Safety and efficacy of inebilizumab for the treatment of neuromyelitis optica spectrum disorder: end-of-study results from the open-label period of the N-MOmentum trial.

BACKGROUND: Inebilizumab, an anti-CD19 B-cell-depleting antibody, demonstrated safety and efficacy in neuromyelitis optica spectrum disorder in the randomised controlled period of the N-MOmentum trial. Here, end-of-study data, including the randomised controlled period and open-label extension period, are reported. METHODS: In the double-blind, randomised, placebo-controlled, phase 2/3 N-MOmentum trial, adults aged 18 years and older with an neuromyelitis optica spectrum disorder diagnosis, Expanded Disability Status Scale score of 8·0 or less, and history of either at least one acute inflammatory attack requiring rescue therapy in the past year or two attacks requiring rescue therapy in the past 2 years, were recruited from 81 outpatient specialty clinics or hospitals in 24 countries. Eligible participants were randomly assigned (3:1), using a central interactive voice system or interactive web response system, and a permuted block randomisation scheme (block size of 4), to receive intravenous inebilizumab (300 mg) or identical placebo on days 1 and 15 of the randomised period, which lasted up to 197 days. Participants and all study staff were masked to treatment assignment. The primary endpoint of the randomised period of the trial was time to onset of adjudicated neuromyelitis optica spectrum disorder attack on or before day 197. Participants in the randomised controlled period who had an adjudicated attack, completed 197 days in the study, or were in the randomised controlled period when enrolment stopped, could voluntarily enter the open-label period. In the open-label period, participants either initiated inebilizumab if assigned placebo (receiving 300 mg on days 1 and 15 of the open-label period) or continued treatment if assigned inebilizumab (receiving 300 mg on day 1 and placebo on day 15, to maintain B-cell depletion and masking of the randomised controlled period). All participants subsequently received inebilizumab 300 mg every 6 months for a minimum of 2 years. The end-of-study analysis endpoints were time to adjudicated attack and annualised attack rate (assessed in all participants who received inebilizumab at any point during the randomised controlled period or open-label period [any inebilizumab population] and the aquaporin-4 [AQP4]-IgG seropositive subgroup [any inebilizumab-AQP4-IgG seropositive population]) and safety outcomes (in all participants who were exposed to inebilizumab, analysed as-treated). This study is registered with ClinicalTrials.gov, NCT02200770, and is now complete. FINDINGS: Between Jan 6, 2015, and Sept 24, 2018, 467 individuals were screened, 231 were randomly assigned, and 230 received at least one dose of inebilizumab (n=174) or placebo (n=56). Between May 19, 2015, and Nov 8, 2018, 165 (95%) of 174 participants in the inebilizumab group and 51 (91%) of 56 in the placebo group entered the open-label period (mean age 42·9 years [SD 12·4], 197 [91%] of 216 were female, 19 [9%] were male, 115 [53%] were White, 45 [21%] were Asian, 19 [9%] were American Indian or Alaskan Native, and 19 [9%] were Black or African American). As of data cutoff for this end of study analysis (Dec 18, 2020; median exposure 1178 days [IQR 856-1538], total exposure of 730 person-years) 225 participants formed the any inebilizumab population, and 208 (92%) participants were AQP4-IgG seropositive. Overall, 63 adjudicated neuromyelitis optica spectrum disorder attacks occurred in 47 (21%) of 225 treated participants (60 attacks occurred in 44 [21%] of 208 in the AQP4-IgG seropositive subgroup); 40 (63%) of 63 attacks occurred in 34 (15%) of 225 treated participants during the first year of treatment. Of individuals who had an adjudicated attack while receiving inebilizumab, 36 (77%) of 47 were subsequently attack-free at the end of 4 years. Annualised attack rates decreased year-on-year, with end-of-study adjusted annualised attack rates being similar in the any inebilizumab-AQP4-IgG seropositive subgroup (0·097 [95% CI 0·070-0·14]) and any inebilizumab populations (0·092 [0·067-0·13]). Overall, 208 (92%) of 225 participants who received any inebilizumab had at least one treatment-emergent adverse event, the most frequent of which were urinary tract infection (59 [26%]), nasopharyngitis (47 [21%]), and arthralgia (39 [17%]). Infection rates did not increase over 4 years. Three (1%) of 225 participants in the any inebilizumab population died during the open-label period (one each due to a CNS event of unknown cause and pneumonia, respiratory insufficiency resulting from an neuromyelitis optica spectrum disorder attack and viral pneumonia related to COVID-19), all of which were deemed to be unrelated to treatment. INTERPRETATION: Data from the end-of-study analysis of the N-MOmentum trial showed continued and sustained clinical benefits of long-term inebilizumab treatment in individuals with neuromyelitis optica spectrum disorder, which supports the role of inebilizumab as a CD19+ B-cell-depleting therapy in neuromyelitis optica spectrum disorder. FUNDING: MedImmune and Viela Bio/Horizon Therapeutics, now part of Amgen.

