Rituximab Versus Ravulizumab, Inebilizumab, Satralizumab, and Eculizumab in NMOSD

Summary

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare autoimmune condition that mainly affects the eyes and spinal cord, causing serious symptoms such as vision loss, paralysis, and severe pain. This trial compares the effectiveness and safety of five medications commonly used to prevent NMOSD relapses: rituximab, ravulizumab, inebilizumab, satralizumab, and eculizumab. In this study, 160 adults with NMOSD who test positive for a specific antibody (AQP4-IgG) will participate. They will be randomly assigned to receive either rituximab or one of the four other FDA-approved medications. The main goal is to find out which treatment best prevents relapses and has fewer serious side effects. The trial will also measure disability, patient satisfaction, quality of life, and biomarkers that help track disease activity. Participants will have regular assessments, including medical exams, surveys, and tests for vision, walking ability, and brain function. They will report any side effects or health issues experienced during the study. The trial will last from one to four years for each participant. This research aims to help patients and doctors make better-informed treatment decisions by providing clear evidence about the best available therapies for NMOSD.

Detailed Description

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune inflammatory disorder primarily affecting the optic nerves and spinal cord, leading to symptoms such as blindness, severe muscle weakness, paralysis, and significant pain. This study aims to directly compare the clinical effectiveness and safety profiles of five distinct therapies widely utilized to prevent disease relapses in patients with NMOSD who test positive for aquaporin-4 antibodies (AQP4-IgG): rituximab, ravulizumab, inebilizumab, satralizumab, and eculizumab. The study is designed as an international, multicenter, randomized, adaptive clinical trial. It involves enrolling 160 adult participants diagnosed with AQP4-IgG positive NMOSD, who will be randomized in equal numbers to receive either rituximab or one of the four other FDA-approved therapies-ravulizumab, inebilizumab, satralizumab, or eculizumab. Patients randomized to the non-rituximab group will undergo further randomization into one of these four comparator medications. Additionally, the study incorporates an observational cohort for patients who decline randomization but agree to be followed according to the same protocol. The primary objective is to evaluate the comparative effectiveness of rituximab versus the other treatments in preventing NMOSD relapses and treatment failure due to adverse events. Secondary objectives include comparing disability outcomes, evaluating treatment-related adverse events, and assessing impacts on patient-reported quality of life, as well as examining changes in biomarkers relevant to NMOSD disease activity. Participants will undergo comprehensive evaluations at regular intervals, including detailed neurological examinations, standardized functional assessments (Expanded Disability Status Scale \[EDSS\], Multiple Sclerosis Functional Composite \[MSFC\]), visual acuity and contrast sensitivity testing, and cognitive assessments. Additionally, patient-reported outcomes such as fatigue, pain, mental health status, and overall quality of life will be collected systematically through validated surveys. Safety assessments will include regular monitoring of blood work, clinical evaluations for infections and other complications, and documentation of all adverse events. Advanced exploratory analyses will also include biomarker studies involving optical coherence tomography (OCT) to assess retinal nerve fiber layer loss, and assays for serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels. The study will track direct and indirect healthcare costs, as well as impacts on employment and caregiver burden. The duration of participation will range from one to four years, depending on when participants enroll and their clinical outcomes. All data will be rigorously analyzed using advanced statistical methods, including time-to-event analyses, mixed-effects models, and Bayesian hierarchical approaches to allow robust comparative effectiveness evaluations. Ultimately, this research aims to provide high-quality, head-to-head data to inform clinical decision-making, optimize treatment strategies, and improve patient outcomes for those living with NMOSD.

Eligibility Criteria

Interventions