Myasthenia gravis, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are antibody-mediated neuroimmune disorders that frequently affect women in their reproductive years and require careful treatment planning around pregnancy. Disease exacerbations (for myasthenia gravis) and attacks (for NMOSD and MOGAD) can occur during pregnancy, are common postpartum, and can cause preventable, long-term maternal disability. Many drug labels are conservative or recommend unnecessary prolonged washouts or avoidance of breastfeeding, creating uncertainty for physicians and patients. This Personal View integrates available evidence on conventional immunosuppressants and biological therapies, including complement inhibition, B-cell depletion, and neonatal Fc receptor blockade. Although data on pregnancy safety for newer treatments are few, preliminary data suggest that selected therapies could be continued during pregnancy to maintain disease stability and are compatible with breastfeeding. We offer expert recommendations for therapy choice, infant vaccinations, and fetal and infant monitoring in myasthenia gravis, NMOSD, and MOGAD.

BACKGROUND:Optical coherence tomography (OCT) enables in vivo assessment of retinal layers and is an emerging biomarker of neurodegeneration in multiple sclerosis (MS). In relapsing MS, peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness predict disease progression, but their role in primary progressive multiple sclerosis (PPMS) is unclear. OBJECTIVE:To determine whether pRNFL and GCIPL predict disability progression and retinal, brain, and spinal cord atrophy (SCA) in PPMS. METHODS:Retrospective longitudinal study of 69 PPMS patients with clinical, OCT, and magnetic resonance imaging (MRI) data. Patients stratified by pRNFL and GCIPL thickness tertiles (lower vs intermediate-upper). Annual thinning rates for pRNFL and GCIPL (aLpRNFL and aLGCIPL) estimated via linear regression. MRI assessed baseline and follow-up brain volumes, spinal cord area, and percentage of brain volume change (PBVC). Analyses included regression models, Kaplan-Meier, and Cox survival regression. RESULTS:pRNFL ⩽ 87 μm was associated with higher follow-up Expanded Disability Status Scale (EDSS) (6.0 (interquartile range (IQR) = 4.5-6.5) vs 4.0 (IQR = 3.0-6.0), p = 0.013). Risk of confirmed disability progression (CDP) increased 3.4-fold (95% confidence interval (CI) = 1.03-11.30, p = 0.044) over 2 years (IQR = 1.0-3.0), with median time to CDP of 1.84 vs 3.67 years (p = 0.027). Longitudinally, pRNFL ⩽87 μm showed faster retinal thinning (aLpRNFL = -1.66 vs -0.31 µm/year, p < 0.001), greater whole-brain atrophy (PBVC = -1.20%, p = 0.037), and greater SCA (B = 0.333, p = 0.008). CONCLUSION:In PPMS, pRNFL predicts disability progression and greater retinal, brain, and SCA, supporting its role as a surrogate marker of neurodegeneration in clinical trials.

Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are inflammatory disorders of the CNS with distinct immunopathologic mechanisms and treatment responses and partially overlapping clinical phenotypes. The identification of aquaporin-4 (AQP4)-IgG and MOG-IgG has transformed disease classification and diagnosis, enabled a classification of antibody-defined subgroups, and facilitated the development of targeted therapies. However, optimal use of these biomarkers in clinical practice requires careful interpretation within the appropriate clinical and radiologic context. This review synthesizes current evidence on established and emerging fluid biomarkers in NMOSD and MOGAD, with emphasis on analytical performance, biological relevance, and clinical utility. We review antibody detection using cell-based assays, highlighting differences between live and fixed platforms and the impact of antigen conformation on sensitivity and specificity, particularly for MOG-IgG. Common causes of false-positive and false-negative results are discussed, including low-titer reactivity, testing in low pretest probability populations, treatment-related antibody titer reduction, and assay-specific limitations. The diagnostic challenges posed by indiscriminate testing in adult cohorts with multiple sclerosis, in whom disease prevalence markedly exceeds that of MOGAD, are emphasized. We also discuss the role of repeat testing during acute attacks and paired serum-CSF analysis in improving diagnostic confidence when results are equivocal or discordant. Beyond disease-defining antibodies, we examine biomarkers of tissue injury and immune activation. Serum and CSF neurofilament light chain and glial fibrillary acidic protein provide complementary measures of neuroaxonal and astrocytic damage and show associations with attack severity, disease activity, relapse risk, and long-term disability. Cytokines, chemokines, and complement components reflect inflammatory pathways, including IL-6-driven immune activation in NMOSD and MOGAD and complement-mediated astrocytopathy in NMOSD, and may support mechanistic stratification and treatment monitoring in both conditions. We further review the contribution of CSF analysis, neuropathology, genetics, and antigen discovery platforms to refine disease classification, particularly in seronegative or atypical presentations. Finally, we outline priorities for future research, including assay harmonization, standardized sampling protocols, longitudinal biomarker profiling, and integrative multiomic approaches. Collectively, advances in biomarker science have the potential to improve diagnostic precision, guide individualized therapeutic strategies, and support de-escalation decisions in NMOSD and MOGAD.