FCGR3A-V158F gene polymorphism: A potential predictor for rituximab dosing optimization in Chinese patients with neuromyelitis optica spectrum disorder.

BACKGROUND: Rituximab (RTX), an anti-CD20 monoclonal antibody, has shown promise in managing neuromyelitis optica spectrum disorders (NMOSD) by depleting B cells and reducing relapses. However, there is no consensus on the optimal RTX dosing regimen, and genetic factors, such as FCGR3A-V158F polymorphism, may influence treatment outcomes. This study investigates how FCGR3A-V158F genotypes influence RTX efficacy in Chinese NMOSD patients under varying dosing regimens and aims to optimize treatment protocols. METHODS: We conducted a retrospective analysis of 25 Chinese NMOSD patients treated with RTX, grouped into standardized and low-dosage regimens. FCGR3A-V158F genotypes were determined, and treatment responses were evaluated, including relapse rates, time to first relapse (TFR), B-cell depletion, dose adjustments, and treatment retention. RESULTS: Among all patients, 15 received standardized dosages, while 10 received varied induction doses (500 mg to 1200 mg) in low-dose regimens. For FCGR3A-V158F genotypes, 15 had the FF genotype, and 10 were V carriers (3 VV genotype, 7 VF genotype). Regardless of dosing, FF genotype patients had a higher relapse rate post-RTX treatment compared to V carriers (P < 0.05). None of the 3 VV genotype patients in either dose group experienced relapses post-RTX. In both dose groups, FF genotype patients had significantly shorter TFR and required more RTX dose adjustments post-RTX treatment compared to V carriers in the standardized dosage group (P < 0.05). FF genotype patients in the low dosage group were more likely to experience insufficient B-cell depletion, had lower treatment retention rates, and more discontinuations than V carriers in the standardized dosage group (P < 0.05). Insufficient B-cell depletion significantly predicted clinical relapses after RTX treatment (P < 0.05). In survival analysis, FF genotype patients, regardless of dosing, experienced earlier relapses post-RTX treatment (P < 0.05). CONCLUSIONS: This study highlights the importance of RTX dosage selection in NMOSD treatment, particularly for FCGR3A-FF genotype patients. Standard-dose RTX therapy with vigilant monitoring of peripheral blood B-cell levels is recommended for these individuals to optimize treatment efficacy.

Rituximab-induced gut microbiota changes in Chinese neuromyelitis optica spectrum disorders.

BACKGROUND: Recent evidence shows that immunosuppressive agents can affect the gut microbiota in autoimmune diseases. However, the relationship between the gut microbiome and B-cell depletion immunotherapy in neuromyelitis optica spectrum disorder (NMOSD) remains poorly understood. OBJECTIVES: To evaluate the distinct intestinal microbial patterns and serum cytokine levels after short-term rituximab treatment (three months) in patients with NMOSD. METHODS: Firstly, we conducted a cross-sectional study involving 46 treatment-naïve NMOSD patients and 48 matched healthy controls. We collected fecal specimens, which were then analyzed using next-generation sequencing, and quantified serum cytokines. Subsequently, fecal and serum samples were re-collected and re-evaluated in 31 of the 46 treatment-naïve NMOSD patients after RTX treatment. RESULTS: Comparing the gut microbiome of treatment-naïve NMOSD patients to that of healthy controls revealed low α-diversity and distinct microbial compositions in the former. The microbial composition in NMOSD patients underwent changes following three months of RTX treatment. Specifically, the levels of IL-17F and IL-6 decreased, while those of IL-10 and TNFα increased after RTX treatment. LEfSe analysis identified 27 KEGG categories with significantly differential abundances between NMOSD patients and RTX treatment group. CONCLUSIONS: Our study provides a comprehensive understanding of the gut microbiota landscape in the context of B-cell depletion immunotherapy. We observed dysbiosis in the gut microbiome of NMOSD patients, which was partially alleviated by three months of RTX treatment. This suggests that B-cell depletion may play a crucial role in driving changes in the gastrointestinal environment.

