Anti-CD20 therapies have established efficacy in the treatment of immune-mediated neurological and non-neurological diseases. Rituximab, one of the first B-cell-directed therapies, is relatively inexpensive compared to newer anti-CD20 molecules, is available in many countries, and has been used off-label in pediatric patients with neuroimmune conditions. The objective of this paper is to describe the experience with rituximab in pediatric multiple sclerosis and other inflammatory immune-mediated disorders of the central nervous system (CNS), and to define a protocol for its use in clinical practice, in particular addressing doses, interval of administration, duration of treatment, and tests to perform at baseline and during follow-up.
HofmannKClauderAKManzRA.Targeting B cells and plasma cells in autoimmune diseases. Front Immunol2018; 9: 835.
2.
SmulskiCREibelH.BAFF and BAFF-receptor in B cell selection and survival. Front Immunol2018; 9: 2285.
3.
CohenSBEmeryPGreenwaldMW, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum2006; 54(9): 2793–2806.
4.
StoneJHMerkelPASpieraR, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med2010; 363: 221–232.
5.
KaegiCWuestBSchreinerJ, et al. Systematic review of safety and efficacy of rituximab in treating immune-mediated disorders. Front Immunol2019; 10: 1990.
6.
HauserSLBar-OrAComiG, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med2017; 376(3): 221–234.
7.
MontalbanXHauserSLKapposL, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med2017; 376(3): 209–220.
IneichenBVMoridiTGranbergT, et al. Rituximab treatment for multiple sclerosis. Mult Scler2020; 26(2): 137–152.
10.
HauserSLWaubantEArnoldDL, et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med2008; 358(7): 676–688.
11.
HawkerKO’ConnorPFreedmanMS, et al. Rituximab in patients with primary progressive multiple sclerosis: Results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol2009; 66(4): 460–471.
12.
HuYNieHYuHH, et al. Efficacy and safety of rituximab for relapsing-remitting multiple sclerosis: A systematic review and meta-analysis. Autoimmun Rev2019; 18(5): 542–548.
13.
GranqvistMBoremalmMPoorghobadA, et al. Comparative effectiveness of rituximab and other initial treatment choices for multiple sclerosis. JAMA Neurol2018; 75(3): 320–327.
14.
AlpingPFrisellTNovakovaL, et al. Rituximab versus fingolimod after natalizumab in multiple sclerosis patients. Ann Neurol2016; 79(6): 950–958.
15.
BoremalmMJutoAAxelssonM, et al. Natalizumab, rituximab and fingolimod as escalation therapy in multiple sclerosis. Eur J Neurol2019; 26(8): 1060–1067.
16.
LunaGAlpingPBurmanJ, et al. Infection risks among patients with multiple sclerosis treated with fingolimod, natalizumab, rituximab, and injectable therapies. JAMA Neurol2019; 77: e193365.
17.
ZoehnerGMicleaASalmenA, et al. Reduced serum immunoglobulin G concentrations in multiple sclerosis: Prevalence and association with disease-modifying therapy and disease course. Ther Adv Neurol Disord2019; 12: 1756286419878340.
18.
OshimaYTanimotoTYujiK, et al. Drug-associated progressive multifocal leukoencephalopathy in multiple sclerosis patients. Mult Scler2019; 25(8): 1141–1149.
19.
AlpingPAsklingJJoachim BurmanJ, et al. Cancer risk for fingolimod, natalizumab, and rituximab in multiple sclerosis patients. Ann Neurol2020; 87: 688–699.
20.
DamatoVEvoliAIorioR.Efficacy and safety of rituximab therapy in neuromyelitis optica spectrum disorders: A systematic review and meta-analysis. JAMA Neurol2016; 73(11): 1342–1348.
21.
HuangWWangLZhangB, et al. Effectiveness and tolerability of immunosuppressants and monoclonal antibodies in preventive treatment of neuromyelitis optica spectrum disorders: A systematic review and network meta-analysis. Mult Scler Relat Disord2019; 35: 246–252.
22.
JariusSRuprechtKKleiterI, et al. MOG-IgG in NMO and related disorders: A multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflammation2016; 2713(1): 280.
23.
RamanathanSMohammadSTantsisE, et al. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J Neurol Neurosurg Psychiatry2018; 89(2): 127–137.
24.
DurozardPRicoABoutiereC.Comparison of the response to rituximab between myelin oligodendrocyte glycoprotein and aquaporin-4 antibody diseases. Ann Neurol2020; 87(2): 256–266.
25.
