scholarly journals Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG–Associated Disease and Neuromyelitis Optica Spectrum Disorders

2021 ◽  
Vol 9 (1) ◽  
pp. e1100
Author(s):  
Marius Ringelstein ◽  
Ilya Ayzenberg ◽  
Gero Lindenblatt ◽  
Katinka Fischer ◽  
Anna Gahlen ◽  
...  
Keyword(s):  
Neuromyelitis Optica ◽  
Interleukin 6 ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Class Iii ◽  
Disability Status ◽  
Interleukin 6 Receptor ◽  
Spectrum Disorders ◽  
The Brain

Background and ObjectivesTo evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti–interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein–IgG–associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD).MethodsAnnualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab.ResultsPatients received TCZ for 23.8 months (median; interquartile range 13.0–51.1 months), with an IV dose of 8.0 mg/kg (median; range 6–12 mg/kg) every 31.6 days (mean; range 26–44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5–5) to 0 (range 0–0.9; p = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0–5] to 0 [range 0–4.2]; p < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0–3.0] to 0.2 [range 0–2.0]; p = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD (p = 0.04; for the brain) and in AQP4-IgG+ NMOSD (p < 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy.DiscussionThis study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD.

Atypical myelitis in patients with multiple sclerosis: Characterization and comparison with typical multiple sclerosis and neuromyelitis optica spectrum disorders

2020 ◽  
pp. 135245852090699
Author(s):  
K Bigaut ◽  
C Lambert ◽  
L Kremer ◽  
C Lebrun ◽  
M Cohen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Transverse Myelitis ◽  
First Episode ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Disability Status ◽  
Plane Transverse ◽  
Spectrum Disorders ◽  
Extensive Transverse Myelitis

Background: Atypical myelitis in multiple sclerosis (MS) is characterized by extensive myelitis in the longitudinal (longitudinally extensive transverse myelitis) or axial plane (transverse myelitis). Objective: To characterize a cohort of MS patients with atypical myelitis. Methods: Atypical myelitis was extracted from the French and Luxembourg MS databases and compared to two cohorts of MS patients with typical myelitis and neuromyelitis optica spectrum disorders (NMOSDs) patients with myelitis. Results: We enrolled 28 MS patients with atypical myelitis, 68 MS patients with typical myelitis and 119 NMOSD patients with a first episode of myelitis. MS patients with atypical myelitis were characterized by a mean age of 34.0 (±10.7) years and 64.3% were women. In 82.1% of the patients, atypical myelitis was the first episode of MS. Mean Expanded Disability Status Scale (EDSS) scores at nadir and 3–6 months after onset were 4.1 ± 2.1 and 3.3 ± 2, respectively. Differences between groups revealed a predominance of cervicothoracic myelitis and a higher level of disability in NMOSD patients. Disability in MS patients with atypical myelitis was more severe than in the MS patients with typical myelitis; 28% had already converted to progressive MS within our mean follow-up of 39.6 (±30.4) months. Conclusion: Atypical myelitis may be the first presentation of MS and is associated with poorer prognosis.

Neuromyelitis optica spectrum disorders: long-term safety and efficacy of rituximab in Caucasian patients

2015 ◽  
Vol 22 (4) ◽  
pp. 511-519 ◽  
Author(s):  
M Radaelli ◽  
L Moiola ◽  
F Sangalli ◽  
F Esposito ◽  
V Barcella ◽  
...  
Keyword(s):  
Adverse Events ◽  
Neuromyelitis Optica ◽  
Close Monitoring ◽  
Disability Status ◽  
Caucasian Patients ◽  
Spectrum Disorders ◽  
High Level ◽  
Term Benefit

Objective: To assess the long-term benefit-risk profile of repeated courses of rituximab in Caucasian patients affected by neuromyelitis optica (NMO) and related disorders, in everyday clinical practice. Methods: This is a prospective observational study performed at San Raffaele Hospital, Milan, Italy. From February 2006, we recruited 21 patients affected by NMO and NMO spectrum of disorders (NMOSD) whom underwent at least one cycle of intravenous (i.v.) rituximab and then were followed for at least 2 years. Results: At a mean follow-up time of 48 months, we observed a significant reduction of the annualized relapse rate (ARR), from 2.0 to 0.16 ( p < 0.01); and of the median Expanded Disability Status Scale (EDSS), from 5.5 to 4.0 ( p < 0.013). There were 12 patients (57%) who remained disease free during the follow-up period. Five patients (24%) reported mild hematological adverse events. Serious infectious adverse events were reported by another four patients: These were all wheelchair bound at the beginning of their rituximab treatment. Conclusions: A fixed treatment scheme of rituximab, with re-treatment every 6 months, was efficacious for NMO and NMOSD, with a good safety profile; however, to obtain an even better benefit-risk ratio, close monitoring of CD19+ B cells should be performed before the re-treatment of patients with high-level disability, concomitant leukopenia and hypogammaglobulinemia.