Importance:Capturing individual multiple sclerosis (MS) progression is difficult; few studies have evaluated glial fibrillary acidic protein (GFAP) in large longitudinal cohorts with independent validation. Objective:To investigate whether serum GFAP levels and treatment-related changes are associated with future progression independent of relapse activity (PIRA). Design, Setting, and Participants:This was a prospective observational study using 2 large MS cohorts: the Swiss MS Cohort (SMSC; initiated in June 2012; data extraction September 22, 2025) and the Expression, Proteomics, Imaging, Clinical study (EPIC; initiated in July 2004; data extraction February 21, 2024). The study took place at tertiary MS centers (8 for SMSC and 1 for EPIC). A total of 2329 persons with MS from both cohorts with at least 1 available time point with neurofilament light chain (NfL) and GFAP measurements were included (overall 18 629 measurements). Exposures:Clinical data and NfL and GFAP z scores, collected and calculated every 6 or 12 months. Main Outcomes and Measures:Risk of future PIRA, defined as Expanded Disability Status Scale score worsening confirmed after 6 or more months without relapses (in SMSC), or a composite additionally including greater than 20% worsening in the 9-hole peg test or timed 25-ft walk test (in EPIC). Results:The SMSC and EPIC cohorts consisted of 1709 (13 375 samples; median [IQR] follow-up, 6.9 [2.5-10.7] years and age, 40.6 [32.1-50.1] years; 1128 [66.0%] female) and 620 (5254 samples; median [IQR] follow-up, 13.1 [9.4-14.0] years and age, 42.0 [35.0-50.0] years; 432 [69.7%] female) persons with MS, respectively. Consistent with prior work, high NfL was associated with relapse risk within the next year, whereas high GFAP was associated with long-term PIRA risk. In addition, elevated GFAP (z score >1.0 [84th percentile]) was associated with an average 40% higher hazard of short-term PIRA in the subsequent visit interval (SMSC: median [IQR] 346 [190-375] days; hazard ratio [HR], 1.45, 95% CI, 1.21-1.75; P < .001; EPIC: 385 [355-518] days; HR, 1.36; 95% CI, 1.07-1.71; P = .01). GFAP-based cohort enrichment in clinical trials targeting PIRA as an end point could reduce sample size by approximately 20%. Further, in SMSC, every yearly GFAP z score unit reduction during the first 2 years receiving fingolimod or B-cell-depleting therapy was associated with a lower risk of subsequent PIRA (54% risk reduction; HR, 0.46; 95% CI, 0.26-0.84; P = .01 and 67% risk reduction; HR, 0.33; 95% CI, 0.18-0.61; P < .001), respectively. Conclusions and Relevance:In this cohort study, elevated GFAP was associated with a higher risk of PIRA, while treatment-associated reductions were associated with a lower PIRA risk. Together, these results suggest that serum GFAP may serve as a biomarker for personalized risk stratification and treatment monitoring and as a screening tool to reduce cohort size in clinical trials targeting MS progression.