DaleRCBrilotFDuffyLV, et al. Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology2014; 83(2): 142–150.
26.
LotzeTENorthropJLHuttonGJ, et al. Spectrum of pediatric neuromyelitis optica. Pediatrics2008; 122(5): e1039–e1047.
27.
McKeonALennonVALotzeT, et al. CNS aquaporin-4 autoimmunity in children. Neurology2008; 71(2): 93–100.
28.
BeresSJGravesJWaubantE.Rituximab use in pediatric central demyelinating disease. Pediatr Neurol2014; 51(1): 114–118.
29.
NosadiniMAlperGRineyCJ, et al. Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm2016; 3(1): e188.
30.
HacohenYWongYYLechnerC, et al. Disease course and treatment responses in children with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease. JAMA Neurol2018; 75(4): 478–487.
31.
MaoLYangLKessiM, et al. Myelin oligodendrocyte glycoprotein (MOG) antibody diseases in children in Central South China: Clinical features, treatments, influencing factors, and outcomes. Front Neurol2019; 10: 868.
32.
AlbassamFLongoniGYeaC, et al. Rituximab in children with myelin oligodendrocyte glycoprotein antibody and relapsing neuroinflammatory disease. Dev Med Child Neurol2020; 62: 390–395.
33.
VartzelisGMaritsiDNikolaidouM, et al. Rituximab in paediatric onset multiple sclerosis: A case series. Case Rep Pediatr2019; 2019: 8731613.
34.
SalzerJLyckeJWickströmR, et al. Rituximab in paediatric onset multiple sclerosis: A case series. J Neurol2016; 263(2): 322–326.
35.
KornekBBreuMSeidlR, et al. Rituximab use in pediatric multiple sclerosis (in preparation).
36.
KryskoKMGravesJRenselM, et al. Real-world effectiveness of initial disease-modifying therapies in pediatric multiple sclerosis. Ann Neurol. Epub ahead of print 8 April 2020. DOI: 10.1002/ana.25737.
37.
KryskoKMGravesJRenselM, et al. Use of newer disease-modifying therapies in pediatric multiple sclerosis in the US. Neurology2018; 91(19): e1778–e1787.
38.
ChitnisTTenembaumSBanwellB, et al. Consensus statement: Evaluation of new and existing therapeutics for pediatric multiple sclerosis. Mult Scler2012; 18(1): 116–127.
39.
FarezMFCorrealeJArmstrongMJ, et al. Practice guideline update summary: Vaccine-preventable infections and immunization in multiple sclerosis: Report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology. Neurology2019; 93(13): 584–594.
40.
ChitnisTWaubantE.B-cell depletion in children with neuroimmunologic conditions-the learning curve. Neurology2014; 83: 111–112.
41.
AnnovazziPCapobiancoMMoiolaL, et al. Rituximab in the treatment of neuromyelitis optica: A multicentre Italian observational study. J Neurol2016; 263(9): 1727–1735.
42.
NoviGBovisFCapobiancoM, et al. Efficacy of different rituximab therapeutic strategies in patients with neuromyelitis optica spectrum disorders. Mult Scler Relat Disord2019; 36: 101430.
43.
KhojahAMMillerMLKlein-GitelmanMS, et al. Rituximab-associated hypogammaglobulinemia in pediatric patients with autoimmune diseases. Pediatr Rheumatol Online J2019; 17(1): 61.
44.
GreenbergBMGravesDRemingtonG, et al. Rituximab dosing and monitoring strategies in neuromyelitis optica patients: Creating strategies for therapeutic success. Mult Scler2012; 18(7): 1022–1026.
45.
EllrichmannGBolzJPeschkeM, et al. Peripheral CD19+ B-cell counts and infusion intervals as a surrogate for long-term B-cell depleting therapy in multiple sclerosis and neuromyelitis optica/neuromyelitis optica spectrum disorders. J Neurol2019; 266(1): 57–67.
46.
KimS-HKimYKimG, et al. Less frequent rituximab retreatment maintains remission of neuromyelitis optica spectrum disorder, following long-term rituximab treatment. J Neurol Neurosurg Psychiatry2019; 90(4): 486–487.
47.
YangCSYangLLiT, et al. Responsiveness to reduced dosage of rituximab in Chinese patients with neuromyelitis optica. Neurology2013; 81(8): 710–713.
48.
PanSYuHSurtiA, et al. Pharmacodynamics of rituximab on B lymphocytes in paediatric patients with autoimmune diseases. Br J Clin Pharmacol2019; 85(8): 1790–1797.
