Recent progress in maintenance treatment of neuromyelitis optica spectrum disorder

Holmøy, Trygve; Høglund, Rune Alexander; Illés, Zsolt; Myhr, Kjell Morten; Torkildsen, Øivind

doi:10.1007/s00415-020-10235-5

Cited by 43 publications

(48 citation statements)

References 149 publications

(190 reference statements)

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“…According to our current knowledge, DMTs could predispose MS patients to a higher risk of either community-acquired or opportunistic infections ( Grebenciucova and Pruitt, 2017 ; Luna et al, 2020 ). Traditional immunosuppressive treatments and the emerging NMOSD treatments are also associated with an increased risk of infections (viral and bacterial) ( Holmoy et al, 2020 ). Based on this background, it would be reasonable to hypothesize that these therapies may increase the risk of COVID-19 infection predisposing towards a severe infection and worse outcomes ( Brownlee et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

COVID-19 in multiple sclerosis and neuromyelitis optica spectrum disorder patients in Latin America

Alonso

Silva²,

Garcea³

et al. 2021

Multiple Sclerosis and Related Disorders

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Background There is no data regarding COVID-19 in Multiple Sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients in Latin America. Objective The objective of this study was to describe the clinical characteristics and outcomes of patients included in RELACOEM, a LATAM registry of MS and NMOSD patients infected with COVID-19. Methods RELACOEM is a longitudinal, strictly observational registry of MS and NMOSD patients who suffer COVID-19 and Dengue in LATAM. Inclusion criteria to the registry were either: (1) a biologically confirmed COVID-19 diagnosis based on a positive result of a COVID-19 polymerase chain reaction (PCR) test on a nasopharyngeal swab; or (2) COVID-19–typical symptoms (triad of cough, fever, and asthenia) in an epidemic zone of COVID-19. Descriptive statistics were performed on demographic and clinical variables. The cohort was later stratified for MS and NMOSD and univariate and multivariate logistic regression analysis was performed to identify variables associated with hospitalizations/intensive critical units (ICU) admission. Results 145 patients were included in the registry from 15 countries and 51 treating physicians. A total of 129 (89%) were MS patients and 16 (11%) NMOSD. 81.4% patients had confirmed COVID-19 and 18.6% were suspected cases. 23 (15.8%) patients were hospitalized, 9 (6.2%) required ICU and 5 (3.4 %) died due to COVID-19. In MS patients, greater age (OR 1.17, 95% CI 1.05 – 1.25) and disease duration (OR 1.39, 95%CI 1.14-1.69) were associated with hospitalization/ICU. In NMOSD patients, a greater age (54.3 vs. 36 years, p=<0.001), increased EDSS (5.5 vs 2.9, p=0.0012) and disease duration (18.5 vs. 10.3 years, p=0.001) were significantly associated with hospitalization/ICU. Conclusion we found that in MS patients, age and disease duration was associated with hospitalization and ICU admission requirement, while age, disease duration and EDSS was associated in NMOSD.

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Section: Introductionmentioning

confidence: 99%

COVID-19 in multiple sclerosis and neuromyelitis optica spectrum disorder patients in Latin America

Alonso

Silva²,

Garcea³

et al. 2021

Multiple Sclerosis and Related Disorders

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“…The pathogenic role of NMO-IgG in the presence of human complement is also supported by the results of passive transfer experiments ( 5 , 21 ) and in vivo disease models, where complement inhibition was proven to be beneficial ( 24 ). Moreover, clinical experience also sustains the role of complement activation in disease pathogenesis, since treatment with the monoclonal anti-C5 antibody eculizumab reduced attack frequency, and stabilized or improved neurological disability of patients with NMOSD ( 25 , 26 ). Thus, therapeutic complement inhibition is a promising strategy in the treatment of NMOSD ( 24 , 27 ), and eculizumab has been approved for treating AQP4-IgG positive NMOSD.…”

Section: Introductionmentioning

confidence: 84%

Autoantibodies Against the Complement Regulator Factor H in the Serum of Patients With Neuromyelitis Optica Spectrum Disorder