OBJECTIVE:The objective of this study was to investigate the ability of patient-reported/administered outcomes to capture disability worsening and progression independent of relapse activity (PIRA) in multiple sclerosis (MS). METHODS:We included patients from the longitudinal multicenter MS PATHS cohort with ≥3 assessments and >6 months follow-up. PIRA was defined on the patient-determined disease steps (PDDS) and self-administered tests assessing walking speed, manual dexterity, and processing speed, in the absence of self-reported relapses. We assessed (i) prevalence of PDDS/self-administered test-based disability worsening and PIRA definitions; (ii) their concurrent validity, through the association with worsening and PIRA definitions based on the expanded disability status scale (EDSS; Barcelona subcohort); and (iii) their clinical meaningfulness, through the correlation with brain magnetic resonance imaging (MRI) and quality-of-life (QoL) data trajectories. RESULTS:We included 9,088 patients (73% female patients; age = 46.8 years; disease duration = 14.2 years). Over a 3-year follow-up, 4,066 (45%) patients worsened on ≥1 patient-reported/administered outcome, of which 2,357 (58%) developed PIRA. In the Barcelona subcohort (N = 279), 68 (24%) patients developed EDSS-based worsening, of which 30 (44%) developed EDSS-based PIRA; 99 of 279 (35%) worsened on ≥1 patient-reported/administered test, of which 78 of 99 (79%) had PIRA. Worsening (but not PIRA) on PDDS was associated with EDSS-based worsening (odds ratio = 3.03 [1.42; 6.43], p = 0.004). PDDS/self-administered-test-based worsening or PIRA strongly correlated with accelerated brain atrophy and T2 lesion volume increase compared to non-worseners (p < 0.05), and showed worse QoL (p < 0.05). INTERPRETATION:Despite only partial agreement with EDSS-based definitions, PDDS/self-administered test-based worsening and PIRA definitions were clinically meaningful, by identifying patients with greater brain damage and poorer QoL, supporting their use in clinical practice. ANN NEUROL 2026;100:525-546.

OBJECTIVE:This article describes the features and application of the 2024 McDonald criteria for the diagnosis of multiple sclerosis (MS). LATEST DEVELOPMENTS:The updated 2024 McDonald criteria are designed to be inclusive, with multiple new pathways to diagnosis that are applicable across the age spectrum and for patients with typical, nonspecific, or incidental presentations. New fluid and MRI biomarkers have been incorporated, including the kappa free light chain index, the central vein sign, and paramagnetic rim lesions. Anatomic regions for the fulfillment of dissemination in space now include the optic nerve as a fifth location, incorporating evidence of an optic nerve lesion demonstrated by either MRI, optical coherence tomography, or visual evoked potentials. ESSENTIAL POINTS:The 2024 McDonald criteria strongly recommend the confirmation of objective evidence of central nervous system involvement by imaging in addition to clinical findings, while additional biomarkers may be needed in specific instances. However, if these paraclinical tools are unavailable, a pragmatic approach incorporating clinical findings is permitted. MS diagnosis requires careful neurologic evaluation and expertise for the interpretation of paraclinical findings; the accurate performance of the diagnostic criteria still relies on the clinician's knowledge of typical clinical presentations and MRI findings of MS and the recognition of red flags suggesting alternative diagnoses. The revised criteria can be applied at all ages and for asymptomatic individuals; however, caution is required to avoid misdiagnosis, particularly for pediatric, older-onset, and asymptomatic presentations.