Effectiveness of tixagevimab/cilgavimab (Evusheld) in antiCD20­treated patients with multiple sclerosis and neuromyelitis optica spectrum disorder.

BACKGROUND: AntiCD20 therapy, such as rituximab, ocrelizumab, or ofatumumab, effectively treats patients with multiple sclerosis (pwMS) or neuromyelitis optica spectrum disorder (pwNMOSD) but negatively affects the humoral immune response to COVID-19 vaccination. One strategy to protect these patients is using tixagevimab/cilgavimab (T/C) as pre-exposure prophylaxis. This study aimed to evaluate the effect of T/C on the incidence of COVID-19 in pwMS and pwNMOSD. METHODS: Data in this observational cohort study were collected in two Czech MS centres through ReMuS registry between March 1, 2020 and December 31, 2022. Adult pwMS and pwNMOSD who were (1) treated with antiCD20 therapy at least six months before T/C administration, or at least from February 1, 2022 in the control group; (2) were already on antiCD20 therapy at the time of vaccination or COVID-19 infection; and (3) were on antiCD20 therapy at least 100 days after T/C, or at least 90 days after August 1, 2022 in the control group, were included. Analysis was performed using frequency-based (propensity score matching) and Bayesian statistical methods (informative and non-informative priors). RESULTS: Using propensity score matching 1:1, 47 patients who received T/C (mean age 45.7 years, median disease duration 12.5 years) were matched with those who did not receive T/C (n = 341; mean age 46.6 years, median disease duration 11.4 years) based on age, MS/NMOSD duration, and number of vaccine doses. None of the T/C patients and three in the control matched group, developed COVID-19 between 10 and 100 days after receiving T/C, August 1, 2022, respectively. The frequency of COVID-19 was not significantly different between groups (p = 0.242). Due to the low number of patients, a Bayesian analysis was also added. Using a non-informative Bayesian prior, the median relative risk of COVID-19 after T/C was 7.6 % (95 % CrI 0.02-115.9 %). The posterior probability of risk difference lower than zero was 96.4 %. Using an informative prior (based on the registration study of Evusheld), the median relative risk of COVID-19 after T/C was 20.2 % (95 % CI 8.4-43.8 %). The posterior probability of the risk difference lower than zero was 100 %. CONCLUSION: This work highlights the possible good efficacy of T/C in antiCD20-treated pwMS and pwNMSOD. Based on Bayesian analysis with an informative prior, the T/C group's risk of COVID-19 infection was approximately 20.2 % of the control group's risk. However, given the low frequency of COVID-19, the results of this pilot analysis must be interpreted with caution.

Case report: Identification of Hepatitis B Virus in the cerebrospinal fluid of neuromyelitis optica spectrum disorders and successful treatment with ofatumumab and inebilizumab.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare demyelinating disease of the central nervous system primarily affecting the optic nerves, spinal cord, and brainstem. Viral infection may trigger NMOSD. Here, we report the case of a 34-year-old female presenting with a range of symptoms including nausea, vomiting, dysphagia, choking, and fatigue with unsteady gait, diplopia, hearing loss, left-sided facial paralysis, breathing difficulties, and hoarseness of voice. Her HBV DNA concentration, as determined by quantitative PCR analysis, exceeded 5×107 IU/ml in serum and 4.48×102 IU/ml in CSF. Next-generation sequencing of CSF revealed 1,528 HBV sequences in DNA analysis and 6 sequences in RNA analysis. Serum aquaporin-4 antibody (AQP4-Ab) titer was 1:10, and the CSF titer was 1:3.2. Brain magnetic resonance imaging showed high signal intensities in the brain stem, medulla oblongata, and left middle cerebellar peduncle with mild restricted-diffusion. The patient received antiviral and hepatoprotective medications before the high-dose methylprednisolone pulse therapy. However, the patient did not respond well to the first-line treatment. Subsequently, the patient received ofatumumab and inebilizumab. Throughout the follow-up period, there was a gradual improvement in her neurological symptoms, with no reactivation of hepatitis B or deterioration of liver function observed. Thereby, to the best of our knowledge, we report the first case of successful treatment with ofatumumab and inebilizumab in a patient with NMOSD concurrent with HBV infection.