et al. 2021

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Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system (CNS), characterized by pathogenic, complement-activating autoantibodies against the main water channel in the CNS, aquaporin 4 (AQP4). NMOSD is frequently associated with additional autoantibodies and antibody-mediated diseases. Because the alternative pathway amplifies complement activation, our aim was to evaluate the presence of autoantibodies against the alternative pathway C3 convertase, its components C3b and factor B, and the complement regulator factor H (FH) in NMOSD. Four out of 45 AQP4-seropositive NMOSD patients (~9%) had FH autoantibodies in serum and none had antibodies to C3b, factor B and C3bBb. The FH autoantibody titers were low in three and high in one of the patients, and the avidity indexes were low. FH-IgG complexes were detected in the purified IgG fractions by Western blot. The autoantibodies bound to FH domains 19-20, and also recognized the homologous FH-related protein 1 (FHR-1), similar to FH autoantibodies associated with atypical hemolytic uremic syndrome (aHUS). However, in contrast to the majority of autoantibody-positive aHUS patients, these four NMOSD patients did not lack FHR-1. Analysis of autoantibody binding to FH19-20 mutants and linear synthetic peptides of the C-terminal FH and FHR-1 domains, as well as reduced FH, revealed differences in the exact binding sites of the autoantibodies. Importantly, all four autoantibodies inhibited C3b binding to FH. In conclusion, our results demonstrate that FH autoantibodies are not uncommon in NMOSD and suggest that generation of antibodies against complement regulating factors among other autoantibodies may contribute to the complement-mediated damage in NMOSD.

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“…Though, IL-6 inhibitors have established themselves as an important class of monoclonal antibodies in the eld of treatment of relapses of NMOSD, the road ahead is long, as the bene ts are only applicable to a large subset of AQP4-Ab seropositive patients leaving behind the important hurdle to nd a drug that can impact the disease course of AQP-4 Ab seronegative groups. 10 Our meta-analysis has several strengths. We have systematically collected all evidence including real-world data and RCTs for the e cacy and safety of IL-6 inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…are being widely used and studied. 10 IL-6 inhibitors like Tocilizumab and Satralizumab, are now being considered as good options for treatment of NMO/NMOSD and potential therapeutic effects of two anti-IL-6 agents Tocilizumab and Satralizumab have been investigated via clinical trials and have shown promising results in the treatment of active NMOSD case, however, summarized data is lacking. 11 To establish IL-6 inhibitors drugs as e cacious and tolerated treatment options in the management of NMO/NMOSD, this meta-analysis is done with the aim of nding the combined effect size of their e cacy and safety from real-world studies.…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of IL-6 Inhibitors in the Treatment of Neuromyelitis Optica Spectrum Disorders. A Meta-analysis

Kharel

Shrestha

Ojha

et al. 2021

Preprint

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BackgroundInterleukin-6 (IL-6) inhibitors like Tocilizumab and Satralizumab are showing promising results in the treatment of Neuromyelitis Optica spectrum disorder (NMOSD). We aimed to investigate the efficacy and safety of various IL-6 inhibitors in the management of NMO/NMOSD.MethodsPubMed, Embase, and The Cochrane Library were systematically searched for suitable studies. Change in Annualized Relapse Ratio (ARR), Change in Extended Disability Status Scale (EDSS) s, the proportion of relapse-free patients, on trial relapse risk, and proportion of patients with adverse events, including serious adverse events and mortality were the parameters considered for the meta-analysis. Mean difference (MD) with 95% CI was used to quantify the change in ARR and change in EDSS-before and after treatment. While pooled risk ratio between the intervention group and placebo group was used in Randomized Controlled Trial (RCTs). A forest plot was prepared to indicate the efficacy outcomes.Results A total of nine studies with 202 patients were included in our meta-analysis. IL-6 inhibitors found a good proportion (75%,95% CI: 0.62–0.89; p<0.001) of relapse free patients at follow up. It also significantly reduced mean ARR (mean difference: -2.6 95% CI: -2.71 to -1.68; p<0.001) and on trial relapse risk (RR: 0.46; 95% CI: 0.32‐0.66; P< 0.001) but did not show significant difference in change in EDSS score (mean difference=-0.79, 95% CI: -1.89 to -0.31; p=0.16). Also, the toxicity profile of IL-6 inhibitors was acceptable considering the proportions of patients with adverse events (72%, 95% C.I.;0.59-0.84, I2=85.29%, p<0.001), proportions of patients with serious adverse events (18%;95% C.I.; -3.68 to 4.04, I2=0%, p=0.93) and zero treatment related deaths. In subgroup analysis, we found subcutaneous administration to be superior (81%;95% CI:0.74-0.82) than intravenous route (67%; 95% CI:0.67-0.89) in relapse free maintenance.ConclusionIL-6 inhibitor therapy showed significant benefits in reducing mean ARR, relapse risk and increasing the number of relapse-free patients with acceptable adverse events profile.

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Recent progress in maintenance treatment of neuromyelitis optica spectrum disorder

Cited by 43 publications

References 149 publications

COVID-19 in multiple sclerosis and neuromyelitis optica spectrum disorder patients in Latin America

COVID-19 in multiple sclerosis and neuromyelitis optica spectrum disorder patients in Latin America

Autoantibodies Against the Complement Regulator Factor H in the Serum of Patients With Neuromyelitis Optica Spectrum Disorder

Safety and Efficacy of IL-6 Inhibitors in the Treatment of Neuromyelitis Optica Spectrum Disorders. A Meta-analysis

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