BACKGROUND:Accelerated biological ageing has been proposed as a key mechanism influencing disease progression in multiple sclerosis. Anti-Müllerian hormone (AMH), a marker of ovarian reserve, may reflect biological ageing in women and could be associated with disability progression. We aim to evaluate the prognostic implications of AMH levels measured at the first demyelinating event (FDE) suggestive of multiple sclerosis (MS). METHODS:This retrospective study analysed prospectively collected data from three Spanish neuroimmunology centres (since 1994). It included 365 females aged 20-45 years with serum AMH measured within 2 years of onset. According to AMH tertiles (n, median ng/mL (range)), participants were classified as follows: high (n=121; 4.6 (3.2-17.4)), medium (n=122; 2.1 (1.3-3.2)) and low (n=121; 0.6 (0.01-1.3)). A total of 145 healthy females served as controls. Age-adjusted multivariable linear regression models assessed associations between AMH and baseline clinical, radiological and serum biomarkers. Cox regression models evaluated the risk of Expanded Disability Status Scale 3.0, second relapse, progression independent of relapse activity and relapse-associated worsening. RESULTS:At FDE, median (range) age was 32.9 (22.2-44.9) years, follow-up 6.5 years (0.01-29.4) and AMH 2.2 (0.01-17.4); 68% received disease-modifying treatment. AMH levels did not differ between patients and controls and were inversely correlated with chronological age (β -1.21 (95% CI -1.42 to -1.00), p<0.001). After adjustment for chronological age, AMH showed no independent association with clinical, radiological or biomarker measures, or long-term outcomes. CONCLUSIONS:AMH levels at the time of an FDE suggestive of MS were not associated with baseline activity or long-term outcomes related to relapses or disability. Our findings suggest that the apparent associations between AMH and disease characteristics are largely driven by chronological age, supporting the concept that ovarian reserve primarily reflects biological ageing rather than an independent determinant of MS progression.

Background:The 2024-revised McDonald criteria may enable earlier diagnosis of multiple sclerosis (MS) through inclusion of optic nerve involvement as fifth neuroanatomical topography, novel MRI biomarkers, cerebrospinal fluid (CSF) kappa free light chains (KFLC), and classification of radiologically isolated syndrome (RIS) as MS. Their applicability in routine practice remained for evaluation. Methods:In this prospective single-centre cohort study in Germany, adults presenting between October 1, 2020, and June 30, 2025, with a first demyelinating event or RIS were screened. Participants underwent conventional diagnostic work-up according to the 2017-revised McDonald criteria, including contrast-enhanced MRI, visual evoked potentials (VEP), and CSF analysis. Novel MRI markers and optical coherence tomography were not systematically available. Primary outcome was the proportion of individuals fulfilling the 2024-revised versus the 2017-revised McDonald criteria at baseline assessment. Findings:Applying the 2024-revised criteria, 201/215 individuals (93.5%) fulfilled diagnostic criteria for MS versus 181/215 (84%) using the 2017 revision (p < 0.0001). Additional diagnoses resulted from optic nerve involvement (55%) and RIS reclassification (35%). VEP identified optic nerve lesions in 89% of cases. Overall, 102/201 (51%) individuals fulfilled diagnostic criteria based on MRI findings alone, whereas 99/201 (49%) additionally required inflammatory CSF findings and dissemination in time. Interpretation:Application of selected components of the 2024-revised McDonald criteria increased the proportion of individuals fulfilling the diagnostic criteria, mainly through inclusion of optic nerve involvement and recognition of RIS. CSF analysis remained important for diagnosis and differential diagnostics. Further studies should evaluate the contribution of novel imaging biomarkers. Funding:No external funding was received.

OBJECTIVE:To determine the prevalence and clinical characteristics of patients with "low-positive" (LP) MOG-IgG (titres 1:160-1:320) among adults with a first demyelinating event (FDE) suggestive of multiple sclerosis (MS). METHODS:From the Barcelona CIS inception cohort, we included adult patients with serum collected ≤ 6 months from the FDE. MOG-IgG was assessed by a cell-based assay with flow cytometry (CBA-FC). Demographic, clinical, and paraclinical data were compared among seronegative, LP, and "clear-positive" (CP; ≥ 1:640) patients. Supporting MOGAD features and final diagnoses were retrospectively reviewed in seropositive cases. RESULTS:Of 613 patients, 42 (6.9%) were MOG-IgG positive (CP = 17; LP = 25). LP patients were indistinguishable from seronegative patients but differed from CP patients, who more frequently had optic neuritis, lacked cerebrospinal fluid-oligoclonal bands, and were less likely to meet the McDonald criteria (p < 0.05). At the last follow-up, 64% of LP versus 18% of CP patients were diagnosed with MS (p = 0.004). Only one LP patient fulfilled MOGAD criteria, compared with 14 CP patients (p < 0.001). INTERPRETATION:Lowering the CBA-FC positivity threshold to ≥ 1:160 had limited diagnostic yield in this MS-predominant cohort, as most LP cases were ultimately diagnosed with MS. These findings support cautious interpretation of LP MOG-IgG results in this clinical setting.

