Eculizumab in the treatment of neuromyelitis optica spectrum disorder

Immunotherapy ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 1053-1066
Author(s):  
Katrin Giglhuber ◽  
Achim Berthele
Keyword(s):  
Neuromyelitis Optica ◽  
Controlled Trial ◽  
Water Channel ◽  
Spectrum Disorder ◽  
Phase Iii ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Humanized Monoclonal Antibody ◽  
The Complement System ◽  
Terminal Complement ◽  
Aqp4 Antibody

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the CNS which is distinct from multiple sclerosis and typically presents with a relapsing course of optic neuritis, myelitis and midline brain inflammatory lesions. In at least two-thirds of cases, antibodies against the water channel AQP4 can be found, which lead to an antibody-mediated activation of the complement system with consecutive damage to neuronal structures. Eculizumab, a humanized monoclonal antibody against the terminal complement component 5, was shown to significantly reduce the risk of NMOSD relapse in a Phase III placebo-controlled trial. Based on this, eculizumab (Soliris®) was the first drug to be formally approved for the treatment of anti-AQP4-antibody positive NMOSD in 2019.

Satralizumab in the treatment of neuromyelitis optica spectrum disorder

2021 ◽  
Vol 11 (1) ◽  
pp. 49-59
Author(s):  
Ankelien Duchow ◽  
Judith Bellmann-Strobl
Keyword(s):  
Neuromyelitis Optica ◽  
Subcutaneous Administration ◽  
Spectrum Disorder ◽  
Phase Iii ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Double Blind ◽  
Good Tolerability ◽  
Positive Effects ◽  
Humanized Monoclonal Antibody ◽  
Phase Iii Trials

Neuromyelitis optica spectrum disorder (NMOSD) is a rare and debilitating autoimmune astrocytopathy with a predominantly relapsing disease course. Satralizumab, a humanized monoclonal antibody, was designed to treat NMOSD by targeting the IL-6 receptor. Satralizumab builds on positive experiences of off-label use tocilizumab in recent years. Before 2019, no medications were approved for the treatment of NMOSD. In 2020, satralizumab became the third compound to enter the US market, adding to the complement inhibitor eculizumab and the CD19 inhibitor inebilizumab. Here, we review the two randomized, double-blind, Phase III trials that investigated the subcutaneous administration of satralizumab as add-on treatment and monotherapy. Both studies revealed positive effects concerning the reduction of relapse risk for AQP4 seropositive NMOSD patients and generally good tolerability.

scholarly journals Neuromyelitis optica spectrum disorder in pediatrics. Case report

Case reports ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. 11-18
Author(s):  
Jhon Camacho ◽  
Sebastian Zuleta ◽  
Maria Paula Alba ◽  
Andrea Hernandez ◽  
Carlos Navas
Keyword(s):  
Neuromyelitis Optica ◽  
Interesting Case ◽  
Spectrum Disorder ◽  
Demyelinating Diseases ◽  
Inflammatory Disorder ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
The Central Nervous System ◽  
High Doses ◽  
Aqp4 Antibody ◽  
Timely Treatment

Introduction: Neuromyelitis optica is an inflammatory disorder of the central nervous system that accounts for 5% of demyelinating diseases in pediatrics. Its clinical presentation is variable and associated to the involved area of the central nervous system.Case presentation: This is the case of a 15-year-old patient who consulted several times for nonspecific neurological symptoms. During his last visit to the Clínica Universitaria Colombia in Bogotá, he presented with bilateral optic neuritis, associated with frontal and parietal headache. Immunophenotyping studies were carried out, reporting positive IgG anti-aquaporin 4 antibodies (anti-AQP4 antibody), thus leading to a diagnosis of seropositive neuromyelitis optica spectrum disorder (NMOSD). Management with methylprednisolone pulses was initiated with subsequent outpatient management with rituximab that allowed stabilizing the disease.Discussion: This is an interesting case due to its insidious and uncertain onset in a pediatric patient. It was possible to evaluate clinical and diagnostic differences in relation to its presentation in adults. NMOSD mediated by anti-AQP4 is rare; brain and bone marrow MRI are essential for diagnosis. The treatment of choice for acute conditions consists of high doses of methylprednisolone.Conclusion: This disorder may result in irreversible neurological damage; for this reason, high suspicion is required for early diagnosis and timely treatment.