Impact of rituximab treatment regime on time to relapse in aquaporin-4 antibody positive neuromyelitis optica spectrum disorder.

BACKGROUND: Aquaporin-4 (AQP4) antibody associated neuromyelitis optica (NMOSD) requires long-term immunosuppression. Rituximab is increasingly used worldwide, however the optimal regime is not established. METHODS: We retrospectively examined different rituximab regimens in AQP4-NMOSD. Standard monotherapy (SM; 6 monthly infusions), SM plus oral steroids (SM+S), extended interval dosing (EID; guided by CD19 repopulation) and EID with oral steroids (EID+S) were compared. The primary outcome was time to first clinical relapse. Potential confounders including age, gender, number of previous relapses, and onset phenotype were included. RESULTS: 77 patients were included: 67 females, median onset age 35.6, median DSS at rituximab initiation 5.0. 39 were on SM+S, 20 SM, 6 EID, and 12 EID+S. 25/77 patients relapsed during a median follow-up of 44.0 months. No significant difference in time to first relapse was observed between any rituximab regimen. Pooled analyses to compare regimens that use standard monotherapy (SM and SM+S) against those that use extended interval dosing (EID and EID+S) showed no significant difference. Pooled analysis of regimens using steroids with those not using steroids also showed no significant difference. Adjusted Cox proportional hazard model revealed no significant difference between rituximab regimens or influence of demographic factors. 9 significant adverse events were recorded, 5 in the SM group and 4 in SM+S. CONCLUSIONS: This study provides some basis for further exploring EID as a viable option for long term treatment of AQP4-NMOSD. This may improve patient experience and consolidate use of hospital resources.

Role of C5 inhibitors in neuromyelitis optica spectrum disorders with seropositive anti-aquaporin-4 antibody: A systematic review and meta-analysis.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder characterized by relapses of inflammation and demyelination primarily affecting the optic nerve and the spinal cord. C5 complement inhibition is an effective therapeutic approach in the treatment of NMOSD. In this systematic review and meta-analysis, we aimed to determine the role of C5 inhibitors in the treatment of patients with seropositive anti-aquaporin-4 antibody (AQP4+IgG) NMOSD. METHODS: This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Relevant articles were systematically searched through Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases until October 6th, 2023. We included randomized clinical trials (RCTs) that investigated the treatment with C5 inhibitors compared to placebo in patients with seropositive NMOSD. The primary endpoint was the rates of first adjudicated relapse. Secondary endpoints included different disability and quality of life measures. The random-effects model was used for all statistical analyses. RESULTS: Two RCTs with a total of 201 patients were included. C5 inhibitors demonstrated significant reduction of first adjudicated relapse (risk ratio (RR) = 0.05, 95 % CI 0.01-0.15) and Hauser Ambulation Index (HAI) (mean difference (MD): -0.79, 95 % CI -1.27 to -0.31). There was no significant difference between the two groups in Expanded Disability Status Scale (EDSS) (MD -0.23, 95 % CI -0.54-0.08). C5 inhibitors significantly improved the mean change in EQ-5D index (MD 0.08, 95 % CI 0.01-0.14; P = 0.02); however, no significant difference was shown in the mean change in EQ-5D VAS (MD 3.79, 95 % CI -1.61 to 9.19; P = 0.17). Safety measures were comparable between C5 inhibitors and placebo. CONCLUSION: NMOSD Patients with AQP4+IgG receiving C5 inhibitors have lower rate of relapses and improved levels of disability and quality of life. Real-world studies are warranted to establish the long-term safety of C5 inhibitors.

Machine Learning Analysis Using RNA Sequencing to Distinguish Neuromyelitis Optica from Multiple Sclerosis and Identify Therapeutic Candidates.

This study aims to identify RNA biomarkers distinguishing neuromyelitis optica (NMO) from relapsing-remitting multiple sclerosis (RRMS) and explore potential therapeutic applications leveraging machine learning (ML). An ensemble approach was developed using differential gene expression analysis and competitive ML methods, interrogating total RNA-sequencing data sets from peripheral whole blood of treatment-naïve patients with RRMS and NMO and healthy individuals. Pathway analysis of candidate biomarkers informed the biological context of disease, transcription factor activity, and small-molecule therapeutic potential. ML models differentiated between patients with NMO and RRMS, with the performance of certain models exceeding 90% accuracy. RNA biomarkers driving model performance were associated with ribosomal dysfunction and viral infection. Regulatory networks of kinases and transcription factors identified biological associations and identified potential therapeutic targets. Small-molecule candidates capable of reversing perturbed gene expression were uncovered. Mitoxantrone and vorinostat-two identified small molecules with previously reported use in patients with NMO and experimental autoimmune encephalomyelitis-reinforced discovered expression signatures and highlighted the potential to identify new therapeutic candidates. Putative RNA biomarkers were identified that accurately distinguish NMO from RRMS and healthy individuals. The application of multivariate approaches in analysis of RNA-sequencing data further enhances the discovery of unique RNA biomarkers, accelerating the development of new methods for disease detection, monitoring, and therapeutics. Integrating biological understanding further enhances detection of disease-specific signatures and possible therapeutic targets.

