New progress in the treatment of neuromyelitis optica spectrum disorder with monoclonal antibodies (Review)

Xie, Qin; Sun, Mengjiao; Sun, Jing; Zheng, Ting; Wang, Manxia

doi:10.3892/etm.2020.9579

Cited by 6 publications

(6 citation statements)

References 55 publications

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“…Before eculizumab initiation, the patient's EDSS score was 4–5, but it reduced to 3 during eculizumab therapy, at which point the patient was also relapse-free ( Figure 1 ). There is a common misconception that damage caused during NMOSD relapse is irreversible; however, the improvements in EDSS score seen in our patient are corroborated by the findings of several studies reporting reductions in EDSS scores in response to targeted treatment ( 23 , 24 ). Our patient remained relapse-free during the 12 months after stopping eculizumab therapy, even though she received no other therapy.…”

Section: Discussionsupporting

confidence: 84%

Eculizumab in the Treatment of Aquaporin-4 Seronegative Neuromyelitis Optica Spectrum Disorder: A Case Report

et al. 2021

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Objective: To report the case of a 35-year-old woman with treatment-resistant aquaporin-4 (AQP-4) immunoglobulin G (IgG) seronegative neuromyelitis optica spectrum disorder (NMOSD) successfully treated with eculizumab (a terminal complement inhibitor).Methods: The investigational procedures and treatment regimens the patient received were documented over 8 years [2012 (first presentation) to 2020].Results: The patient presented with subacute onset of lower-limb weakness and numbness, gait imbalance, and urinary incontinence. Magnetic resonance imaging (MRI) showed abnormalities in the thoracic spine from T7 to T10, but brain and cervical spine scans, visual evoked potential latencies, and IgG index were normal; cerebrospinal fluid pleocytosis and oligoclonal bands were both present. After treatment with intravenous methylprednisolone 1 g/day for 5 days, the patient was discharged without medication to acute rehabilitation but experienced relapses from 2012 to 2014. She was treated with oral prednisone (initiated at 40 mg/day in 2014; the dose was halved in 2015 due to weight gain) and mycophenolate mofetil (MMF) 1 g twice daily (from June 2015), but between 2014 and 2019 experienced 4–5 relapses/year, requiring treatment with intravenous methylprednisolone, with added maintenance plasma exchange from 2018 onwards. Although the patient tested negative for antibodies to AQP-4 and myelin oligodendrocyte glycoprotein, she was diagnosed with NMOSD in February 2017, based on recurrent episodes of longitudinal extensive transverse myelitis, MRI changes, and area postrema syndrome. By 2018 the patient needed a cane to walk. Prednisone and MMF were discontinued mid-2018, and rituximab was prescribed from July 2018 (maintenance regimen two 1 g doses 2 weeks apart every 6 months) but discontinued in July 2019 owing to lack of significant improvement. From July 2019 eculizumab was prescribed for 6 months (900 mg weekly for the first four doses, then 1200 mg every 2 weeks). The patient had no relapses or adverse events during and after eculizumab treatment (as of August 2020) and was able to walk unaided; her Expanded Disability Status Scale score improved from 4–5 during 2015–2018 to 2 in 2020 following eculizumab treatment.Conclusion: Eculizumab shows promise as a treatment for AQP-4 IgG-seronegative NMOSD and further studies are warranted.

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Section: Discussionsupporting

confidence: 84%

Eculizumab in the Treatment of Aquaporin-4 Seronegative Neuromyelitis Optica Spectrum Disorder: A Case Report

et al. 2021

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“…Plasmapheresis is the preferred immunomodulatory treatment for patients refractory to steroid treatment [ 2 ]. There have been recent advancements in the long-term management of NMOSD, with the approval of 3 immunomodulatory agents, including eculizumab (complement factor C5 inhibitor), inebilizumab (CD-19 inhibitor), and satralizumab (IL-6 receptor inhibitor) [ 15 , 16 ]. Rituximab has also shown a beneficial effect, with a relapse prevention rate of up to 67% [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…Rituximab has also shown a beneficial effect, with a relapse prevention rate of up to 67% [ 16 ]. Other commonly used immunosuppressants include azathioprine, mycophenolate mofetil, and tocilizumab [ 15 ]. Specific monoclonal antibodies, including ublituximab, which targets CD-20, and aquaporumab, which binds to AQP-4 directly, are in the early stages of development and require large-scale clinical trials before use in clinical practice [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Other commonly used immunosuppressants include azathioprine, mycophenolate mofetil, and tocilizumab [ 15 ]. Specific monoclonal antibodies, including ublituximab, which targets CD-20, and aquaporumab, which binds to AQP-4 directly, are in the early stages of development and require large-scale clinical trials before use in clinical practice [ 15 ]. In our patient, rituximab was the drug of choice, resulting in no clinical or radiological relapse for 4 months.…”