scholarly journals Neuromyelitis Optica Spectrum Disorder and Anti-MOG Syndromes

Biomedicines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 42 ◽  
Author(s):  
Marco A. Lana-Peixoto ◽  
Natália Talim
Keyword(s):  
Optic Neuritis ◽  
Neuromyelitis Optica ◽  
Area Postrema ◽  
Water Channel ◽  
Clinical Manifestations ◽  
Transverse Myelitis ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Immunosuppressive Drugs ◽  
Spectrum Disorder ◽  
Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein (anti-MOG) syndromes are immune-mediated inflammatory conditions of the central nervous system that frequently involve the optic nerves and the spinal cord. Because of their similar clinical manifestations and habitual relapsing course they are frequently confounded with multiple sclerosis (MS). Early and accurate diagnosis of these distinct conditions is relevant as they have different treatments. Some agents used for MS treatment may be deleterious to NMOSD. NMOSD is frequently associated with antibodies which target aquaporin-4 (AQP4), the most abundant water channel in the CNS, located in the astrocytic processes at the blood-brain barrier (BBB). On the other hand, anti-MOG syndromes result from damage to myelin oligodendrocyte glycoprotein (MOG), expressed on surfaces of oligodendrocytes and myelin sheaths. Acute transverse myelitis with longitudinally extensive lesion on spinal MRI is the most frequent inaugural manifestation of NMOSD, usually followed by optic neuritis. Other core clinical characteristics include area postrema syndrome, brainstem, diencephalic and cerebral symptoms that may be associated with typical MRI abnormalities. Acute disseminated encephalomyelitis and bilateral or recurrent optic neuritis are the most frequent anti-MOG syndromes in children and adults, respectively. Attacks are usually treated with steroids, and relapses prevention with immunosuppressive drugs. Promising emerging therapies for NMOSD include monoclonal antibodies and tolerization.

Inebilizumab for treatment of neuromyelitis optica spectrum disorder

2021 ◽  
Vol 11 (5) ◽  
pp. 341-352
Author(s):  
Mark J Tullman ◽  
Aram Zabeti ◽  
Scott Vuocolo ◽  
Quinn Dinh
Keyword(s):  
Neuromyelitis Optica ◽  
Plasma Cells ◽  
Transverse Myelitis ◽  
Spectrum Disorder ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Neurologic Injury ◽  
Immune Mediated ◽  
The Us ◽  
Us Fda ◽  
Aqp4 Antibody

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease characterized by recurrent optic neuritis and transverse myelitis often resulting in severe disability. Anti-AQP4-immunoglobulin G (IgG) is a pathogenic product of CD19-positive plasma cells found in most, but not all, individuals with NMOSD and is associated with immune-mediated neurologic injury. Inebilizumab, an afucosylated humanized IgG1κ, anti-CD19 monoclonal antibody, may target pathogenic CD19-expressing B cells. In a Phase II/III trial, inebilizumab significantly reduced the proportion of participants experiencing an NMOSD attack and was well tolerated versus placebo. Fewer treated participants had worsening disability than those receiving placebo. Inebilizumab was approved in 2020 by the US FDA for treatment of anti-AQP4 antibody positive NMOSD.

scholarly journals Two Cases of Very-Late-Onset Neuromyelitis Optica Spectrum Disorder (NMOSD) in Patients over the Age of 80

2020 ◽  
Vol 12 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Shunya Fujiwara ◽  
Yasuhiro Manabe ◽  
Ryuta Morihara ◽  
Taijun Yunoki ◽  
Syoichiro Kono ◽  
...  
Keyword(s):  
Neuromyelitis Optica ◽  
Clinical Course ◽  
Late Onset ◽  
Transverse Myelitis ◽  
Spectrum Disorder ◽  
High Dose ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Initial Manifestation ◽  
High Dose Methylprednisolone ◽  
Aqp4 Antibody