Importance:Live attenuated measles-mumps-rubella (MMR) and varicella vaccines are recommended for immunocompetent people with multiple sclerosis (MS) lacking immunity. However, concerns about postvaccination relapses may contribute to vaccine hesitancy, and robust data addressing this risk remain limited. Objective:To assess whether the risk of MS relapse within 1 year after MMR or varicella vaccination is not unacceptably worse than risk after no such vaccination based on a predefined noninferiority margin. Design, Setting, and Participants:This cohort study used prospectively collected data from July 2016 to October 2024 for people with MS at a tertiary MS center in Barcelona, Spain, who received at least 1 dose of live attenuated MMR and/or varicella vaccine due to serologic susceptibility. Vaccinated patients were matched 1:2 with unvaccinated control individuals with MS by sex, age, and epoch of first demyelinating event. Exposures:Live attenuated MMR and/or varicella vaccine. Main Outcomes and Measures:Primary outcomes were relapse count and time to first relapse within 1 year of time 0, analyzed using Poisson and Cox proportional hazards regression models with inverse probability weighting based on a propensity score including treatment category, Expanded Disability Status Scale score, and annualized relapse rate in the prior year. Noninferiority was predefined as an annualized relapse rate ratio with an upper bound of the 95% CI less than 1.4. Results:A total of 369 people with MS were included, of whom 123 were vaccinated (mean [SD] age, 28.75 [8.72] years; 85 females [69.1%]) and matched to 246 unvaccinated controls (mean [SD] age, 28.66 [8.60] years; 170 females [69.1%]). Overall, 36 relapse events were observed (15 [41.7%] among vaccinated patients and 21 [58.3%] among unvaccinated controls). In the weighted Poisson model, although relapse incidence was not significantly different between vaccinated and unvaccinated individuals (incidence rate ratio, 0.52; 95% CI, 0.23-1.06), the noninferiority criterion was met. Similarly, weighted Cox proportional hazards regression models showed no difference in hazard of relapse between groups (hazard ratio [HR], 0.55; 95% CI, 0.25-1.17) but the noninferiority criterion was met. Sensitivity and exploratory analyses, including time-dependent adjustment for postbaseline treatment exposure (HR, 0.60; 95% CI, 0.27-1.33), restriction to the high-risk period (n = 15 events), and comparisons of magnetic resonance imaging before (n = 43 events) and after (n = 21 events) exposure in vaccinated patients, revealed findings consistent with those of the primary analysis. Conclusions and Relevance:In this cohort study of nonimmunosuppressed people with MS, vaccination with live attenuated MMR or varicella vaccine was not associated with increased risk of postvaccination relapse. The results support the administration of these vaccines when indicated and may help reassure clinicians and patients, reducing vaccine hesitancy.

