Early Initiation of Tocilizumab Treatment Against Moderate-to-Severe Myelitis in Neuromyelitis Optica Spectrum Disorder

Du, Chen; Zeng, Pei; Han, Jinrui; Zhang, Tianxiang; Jia, Dongmei; Shi, Fu‐Dong; Zhang, Chao

doi:10.3389/fimmu.2021.660230

Cited by 12 publications

(6 citation statements)

References 31 publications

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“…Our findings agree with other retrospective studies that found an increased concentration of CSF IL-6 in NMOSD (17,28,29) and MOGAD (17,30) compared to MS. Added to our results, these findings suggest that CSF IL-6 measurement may impact early diagnosis, while cytokine measurement is easy and fast to perform as compared to aquaporin-4 or MOG antibody, and may guide early therapeutic action, in suspected NMOSD/ MOGAD patients. Moreover, tocilizumab, an IL-6 receptor blockade therapy, has shown promising efficacy in NMOSD (31)(32)(33) and has been reported to be effective in relapsing steroid-dependent MOGAD (31,34), reinforcing the impact of the IL-6 pathway in these diseases. In contrast, CSF CD25 could not separate MSARD from NMOSD and MOGAD, as it has already been suggested in two previously published retrospective studies (17,35).…”

Section: Discussionmentioning

confidence: 99%

Kappa Free Light Chains, Soluble Interleukin-2 Receptor, and Interleukin-6 Help Explore Patients Presenting With Brain White Matter Hyperintensities

Levraut¹,

Landes²,

Mondot³

et al. 2022

Front. Immunol.

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IntroductionMany patients are referred to multiple sclerosis (MS) tertiary centers to manage brain white matter hyperintensities (WMH). Multiple diagnoses can match in such situations, and we lack proper tools to diagnose complex cases.ObjectiveThis study aimed to prospectively analyze and correlate with the final diagnosis, cerebrospinal fluid (CSF) interleukin (IL)-1β, soluble IL-2 receptor (CD25), IL-6, IL-10, and kappa free light chains (KFLC) concentrations in patients presenting with brain WMH.MethodsAll patients over 18 years addressed to our MS tertiary center for the diagnostic workup of brain WMH were included from June 1, 2020, to June 1, 2021. Patients were separated into three groups—MS and related disorder (MSARD), other inflammatory neurological disorder (OIND), and non-inflammatory neurological disorder (NIND) groups—according to clinical presentation, MRI characteristics, and biological workup.ResultsA total of 176 patients (129 women, mean age 45.8 ± 14.7 years) were included. The diagnosis was MSARD (n = 88), OIND (n = 35), and NIND (n = 53). Median CSF KFLC index and KFLC intrathecal fraction (IF) were higher in MSARD than in the OIND and NIND groups; p < 0.001 for all comparisons. CSF CD25 and IL-6 concentrations were higher in the OIND group than in both the MSARD and NIND groups; p < 0.001 for all comparisons. KFLC index could rule in MSARD when compared to NIND (sensitivity, 0.76; specificity, 0.91) or OIND (sensitivity, 0.73; specificity, 0.76). These results were similar to those with oligoclonal bands (sensitivity, 0.59; specificity, 0.98 compared to NIND; sensitivity, 0.59; specificity, 0.88 compared to OIND). In contrast, elevated CSF CD25 and IL-6 could rule out MSARD when compared to OIND (sensitivity, 0.58 and 0.88; specificity, 0.95 and 0.74, respectively).DiscussionOur results show that, as OCBs, KFLC biomarkers are helpful tools to rule in MSARD, whereas elevated CSF CD25 and IL-6 rule out MSARD. Interestingly, CSF IL-6 concentration could help identify neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, and central nervous system (CNS) vasculitis. These results need to be confirmed within more extensive and multicentric studies. Still, they sustain that KFLC, CSF CD25, and CSF IL-6 could be reliable biomarkers in brain WMH diagnostic workup for differentiating MSARD from other brain inflammatory MS mimickers.

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Section: Discussionmentioning

confidence: 99%

Kappa Free Light Chains, Soluble Interleukin-2 Receptor, and Interleukin-6 Help Explore Patients Presenting With Brain White Matter Hyperintensities

Levraut¹,

Landes²,

Mondot³

et al. 2022

Front. Immunol.