Are monoclonals the only panacea for treatment of aquaporin-4 positive NMOSD? Experience from a low-&middle-income (LMIC) region.

OBJECTIVE: A plethora of monoclonals have ushered up for NMOSD treatment. However, their limited availability and cost concerns poses a challenge for usage in developing nations. We compared relapse rates and disabilities among aquaporin-4 positive(AQP4+ve) patients on conventional immunosuppressants and rituximab in a tertiary referral center in southern India. METHODS: This was a chart review of AQP4+ve patients registered under national demyelination registry maintained at institute. AQP4+ve patients were included if they were on azathioprine, MMF, methotrexate for six months; cyclophosphamide for three months and rituximab for one month. RESULTS: 207 records were screened, 154 fulfilled inclusion criteria. Drugs used were azathioprine (70), MMF (34) and rituximab (33). All three drugs were non-inferior to each other in terms of ARR reduction. Median EDSS at last follow-up was significantly lower for azathioprine(2;IQR:0-5) and rituximab(2;IQR:0.5-5) than MMF(3.5;IQR:2-5.6), however azathioprine was associated with highest switch rate(34.3%) and was the only drug which required change because of intolerance. Failure rate was least for rituximab(27.3%).Patients on azathioprine and MMF required higher mean duration of concurrent steroids(7.8±7.7 and 4.56±2.17 months respectively) when compared to rituximab(2.77±1.38) and had more relapses due to steroid withdrawal. CONCLUSION: Initial treatment with azathioprine, MMF and rituximab is comparable in terms of ARR reduction. Findings suggest that choice may be guided by adverse event profile of drug, rather than efficacy per se. Concurrent treatment duration with steroids should also guide clinical decision. Switch to second immunomodulation in event of initial failure adds to efficacy benefit, irrespective of the drug chosen.

Asymptomatic spinal lesions in patients with AQP4-IgG-positive NMOSD: A real-world cohort study.

OBJECTIVE: This study aims to explore the frequency and influencing factors of asymptomatic spinal lesions (ASLs) and their impact on subsequent relapses in patients with AQP4-IgG-positive NMOSD (AQP4-NMOSD) in a real-world setting. METHODS: We retrospectively reviewed clinical information and spinal MRI data from AQP4-NMOSD patients who had at least one spinal cord MRI during their follow-ups. Kaplan-Meier curves and Cox proportional hazards models were employed to ascertain potential predictors of remission ASLs and to investigate factors associated with subsequent relapses. RESULTS: In this study, we included 129 patients with AQP4-NMOSD and reviewed 173 spinal MRIs during attacks and 89 spinal MRIs during remission. Among these, 6 ASLs (3.5%) were identified during acute attacks, while 8 ASLs (9%) were found during remission. Remission ASLs were linked to the use of immunosuppressive agents, particularly conventional ones, whereas no patients using rituximab developed ASLs (p = 0.005). Kaplan-Meier curve analysis indicated that patients with ASLs had a significantly higher relapse risk (HR = 4.658, 95% CI: 1.519-14.285, p = 0.007) compared to those without. Additionally, the use of mycophenolate mofetil (HR = 0.027, 95% CI: 0.003-0.260, p = 0.002) and rituximab (HR = 0.035, 95% CI: 0.006-0.203, p < 0.001) significantly reduced the relapse risk. However, after accounting for other factors, the presence of ASLs did not exhibit a significant impact on subsequent relapses (HR = 2.297, 95% CI: 0.652-8.085, p = 0.195). INTERPRETATION: ASLs may be observed in patients with AQP4-NMOSD. The presence of ASLs may signify an underlying inflammatory activity due to insufficient immunotherapy. The administration of immunosuppressive agents plays a key role in the presence of remission ASLs and the likelihood of subsequent relapses.