Section: Discussionmentioning

confidence: 99%

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A Missed Case of Area Postrema Syndrome Presenting with Neuromyelitis Optica Spectrum Disorder

et al. 2021

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Patient: Female, 33-year-old Final Diagnosis: Neuromyelitis optica Symptoms: Altered mental status • ataxia • fever • hiccups • hypersomnolence • nausea • vomiting Medication: — Clinical Procedure: Aquaporin-4 antibody serological testing • cerebrospinal fluid analysis • electroencephalogram Specialty: Gastroenterology and Hepatology • Neurology • Radiology Objective: Rare disease Background: Neuromyelitis optica spectrum disorder (NMOSD), which is also known as Devic disease, is a chronic disorder of the brain and spinal cord that includes inflammation of the optic nerve and spinal cord. Area postrema syndrome (APS) is due to involvement of the bulbar emetic reflex center, and has previously been described in NMOSD. Patients with APS may present with nausea, vomiting, or hiccups. This report is of a 33-year-old Asian American woman with history of APS who presented with NMOSD. Case Report: A 33-year-old Southeast Asian woman, 2 months postpartum, presented with fever, hypersomnolence, altered mental status, and difficulty ambulating. Neurological examination revealed a lethargic woman with poor attention span, broad-based gait ataxia, and positive Romberg’s sign. Laboratory work-up showed sodium 123 milliequivalent/L (mEq/L). Brain magnetic resonance imaging (MRI) with contrast revealed bilateral, non-enhancing, patchy fluid-attenuated inversion recovery (FLAIR) hyperintensities in the anteroinferomedial thalamus extending to the mammillary bodies. Additional history revealed hospitalization for intractable nausea, vomiting, and hiccups 2 years ago. NMOSD was confirmed with positive AQP-4 antibody, prompting treatment with intravenous (i.v.) methylprednisolone, followed by plasmapheresis. Repeat brain MRI showed mild improvement of bilateral thalamic FLAIR hyperintensities and no clinical recurrence was reported with Rituximab treatment. Conclusions: This case highlights the importance of the diagnostic diligence required for NMOSD diagnosis. Multiple etiologies can mimic the clinical presentation of acute diencephalic syndrome; thus, a broad differential needs to be considered. This report presents the diagnostic work-up and management of a patient with a complex neurological condition that was diagnosed as NMOSD.

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“…For instance, because the repopulation of B cells is relevant to the relapse rate of NMOSD, immunotherapies targeting B cells and related proteins were demonstrated to be effective in treating NMOSD 13 , 14 , and several drugs have been licenced and applied as clinical therapies 15 , 16 . In addition to B cell depletion therapy, numerous kinds of treatments have been demonstrated to be effective in treating NMOSD, such as interleukin (IL)-6 receptor antagonists, complement blockers and other monoclonal antibodies (such as aquaporumab, bevacizumab and ublituximab) 17 . The efficacy of novel therapies (including eculizumab to target the complement system, satralizumab to target the IL-6 receptor, and inebilizumab to target B cells) has been assessed by randomized controlled trials of patients with NMOSD, and the results show that these therapies were beneficial in preventing autoimmune attacks, but the studies also show various efficacy, safety, tolerability, and practical considerations associated with these drugs 18 .…”

Section: Introductionmentioning

confidence: 99%

The role and mechanisms of Microglia in Neuromyelitis Optica Spectrum Disorders

Li¹,

Liu²,

Tan³

et al. 2021

Int. J. Med. Sci.

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Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune neurological disease that can cause blindness and disability. As the major mediators in the central nervous system, microglia plays key roles in immunological regulation in neuroinflammatory diseases, including NMOSD. Microglia can be activated by interleukin (IL)-6 and type I interferons (IFN-Is) during NMOSD, leading to signal transducer and activator of transcription (STAT) activation. Moreover, complement C3a secreted from activated astrocytes may induce the secretion of complement C1q, inflammatory cytokines and progranulin (PGRN) by microglia, facilitating injury to microglia, neurons, astrocytes and oligodendrocytes in an autocrine or paracrine manner. These processes involving activated microglia ultimately promote the pathological course of NMOSD. In this review, recent research progress on the roles of microglia in NMOSD pathogenesis is summarized, and the mechanisms of microglial activation and microglialmediated inflammation, and the potential research prospects associated with microglial activation are also discussed.

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New progress in the treatment of neuromyelitis optica spectrum disorder with monoclonal antibodies (Review)

Cited by 6 publications

References 55 publications

Eculizumab in the Treatment of Aquaporin-4 Seronegative Neuromyelitis Optica Spectrum Disorder: A Case Report

Eculizumab in the Treatment of Aquaporin-4 Seronegative Neuromyelitis Optica Spectrum Disorder: A Case Report

A Missed Case of Area Postrema Syndrome Presenting with Neuromyelitis Optica Spectrum Disorder

The role and mechanisms of Microglia in Neuromyelitis Optica Spectrum Disorders

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