Multiple sclerosis (MS) is a potentially disabling disease that shows marked variability in its severity and underlying mechanisms. Early prediction of patients at risk of specific unfavourable outcomes may be key to treatment stratification and management. Here, we propose a prognostic framework, called the Spider-MS model, to predict a wide range of relevant outcomes at the individual level, at symptom onset. We included patients from the Barcelona first-attack cohort, i.e. with a first demyelinating attack suggestive of multiple sclerosis, younger than 50 years old at symptom onset and seen in the clinic within 3 months of the first attack, to build the Spider-MS model (original cohort). Patients with a first demyelinating attack from the Royal Melbourne Hospital were used to validate the model externally (validation cohort). All patients were prospectively assessed clinically, with the Expanded Disability Status Scale (EDSS) and relapse tracking, and through brain and, in some cases, spinal cord MRI. Spider-MS was built as a set of eight accelerated failure models with Weibull distribution, one for each outcome, including McDonald 2017 diagnosis, second attack, yearly rate of new T2 lesions > 2, relapse-associated worsening (RAW) at the first attack and at subsequent attacks, confirmed and sustained disability worsening, progression independent of relapse activity (PIRA) and EDSS 3.0. Model predictors included age, sex, first attack topography, brain and spinal cord lesions, CSF oligoclonal bands and percentage of time on high-/moderate-efficacy treatment before the outcome. We included 1180 patients from Barcelona (mean age 32.37 years, 810 females) and 108 from Melbourne (32.41 years, 78 females). Median follow-up times were 10.80 and 11.10 years, respectively. In the original cohort, 797/1180 (67.5%) fulfilled the McDonald criteria, 121/1180 (10.3%) developed RAW at subsequent relapses and 290/1180 (24.6%) developed PIRA over the follow-up period. The prediction models reached moderate-high accuracy levels (Harrell's C values: 0.653-0.823) and showed that older age, cord involvement at first attack, greater number of brain and cord lesions, presence of CSF oligoclonal bands and lower percentage of time on treatment predicted a greater risk of unfavourable outcomes, with varying effects depending on the outcome. When the Spider-MS model was applied to the external cohort, for all outcomes except for RAW at first or subsequent attacks, the prediction models reached moderate-high accuracy values (Harrell's C = 0.623-0.766). In general, patients with the highest predicted risks experienced acute inflammatory activity or disability earlier than lower-risk patients. In conclusion, our Spider-MS model can be considered a promising individual predictive tool with the potential to inform clinical practice.

BACKGROUND AND OBJECTIVES:Serum neurofilament light chain (sNfL) reflects inflammatory axonal damage in relapsing multiple sclerosis (RMS). Longitudinal sNfL dynamics may aid treatment response assessment, although data on expected changes under disease-modifying treatments remain limited, particularly in real-world practice. This study evaluated whether on-treatment changes in sNfL were associated with subsequent evidence of disease activity (EDA) and whether they provided complementary information to established treatment response scoring systems (TRSS). METHODS:This prospective, real-world cohort study was conducted at the Multiple Sclerosis Center of Catalonia (Cemcat). Adult RMS patients initiating disease-modifying treatments (DMTs) with serum samples at treatment initiation (baseline) and after 1 year (Y1) were included. The primary exposure was change in sNfL z-scores (ΔzNfL = zNfLY1 - zNfL-baseline) analyzed using data-derived thresholds (ΔzNfL ≥0 and <0.5-point reduction). At Y1, Expanded Disability Status Scale progression, clinical/radiologic activity, and TRSS (Rio [RS], modified Rio [mRS], and MAGNIMS) were assessed. The primary outcome was EDA between years 1 and 2 (EDA-Y2). Multivariable logistic regression models evaluated associations between ΔzNfL and EDA-Y2, as well as the added value of ΔzNfL across TRSS strata. RESULTS:A total of 329 patients (66.3% female; median age 39 years) initiated 352 DMTs; 342 remained on treatment for ≥1 year and 182 had complete EDA-Y2 data. Mean (SD) ΔzNfL at Y1 was -0.62 (1.2), with greater reductions in monoclonal antibody-treated and treatment-naïve patients. Lack of zNfL reduction over the first year (ΔzNfL ≥0) was associated with higher odds of EDA-Y2 in the overall cohort (OR [95% CI], p: 3.07 [1.47-6.39], 0.003), in treatment-naïve cases (14.04 [2.47-79.93], 0.003), and in those achieving No Evidence of Disease Activity (NEDA-3) at Y1 (4.54 [1.26-16.30], 0.02). Similar associations were observed for <0.5-point reductions. Adding ΔzNfL to TRSS showed persistent associations with EDA-Y2 despite otherwise favorable scores [e.g., RS: 2.26 (1.12-4.59), 0.024]. DISCUSSION:Failure to reduce zNfL levels after 1 year of treatment was associated with subsequent disease activity, even in patients otherwise considered stable, providing complementary information to clinical and MRI-based monitoring. Limitations include incomplete follow-up and the modest discriminative performance of ΔzNfL, supporting a complementary rather than stand-alone role for zNfL dynamics.