Impact of neuromyelitis optica spectrum disorder on employment and income in the United States.

BACKGROUND AND OBJECTIVES: We aim to characterize the sociodemographic and clinical factors associated with loss of jobs, income, and work hours in people with neuromyelitis optica spectrum disorder (NMOSD) in the United States. METHODS: A REDCap-based survey was administered to working-age NMOSD patients (18-70 years old) querying demographic information, symptoms, immunosuppression, work hours, income, and caregiver work (11/2022-07/2023). Regression models were developed using MATLAB. RESULTS: Of 127 participants (97 female; 55% AQP4-antibody, 19% MOG antibody; 69% Caucasian, 7% Hispanic), with an average diagnosis age of 38.7 years, average disease duration of 6.4 years, mean 3.1 attacks, and 94% of whom were treated with immune system-directed therapy (53% rituximab, 8% satralizumab, 7% eculizumab, 6% mycophenolate mofetil, 4% inebilizumab, 2% azathioprine, 10% IVIg, 10% other), 56% lost a job due to NMOSD. Employment decreased 12% (80% pre- to 68% post-diagnosis). Thirty-six percent of participants said they no longer worked outside the home. Significant predictors for post-NMOSD diagnosis employment status included younger age, lower pain level, no walking aids, and having a job prediagnosis. Sixty-eight percent of those employed prediagnosis reduced their work hours, dropping an average of 18.4 h per month since being diagnosed (±10.1 h). Average annual income grew slowly at $1998 during the average 6.4 years of disease duration (14% of the value predicted by the U.S. Bureau of Labor Statistics). Sixty percent of participants had a regular unpaid caregiver; 34% of caregivers changed their work hours or job to help manage NMOSD. DISCUSSION: We provide a structured analysis of the impact of NMOSD on employment, work hours, and income in the United States, demonstrating its major effect on the livelihoods of patients and their caregivers.

The critical role of magnetic resonance imaging in the diagnosis of transverse myelitis: a case report.

INTRODUCTION: Transverse Myelitis is a rare inflammatory disorder of the spinal cord, characterized by the inflammation of the myelin sheath covering nerve fibers. Although rare, Transverse Myelitis holds significant clinical importance due to its potential life-altering consequences. The case report provides insight into the clinical presentation of Transverse Myelitis and the importance of Magnetic Resonance Imaging in confirming Transverse Myelitis. CASE PRESENTATION: A 27-year-old Nigerian female presented to a hospital facility after 2 months onset of paraplegia, urinary, and fecal incontinence. She was diagnosed with Acute Transverse Myelitis with Magnetic Resonance Imaging, a lacking imaging modality in Nigeria. On presentation, it was important to rule out spinal cord compression, a close differential to her presentation. Despite her late arrival at the facility, early diagnosis and prompt initiation of treatment with high-dose intravenous steroids and physiotherapy improved her quality of life. DISCUSSION: This case report reveals the poor health-seeking behavior in developing countries and the need for imaging modalities like Magnetic Resonance Imaging for improved diagnoses of rare neurological conditions such as Transverse Myelitis. The lack of healthcare infrastructure has led to clinical misdiagnosis, patient mismanagement, and underrepresentation of data in the country, underscoring the critical role of diagnostic tools for improved patient care pre-treatment and post-treatment. Additionally, follow-up of these patients is important to prevent the long-term sequelae of Transverse Myelitis like Neuromyelitis Optica or Multiple Sclerosis.

Systemic Connective Tissue Disease and Neuromyelitis Optica Spectrum Disorder Coexistence: A Systematic Review and Meta-Analysis.

BACKGROUND: Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions. METHODS: We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist. RESULTS: The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%-1.4%,) and 6.5% (95% CI: 4.7-8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5-54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%. CONCLUSIONS: Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities.

Efficacy and safety of rituximab in multiple sclerosis and neuromyelitis optica spectrum disorder.