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“…The onset of action can be expected after a few weeks. One study investigating tocilizumab treatment within 2 weeks after an NMOSD attack showed favorable effects on the disease course [ 63 ]. Nevertheless, data on the long-term use of tocilizumab in NMOSD remain scarce and mainly arise from other indications.…”

Section: Treatment Of Nmosd: General Aspects and Outcome Measuresmentioning

confidence: 99%

Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management

Kuempfel¹,

Giglhuber²,

Aktaş³

et al. 2023

J Neurol

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This manuscript presents practical recommendations for managing acute attacks and implementing preventive immunotherapies for neuromyelitis optica spectrum disorders (NMOSD), a rare autoimmune disease that causes severe inflammation in the central nervous system (CNS), primarily affecting the optic nerves, spinal cord, and brainstem. The pillars of NMOSD therapy are attack treatment and attack prevention to minimize the accrual of neurological disability. Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) are a diagnostic marker of the disease and play a significant role in its pathogenicity. Recent advances in understanding NMOSD have led to the development of new therapies and the completion of randomized controlled trials. Four preventive immunotherapies have now been approved for AQP4-IgG-positive NMOSD in many regions of the world: eculizumab, ravulizumab - most recently-, inebilizumab, and satralizumab. These new drugs may potentially substitute rituximab and classical immunosuppressive therapies, which were as yet the mainstay of treatment for both, AQP4-IgG-positive and -negative NMOSD. Here, the Neuromyelitis Optica Study Group (NEMOS) provides an overview of the current state of knowledge on NMOSD treatments and offers statements and practical recommendations on the therapy management and use of all available immunotherapies for this disease. Unmet needs and AQP4-IgG-negative NMOSD are also discussed. The recommendations were developed using a Delphi-based consensus method among the core author group and at expert discussions at NEMOS meetings.

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“…Treatment for acute attacks consists of high-dose glucocorticosteroid (GC)-and apheresis therapy. The early initiation of B-cell and interleukin-(IL-6) directed therapies as add-on treatment to highdose steroid therapy during acute attacks improved outcomes in single case series but need to be evaluated in bigger studies [28,29]. The improved knowledge of the pathophysiology in NMOSD has led to the initiation of randomized and controlled trials with B-cell directed therapies, IL-6 directed therapy and anti-complement therapy.…”

Section: Therapeutic Approaches In Neuromyelitis Optica Spectrum Diso...mentioning

confidence: 99%

Pathomechanisms in demyelination and astrocytopathy: autoantibodies to AQP4, MOG, GFAP, GRP78 and beyond

Mader

Kümpfel

Meinl

2022

Current Opinion in Neurology

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Purpose of reviewThe purpose of this review is to highlight the recently emerging pathomechanisms of diseases associated with autoantibodies to AQP4, MOG, GFAP, GRP78 and further novel targets. We discuss novel biomarkers and therapeutic approaches.Recent findingsAlthough complement-mediated cytotoxicity (CDC) is regarded as the major effector mechanism for AQP4-IgG in neuromyelitis optica spectrum disorders (NMOSD), recent studies helped to understand the relevance of complement-independent effector mechanisms. For MOG-IgG mediated diseases the role of CDC is less clear. MOG-IgG may trigger a tightly controlled FcR and BTK-driven microglia proliferative response in MOG-antibody-associated diseases. Differences of antibody-mediated tissue damage may reflect differential response to therapy. In addition, antibodies to GFAP, GRP78 and further novel targets have been implicated in demyelination and astrocytopathy.SummaryElucidating the whole spectrum of effector functions in diseases mediated by AQP4-IgG and MOG-IgG and understanding the role of additional novel autoantibodies involved in demyelination and astrocytopathy may guide further novel treatment decisions.

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Early Initiation of Tocilizumab Treatment Against Moderate-to-Severe Myelitis in Neuromyelitis Optica Spectrum Disorder

Cited by 12 publications

References 31 publications

Kappa Free Light Chains, Soluble Interleukin-2 Receptor, and Interleukin-6 Help Explore Patients Presenting With Brain White Matter Hyperintensities

Kappa Free Light Chains, Soluble Interleukin-2 Receptor, and Interleukin-6 Help Explore Patients Presenting With Brain White Matter Hyperintensities

Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management

Pathomechanisms in demyelination and astrocytopathy: autoantibodies to AQP4, MOG, GFAP, GRP78 and beyond

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