We report two cases of very-late-onset neuromyelitis optica spectrum disorder (NMOSD) in patients over the age of 80 with transverse myelopathy as the initial manifestation. In both cases, the patients presented with paraplegia and sensory, bladder, and rectal disturbances. Thoracic magnetic resonance imaging showed longitudinal high-intensity signals on a T2-weighted image. The patients received high-dose methylprednisolone. Their serum was positive for anti-AQP4 antibody (cell-based assay) during the clinical course. They were diagnosed with NMOSD and treated with immunoadsorption, plasmapheresis, and followed up with daily prednisolone. Very-late-onset NMOSD in patients over the age of 80 has only rarely been reported. The present cases suggest that NMOSD should be considered for elderly patients presenting with transverse myelitis. Early diagnosis and treatment are important.

scholarly journals Metabolomic Profiling in Neuromyelitis Optica Spectrum Disorder Biomarker Discovery

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 374
Author(s):  
Maxton E. Thoman ◽  
Susan C. McKarns
Keyword(s):  
Neuromyelitis Optica ◽  
Biomarker Discovery ◽  
Clinical Symptoms ◽  
Water Channel ◽  
Short Chain Fatty Acids ◽  
Spectrum Disorder ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Specific Test ◽  
Metabolomic Profiling ◽  
The Central Nervous System

There is no specific test for diagnosing neuromyelitis optica spectrum disorder (NMOSD), a disabling autoimmune disease of the central nervous system. Instead, diagnosis relies on ruling out other related disorders with overlapping clinical symptoms. An urgency for NMOSD biomarker discovery is underscored by adverse responses to treatment following misdiagnosis and poor prognosis following the delayed onset of treatment. Pathogenic autoantibiotics that target the water channel aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) contribute to NMOSD pathology. The importance of early diagnosis between AQP4-Ab+ NMOSD, MOG-Ab+ NMOSD, AQP4-Ab− MOG-Ab− NMOSD, and related disorders cannot be overemphasized. Here, we provide a comprehensive data collection and analysis of the currently known metabolomic perturbations and related proteomic outcomes of NMOSD. We highlight short chain fatty acids, lipoproteins, amino acids, and lactate as candidate diagnostic biomarkers. Although the application of metabolomic profiling to individual NMOSD patient care shows promise, more research is needed.

Pregnancy-related relapse risk factors in women with anti-AQP4 antibody positivity and neuromyelitis optica spectrum disorder

2016 ◽  
Vol 22 (11) ◽  
pp. 1413-1420 ◽  
Author(s):  
Yuko Shimizu ◽  
Kazuo Fujihara ◽  
Takashi Ohashi ◽  
Ichiro Nakashima ◽  
Kazumasa Yokoyama ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Neuromyelitis Optica ◽  
Spectrum Disorder ◽  
Low Doses ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Annualized Relapse Rate ◽  
Antibody Positivity ◽  
Aqp4 Antibody

Background: Few reports describe the influence pregnancy has on the annualized relapse rate (ARR) in neuromyelitis optica spectrum disorder (NMOSD). Objective: To examine pregnancy-related attacks (attacks during pregnancy or within 1 year postpartum) and identify the risk factors for an attack in Japanese NMOSD patients. Methods: We retrospectively reviewed 139 Japanese women whom had aquaporin-4 (AQP4) antibody-positive NMOSD. Among the 114 patients with information, 47 women had 56 pregnancies. We compared the ARR before, during and after pregnancy. Results: Of the 47 NMOSD patients with pregnancy, 22 women (46.8%) had a pregnancy-related attack of the disease (either an onset event or a relapse). The ARR was significantly higher in the first 3 months postpartum (1.80 ± 2.04), than before the pregnancy (0.57 ± 1.16; p = 0.0043) and did not significantly decrease during pregnancy. The ARR before hospitalization and treatment was analyzable in 55 patients without pregnancy and was 1.09 ± 1.17. Among the 11 patients with onset before pregnancy, nine patients had a pregnancy-related attack with a relapse in the previous year, and their immunosuppression was discontinued or made to be at low doses; while the two patients on higher-dose therapies were relapse-free. Conclusion: In the present study, pregnancy-related attack was common in NMOSD, and unlike in multiple sclerosis, the ARR was not reduced during pregnancy. Discontinued or insufficient immunosuppression appeared to increase the risk of pregnancy-related attack.