In Thailand, resource limitations lead many multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients to use off-label immunosuppressants. This study assesses the efficacy and safety of rituximab (RTX) with a CD19-based reinfusion regimen among Thai MS and NMOSD patients. A retrospective review of patients at the Faculty of Medicine Siriraj Hospital from January 1994 to April 2023 was conducted. The primary outcome assessed was the change in annualized relapse rate (ARR) for patients using RTX for over a year. Secondary outcomes included changes in the Expanded Disability Status Scale (EDSS) scores, time to the first relapse after RTX initiation for patients using RTX for over a year, and an evaluation of the safety of RTX. The study encompassed 36 MS and 39 NMOSD patients. A majority of patients (91.7% of MS and 79.5% of NMOSD) experienced no relapses during a median follow-up of 30 months (Interquartile range [IQR] 20-46) and 31 months (IQR 23-41), respectively. The median ARR significantly decreased in both MS (from 0.77 [IQR 0.42-1.83] to 0 [IQR 0-0], p < 0.001) and NMOSD (from 0.92 [IQR 0.68-1.78] to 0 [IQR 0-0.17], p < 0.001) patients after switching to RTX, with no difference between those following a fixed 6-month time point regimen and a CD19-based reinfusion regimen. Median EDSS scores improved significantly at the last follow-up visit in both groups. The mean time to the first subsequent relapse was 8.3 ± 3.0 months in MS and 6.8 ± 1.7 months in NMOSD. Mild adverse drug reactions occurred in 44% of patients. RTX effectively prevents relapses in Thai MS and NMOSD patients, with no observed serious adverse drug reactions.

Clinical features and prognosis of Tibetan patients with neuromyelitis optica spectrum disorder are different from those of Han Chinese patients.

We compared the prognosis of Tibetan and Han Chinese patients with neuromyelitis optica spectrum disorder (NMOSD). The Expanded Disability Status Scale (EDSS) score at each attack, response to immunosuppressive therapy, risk of first relapse, severe attack, visual disability, motor disability, and total risk of disability were compared between Tibetan and Han Chinese patients. Tibetan patients showed higher EDSS during acute attacks. Annualized relapse rate did not differ between groups. Risk of severe attack, visual disability, and total risk of disability were higher in Tibetan patients. Tibetan patients with NMOSD have a higher risk of poor prognosis than Han Chinese patients.

Characteristics of recurrence risk perception and coping strategies in patients with neuromyelitis optica spectrum disorder: A qualitative study.

BACKGROUND: Although neuromyelitis optica spectrum disorder (NMOSD) has high recurrence and disability rates, cases of relapses can be recognized, and timely intervention can be provided if the risk of relapse is properly perceived. However, there have been no studies to explore patients' perceptions of recurrence risk and coping strategies. This study aimed to explore the characteristics of relapse risk perception and coping strategies of patients with NMOSD. METHODS: We adopted the phenomenological method of qualitative research. Face-to-face, semi-structured in-depth interviews were conducted with 15 patients with NMOSD. The interview data were then analyzed using the Colaizzi seven-step analysis. RESULTS: The analysis revealed five major themes. The first theme was the 'perception of possibility of relapse', which included subjectively underestimating the likelihood of relapse and shifted from underestimation to overestimation; the second theme was 'relapse warning signs perception'; the third theme was 'perception of relapse triggers', which included understanding relapse triggers, potential misconceptions about relapse triggers, and no identifiable cause of recurrence; the fourth theme was 'perception of the relapse consequences', encompassing severe impairment of body structure and function, prominent psychological problems, limited family roles and social functions, and heavy financial burden; and the final theme was 'relapse risk coping strategies', which included actively yearning for and seeking information support, recurrence risk prevention/management, limitations of coping strategies. CONCLUSIONS: This study's findings revealed that newly diagnosed patients as well as those who relapsed subjectively underestimated the likelihood of relapse before they had experienced multiple (two or more) relapses. In contrast, patients who had experienced multiple relapses had transitioned from initial underestimation to subsequent overestimation. Additionally, patients' compliance with medication was identified as a relapse-risk behaviors that was very manageable. The occurrence of relapse is associated with significant and extensive adverse effects on patients. Consequently, patients are eager to communicate with their healthcare providers regarding treatment planning and relapse management.

Eculizumab for a catastrophic relapse in NMOSD: case report.

Neuromyelitis optica spectrum disorders (NMOSD) are a group of inflammatory disorders of central nervous system characterized by immune-mediated demyelination and axonal damage, predominantly affecting spinal cord and optic nerves. This case report describes a 47-year-old woman with an aggressive form of seropositive NMOSD who had previously been treated with corticosteroids, plasma exchange, and cyclophosphamide. She experienced a life-threatening relapse that did not respond to conventional treatment, but ultimately showed a positive response to eculizumab. Furthermore, we describe the role of sNfL.

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.

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.