therapy;
EDSS=
Expanded Disability Status Scale;
FDA=
Food and Drug Administration;
JCV=
JC virus;
MS=
multiple sclerosis;
OR=
odds ratio

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Coinvestigators are listed at links.lww.com/WNL/A727.

  • Podcast: NPub.org/jpklk4

  • CME Course: NPub.org/cmelist

  • Received March 12, 2018.
  • Accepted in final form July 25, 2018.
  • © 2018 American Academy of Neurology
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