TY - JOUR
T1 - Therapeutic Response in Pediatric Neuromyelitis Optica Spectrum Disorder
AU - the US Network of Pediatric MS Centers
AU - Pizzolato Umeton, Raffaella
AU - Waltz, Michael
AU - Aaen, Gregory S.
AU - Benson, Leslie
AU - Gorman, Mark
AU - Goyal, Manu
AU - Graves, Jennifer S.
AU - Harris, Yolanda
AU - Krupp, Lauren
AU - Lotze, Timothy E.
AU - Shukla, Nikita M.
AU - Mar, Soe
AU - Ness, Jayne
AU - Rensel, Mary
AU - Schreiner, Teri
AU - Tillema, Jan Mendelt
AU - Roalstad, Shelly
AU - Rodriguez, Moses
AU - Rose, John
AU - Waubant, Emmanuelle
AU - Weinstock-Guttman, Bianca
AU - Casper, Charles
AU - Chitnis, Tanuja
N1 - Funding Information:
Sumaira Foundation Unicorn Grant (TSF.NMO19-02) to T.C. The US NPMSC is sponsored by the National MS Society (SI-1808-32326).
Publisher Copyright:
© 2022 American Academy of Neurology.
PY - 2023/2/28
Y1 - 2023/2/28
N2 - Background and ObjectiveNeuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition, which can lead to significant disability, and up to 3%-5% of the cases have a pediatric onset. There are limited studies to guide physicians in disease-modifying treatment (DMT) choices for children with NMOSD. Methods: This retrospective cohort study evaluated children with NMOSD cases followed at 12 clinics in the US Network of Pediatric MS Centers. Cases were classified as aquaporin-4 antibody positive (AQP4+) and double seronegative (DS) when negative for AQP4+ and for myelin oligodendrocyte glycoprotein (MOG) antibody. The effect of initial DMTs including rituximab, mycophenolate, azathioprine, and IV immunoglobulin (IVIg) on the annualized relapse rate (ARR) was assessed by negative binomial regression. Time to disability progression (EDSS score increase ≥1.0 point) was modeled with a Cox proportional-hazards model. Results: A total of 91 children with NMOSD were identified: 77 AQP4+ and 14 DS (85.7% females; 43.2% White and 46.6% African American). Eighty-one patients were started on a DMT, and 10 were treatment naive at the time of the analysis. The ARR calculated in all serogroups was 0.25 (95% CI 0.13-0.49) for rituximab, 0.33 (95% CI 0.19-0.58) for mycophenolate, 0.40 (95% CI 0.13-1.24) for azathioprine, and 0.54 (95% CI 0.28-1.04) for IVIg. The ARR in the AQP4+ subgroup was 0.28 (95% CI 0.14-0.55) for rituximab, 0.39 (95% CI 0.21-0.70) for mycophenolate, 0.41 (95% CI 0.13-1.29) for azathioprine, and 0.54 (95% CI 0.23-1.26) for IVIg. The ARR in the treatment-naive group was 0.97 (95% CI 0.58-1.60) in all serogroups and 0.91 (95% CI 0.53-1.56) in the AQP4+ subgroup. None of the initial DMT had a statistically significant effect on EDSS progression. Discussion: The use of DMTs, particularly rituximab, is associated with a lowered annualized relapse rate in children with NMOSD AQP4+.Classification of EvidenceThis study provides Class IV evidence that use of disease-modifying treatments is associated with a lowered annualized relapse rate in children with NMOSD AQP4+.
AB - Background and ObjectiveNeuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition, which can lead to significant disability, and up to 3%-5% of the cases have a pediatric onset. There are limited studies to guide physicians in disease-modifying treatment (DMT) choices for children with NMOSD. Methods: This retrospective cohort study evaluated children with NMOSD cases followed at 12 clinics in the US Network of Pediatric MS Centers. Cases were classified as aquaporin-4 antibody positive (AQP4+) and double seronegative (DS) when negative for AQP4+ and for myelin oligodendrocyte glycoprotein (MOG) antibody. The effect of initial DMTs including rituximab, mycophenolate, azathioprine, and IV immunoglobulin (IVIg) on the annualized relapse rate (ARR) was assessed by negative binomial regression. Time to disability progression (EDSS score increase ≥1.0 point) was modeled with a Cox proportional-hazards model. Results: A total of 91 children with NMOSD were identified: 77 AQP4+ and 14 DS (85.7% females; 43.2% White and 46.6% African American). Eighty-one patients were started on a DMT, and 10 were treatment naive at the time of the analysis. The ARR calculated in all serogroups was 0.25 (95% CI 0.13-0.49) for rituximab, 0.33 (95% CI 0.19-0.58) for mycophenolate, 0.40 (95% CI 0.13-1.24) for azathioprine, and 0.54 (95% CI 0.28-1.04) for IVIg. The ARR in the AQP4+ subgroup was 0.28 (95% CI 0.14-0.55) for rituximab, 0.39 (95% CI 0.21-0.70) for mycophenolate, 0.41 (95% CI 0.13-1.29) for azathioprine, and 0.54 (95% CI 0.23-1.26) for IVIg. The ARR in the treatment-naive group was 0.97 (95% CI 0.58-1.60) in all serogroups and 0.91 (95% CI 0.53-1.56) in the AQP4+ subgroup. None of the initial DMT had a statistically significant effect on EDSS progression. Discussion: The use of DMTs, particularly rituximab, is associated with a lowered annualized relapse rate in children with NMOSD AQP4+.Classification of EvidenceThis study provides Class IV evidence that use of disease-modifying treatments is associated with a lowered annualized relapse rate in children with NMOSD AQP4+.
UR - http://www.scopus.com/inward/record.url?scp=85149053583&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000201625
DO - 10.1212/WNL.0000000000201625
M3 - Article
C2 - 36460473
AN - SCOPUS:85149053583
SN - 0028-3878
VL - 100
SP - E985-E994
JO - Neurology
JF - Neurology
IS - 9
ER -