Satralizumab 120mg/1ml solution for injection pre-filled syringes

Background and objectivesMonoclonal antibodies have transformed the treatment of neuromyelitis optica spectrum disorder (NMOSD), yet their comparative efficacy by aquaporin-4 immunoglobulin G (AQP4-IgG) serostatus remains uncertain. We conducted a systematic review and meta-analysis to compare monoclonal antibody efficacy between AQP4-IgG seropositive and seronegative NMOSD patients.MethodsWe searched PubMed/MEDLINE, Embase, and Cochrane CENTRAL from inception through January 2025 for studies comparing monoclonal antibody efficacy outcomes (rituximab, eculizumab, satralizumab, inebilizumab, tocilizumab, or ravulizumab) between seropositive and seronegative NMOSD patients. Primary outcomes included annualized relapse rate (ARR) and relapse events. Secondary outcomes included disability progression (Expanded Disability Status Scale [EDSS]) and infectious adverse events. Random-effects meta-analysis was performed. The protocol was registered in PROSPERO (CRD1049290).ResultsThirteen studies (4 randomized controlled trials [RCTs], 9 observational) comprising 1284 patients (1010 seropositive; 274 seronegative) were included. Seropositive patients had significantly lower relapse risk (risk ratio [RR] = 0.66; 95% CI: 0.49-0.89; p = 0.007; I2 = 0%; 9 studies), indicating 34% greater efficacy in preventing relapses. An RCT-only subgroup analysis demonstrated a 59% relative risk reduction favoring seropositive patients (RR = 0.41; 95% CI: 0.25-0.69; p = 0.0008; I2 = 0%). No significant differences were observed for continuous ARR (standardized mean difference [SMD] = 0.23; p = 0.61; I2 = 94%), disability progression (SMD = 1.07; p = 0.32; I2 = 96%), or infectious adverse events (RR = 1.13; p = 0.61; I2 = 0%).DiscussionMonoclonal antibodies demonstrate significantly greater efficacy in preventing relapses in AQP4-IgG seropositive compared with seronegative NMOSD patients. Serostatus should inform treatment selection and expectations. Comparable safety profiles support continued use in seronegative patients, though further research is needed to optimize therapeutic strategies for this population.

Abstract licence: CC BY

Autoimmune inflammatory diseases of the central nervous system (CNS), including autoimmune encephalitis (AE), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), have emerged over the last two decades as distinct nosological entities with specific autoantibody targets, clinical phenotypes, and treatment responses. Recognition of their autoimmune basis has transformed management from largely supportive and empiric approaches toward mechanism-based immunotherapy. However, these conditions remain rare, clinically heterogeneous, and frequently severe, posing substantial challenges for the design and conduct of robust clinical trials. This review synthesizes current evidence on advances in clinical research and immunotherapy across the major autoimmune CNS disease groups, with a particular focus on trial designs, endpoints, and the evolution from observational cohorts to randomized controlled trials. In AE, first-line immunotherapies (high-dose glucocorticoids, intravenous immunoglobulin, and plasma exchange) remain based mainly on observational data, while second-line therapies such as rituximab and cyclophosphamide are increasingly used despite limited comparative trial data. Recent systematic reviews and individual patient data meta-analyses have highlighted both the potential and the limitations of existing observational evidence, and several randomized phase II-III trials are now underway evaluating agents including bortezomib, satralizumab, and inebilizumab. In NMOSD, the therapeutic landscape has advanced more rapidly, with multiple pivotal randomized controlled trials of targeted biologics (e.g. complement inhibition with eculizumab, B-cell depletion with inebilizumab, interleukin-6 [IL-6] receptor blockade with satralizumab) demonstrating large reductions in relapse risk and leading to regulatory approvals. For MOGAD, most data still derive from retrospective cohorts and extrapolation from NMOSD and multiple sclerosis, but several disease-specific trials are ongoing that investigate IL-6 receptor inhibitors, neonatal Fc receptor (FcRn) antagonists, and purine synthesis inhibitors. Across these disorders, key challenges for clinical research include small and geographically dispersed patient populations, variable access to diagnostic antibody testing, limited validation of outcome measures that capture cognitive and psychiatric morbidity, and underrepresentation of pediatric, elderly, and low-resource populations. Emerging strategies include use of adaptive and basket trial designs, registry-based and pragmatic trials, and increased reliance on international collaborative networks. Addressing these methodological and equity-related issues will be essential to translate immunopathological insights into broadly accessible, evidence-based care for patients with autoimmune CNS disease.

Abstract licence: CC BY-NC-SA

BackgroundThere are numerous immunotherapies that are effective in preventing relapses in neuromyelitis optica spectrum disorder (NMO-SD). With head-to-head clinical trials between immunotherapies lacking, Bayesian network meta-analysis can be used to compare treatment interventions. Previous network meta-analyses have compared monoclonal antibodies but either not included newer complement inhibitors or earlier immunotherapies such as rituximab or tocilizumab.ObjectiveTo compare immunosuppressive treatments used in relapse prevention in NMO-SD.MethodsPubMed, EMBASE and Scopus were searched for randomised controlled trials until 20th September, 2024. Search terms strategy included neuromyelitis optica, antibody and relapse. Randomised controlled trials testing immunotherapies used in relapse reduction in NMO-SD were included. Of 550 studies screened, 8 clinical trials initially met inclusion criteria. The study was performed according to PRISMA guidelines by multiple observers. Bayesian fixed-effect network meta-analysis was conducted. The primary outcome was time to relapse. The secondary outcome was annualised relapse rate. Sensitivity analysis was undertaken in seropositive patients. Treatments were ranked using a probability measure called surface under the cumulative rank curve (SUCRA).ResultsEight studies were included that contained a total 851 patients [716 (84%) seropositive]. There were six treatment interventions-ravulizumab, eculizumab, tocilizumab, rituximab, inebilizumab, satralizumab and the control arm (placebo/azathioprine). Ravulizumab was the ideal treatment (HR 0.00 (95%CrI 0.00-0.03), SUCRA 0.99) with a 98% probability of being the superior treatment in increasing time to relapse in NMO-SD. This was supported by secondary analysis of annualised relapse rate and the sensitivity analysis in seropositive patients.DiscussionThese findings suggest that ravulizumab had the highest probability of being the most superior treatment in decreasing relapse risk in NMO-SD.

Abstract licence: CC BY