Importance:Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) lacks proven relapse-preventive therapies. While clinical trials are ongoing, safety data may be limited and approved drugs are costly. Studies of interleukin 6 receptor blocker (IL-6RB) in MOGAD are limited by small numbers and no comparative studies, contributing to low use. Objective:To evaluate the impact of IL-6RB therapy on relapse rates in MOGAD and compare relapse frequency with intravenous immunoglobulin (IVIG). Design, Setting, and Participants:This international, multicenter, retrospective cohort study (January 1, 2015, through December 31, 2025) included a historical IVIG-treated cohort of varying doses. The study took place across sites in North and South America (US, Canada, Mexico, Argentina, Brazil, Chile, Colombia, and Peru). Patients with MOGAD (n = 116, no excluded patients) who received at least 1 dose of an IL-6RB were included. These data were analyzed in January 2026. Exposures:Tocilizumab or satralizumab. Main Outcomes and Measures:Annualized relapse rate (ARR) during IL-6RB therapy, time to next relapse after treatment initiation, and adverse events. Outcomes were compared with the IVIG cohort using inverse probability of treatment weighting (IPTW) adjusted for age, sex, prior ARR, and concomitant therapies. Results:A total of 116 patients with MOGAD (89% relapsing) receiving IL-6RB (tocilizumab, 104 [90%] and satralizumab, 12 [10%]) were included; overall, 60.3% were female, 39.7% were male, and 18% were younger than 18 years. The median (IQR) IL-6RB treatment follow-up was 1.4 (0.7-2.5) years and 23 relapses occurred during 241.8 person-years of IL-6RB therapy. The ARR decreased from 0.64 (95% CI, 0.58-0.70) for relapsing MOGAD before IL-6RB to 0.09 (95% CI, 0.06-0.14) during IL-6RB treatment (incidence rate ratio, 0.08; 95% CI, 0.04-0.16). Adverse events occurred in 58 patients (50%), most commonly mild infections, although 10 (9%) had severe infections. In the IVIG cohort (n = 59), 30 relapses occurred over 133.8 person-years (ARR, 0.22; 95% CI, 0.15-0.32). After IPTW, IL-6RB was associated with a lower hazard ratio (HR) than the group who underwent IVIG therapy less than 1 g/kg every 4 weeks (HR, 4.5; 95% CI, 2.0-9.8), with no significant difference vs the group who underwent IVIG 1 g/kg or more every 4 weeks (HR, 2.0; 95% CI, 0.8-4.5). Conclusions and Relevance:In this multicenter observational cohort, IL-6RB use in MOGAD was associated with low relapse rates and a favorable safety profile, though severe infections occurred occasionally. Relapse rates were lower than the group who underwent IVIG less than 1 g/kg every 4 weeks but not significantly different from the group who underwent IVIG 1 g/kg or more every 4 weeks. This supports IL-6RB as a potential relapse-prevention therapy in MOGAD; the wide availability and relative affordability of tocilizumab may enable broad global use.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare antibody-mediated neuro-autoimmune disease. Monoclonal antibodies targeting B cell antigens CD19 and CD20, the interleukin-6 receptor, or the complement cascade are used as preventive therapies to reduce relapse rates. We conducted a network meta-analysis (NMA) to compare the effect of rituximab on time to first relapse with ravulizumab, eculizumab, inebilizumab, and satralizumab in patients with NMOSD who are aquaporin-4 (AQP4)-IgG-positive. A systematic search was conducted in PubMed, Scopus, CINAHL, EMBASE, Web of Science, the Cochrane Library, and gray literature sources up to October 31, 2024, and updated on November 1, 2025, following PRISMA guidelines. A network meta-analysis of randomized and open-label trials was conducted to compare time to first relapse between rituximab and other monoclonal antibody therapies. From 6337 records, 3825 duplicates were removed; 2512 were screened, 2327 excluded, leaving eight trials. The prior treatment, relapse history, and definitions and adjudication of relapse varied across studies. Rituximab showed higher hazard ratio (HR) point estimates for time to first relapse compared with ravulizumab with or without immunosuppressive therapies (IST) (HR 5.00, 95