Early predictors of disability of paediatric-onset AQP4-IgG-seropositive neuromyelitis optica spectrum disorders

2021 ◽  
pp. jnnp-2021-327206
Author(s):  
Valentina Camera ◽  
Silvia Messina ◽  
Kariem Tarek Elhadd ◽  
Julia Sanpera-Iglesias ◽  
Romina Mariano ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Neuromyelitis Optica ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Onset Age ◽  
Visual Disability ◽  
Therapeutic Decisions ◽  
First Relapse ◽  
Edss Score ◽  
Spectrum Disorders

ObjectiveTo describe onset clinical features predicting time to first relapse and time to long-term visual, motor and cognitive disabilities in paediatric-onset aquaporin-4 antibody (AQP4-IgG) neuromyelitis optica spectrum disorders (NMOSDs).MethodsIn this retrospective UK multicentre cohort study, we recorded clinical data of paediatric-onset AQP4-IgG NMOSD. Univariate and exploratory multivariable Cox proportional hazard models were used to identify long-term predictors of permanent visual disability, Expanded Disability Status Scale (EDSS) score of 4 and cognitive impairment.ResultsWe included 49 paediatric-onset AQP4-IgG patients (38.8% white, 34.7% black, 20.4% Asians and 6.1% mixed), mean onset age of 12±4.1 years, and 87.7% were female. Multifocal onset presentation occurred in 26.5% of patients, and optic nerve (47%), area postrema/brainstem (48.9%) and encephalon (28.6%) were the most involved areas. Overall, 52.3% of children had their first relapse within 1 year from disease onset. Children with onset age <12 years were more likely to have an earlier first relapse (p=0.030), despite showing no difference in time to immunosuppression compared with those aged 12–18 years at onset. At the cohort median disease duration of 79 months, 34.3% had developed permanent visual disability, 20.7% EDSS score 4 and 25.8% cognitive impairment. Visual disability was associated with white race (p=0.032) and optic neuritis presentations (p=0.002). Cognitive impairment was predicted by cerebral syndrome presentations (p=0.048), particularly if resistant to steroids (p=0.034).ConclusionsAge at onset, race, onset symptoms and resistance to acute therapy at onset attack predict first relapse and long-term disabilities. The recognition of these predictors may help to power future paediatric clinical trials and to direct early therapeutic decisions in AQP4-IgG NMOSD.

Cytokines and Tissue Damage Biomarkers in First-Onset Neuromyelitis Optica Spectrum Disorders: Significance of Interleukin-6

2018 ◽  
Vol 25 (4) ◽  
pp. 215-224 ◽  
Author(s):  
Yuzhen Wei ◽  
Haoxiao Chang ◽  
Xindi Li ◽  
Huabing Wang ◽  
Li Du ◽  
...  
Keyword(s):  
Neuromyelitis Optica ◽  
Interleukin 6 ◽  
Tissue Damage ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
First Onset ◽  
Spectrum Disorders

scholarly journals Differences in clinical features between optic neuritis in neuromyelitis optica spectrum disorders and in multiple sclerosis

2018 ◽  
Vol 4 (3) ◽  
pp. 205521731879119 ◽  
Author(s):  
Jindapa Srikajon ◽  
Sasitorn Siritho ◽  
Chanon Ngamsombat ◽  
Naraporn Prayoonwiwat ◽  
Niphon Chirapapaisan ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Visual Acuity ◽  
Optic Neuritis ◽  
Neuromyelitis Optica ◽  
Retrospective Chart Review ◽  
Visual Outcome ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Fiber Layer ◽  
Spectrum Disorders

Background Optic neuritis (ON) is one of the common manifestations both in neuromyelitis-optica spectrum disorders (NMOSD) and in multiple sclerosis (MS). Objectives The objective of this paper is to compare clinical presentations, laboratories and imaging findings in ON associated with MS and NMOSD. Methods A retrospective chart review was performed in patients presenting with ON in 59 NMOSD patients with 72 eyes’ involvement and 163 ON attacks, and 20 MS patients with 23 eyes’ involvement and 36 ON attacks. Results ON-NMOSD patients had recurrent ON more often and tended to have simultaneous bilateral ON involvement at their first ON attack. Individuals with ON-NMOSD revealed worse visual acuity at first ON attacks and also had poorer long-term visual outcome than those with ON-MS, with nearly half of ON-NMOSD patients still having LogMAR visual acuity ≥1 at their last follow-up ( p = 0.035). Significant thinner average retinal nerve fiber layer thickness was found in the ON-NMOSD group. We found no significant differences in segmentation location of the optic nerve lesions and the length of involvement between the two groups. Conclusions It was difficult to completely differentiate ON-NMOSD from ON-MS. ON-NMOSD patients, however, tended to have simultaneous bilateral ON involvement and poorer long-term visual outcome than individuals with ON-MS.

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