Association of cigarette smoking with neuromyelitis opticaimmunoglobulin G sero-positivity in neuromyelitis optica spectrum disorder

2019 ◽  
Author(s):  
Sharareh Eskandarieh ◽  
Abdorreza Naser Moghadasi ◽  
Mohammad Ali Sahraiain ◽  
Amir Reza Azimi ◽  
Negar Molazadeh
Keyword(s):  
Cigarette Smoking ◽  
Neuromyelitis Optica ◽  
Demyelinating Disease ◽  
Water Channel ◽  
Cross Sectional Study ◽  
Spectrum Disorder ◽  
Enzyme Linked Immunosorbent Assay ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Cross Sectional ◽  
Tertiary Referral Center

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a neuroinflammatory demyelinating disease caused by the presence of a highly specific serum autoantibody marker, NMO-immunoglobulin G (NMO-IgG), that reacts against the water channel aquaporin-4 (AQP4). The present study examined the association between NMO-IgG sero-positivity and environmental factors such as cigarette smoking. Methods: A cross-sectional study was conducted in Sina Hospital, a tertiary referral center in Tehran, Iran. All the patients with a definite diagnosis of NMOSD were involved in this study. The enzyme-linked immunosorbent assay (ELISA) was used to examine the AQP4-IgG status. To assess the association between NMO-IgG sero-positivity and cigarette smoking, a researcher-made questionnaire covering patients’ lifestyle information on smoking habits was designed and administered using the structured face-to-face interviews with the patients. Results: The positive and negative NMO-IgG results were found in 44 (46.8%) and 50 (53.2%) patients, respectively. The increased NMO-IgG sero-positivity odds were observed among the lifetime smokers [odds ratio (OR) = 3.24, 95% confidence interval (CI): 1.16-9.08], current smokers (OR = 6.08, 95% CI: 1.26-29.39), and passive smokers (OR = 2.22, 95% CI: 1.10-4.50). Conclusion: Lifetime and current smoking as well as passive smoking can be regarded as risk factors for NMO-IgG sero-positivity. Smoking with its immunological effects can lead to the production of autoantibodies such as NMO-IgG. 

scholarly journals Two Cases of Pediatric AQP4-Antibody Positive Neuromyelitis Optica Spectrum Disorder Successfully Treated with Tocilizumab

2019 ◽  
Vol 50 (03) ◽  
pp. 193-196
Author(s):  
Markus Breu ◽  
Sarah Glatter ◽  
Romana Höftberger ◽  
Michael Freilinger ◽  
Karl Kircher ◽  
...  
Keyword(s):  
B Cell ◽  
Neuromyelitis Optica ◽  
Spectrum Disorder ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Interleukin 6 Receptor ◽  
Anti Cd20 ◽  
Aqp4 Antibody

AbstractB cell depletion with the anti-CD20-antibody rituximab is widely considered treatment of choice for long-term immunotherapy in aquaporin-4 (AQP4)-antibody positive neuromyelitis optica spectrum disorder (NMOSD). However, up to 30% of patients suffer from relapses despite complete B cell depletion. In these cases, the IL6 (interleukin-6)-receptor blocking antibody tocilizumab has been suggested as an alternative. We report two female adolescents with AQP4-antibody positive NMOSD who relapsed under rituximab treatment and clinically stabilized after switching to monthly administrations of tocilizumab. Our data suggest that early escalation of therapy with tocilizumab may lead to stabilization of disease activity in pediatric NMOSD patients who relapse under B cell depletion.

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