BEST-NMOSD

Treatment tested

• Rituximab

  B-lymphocyte antigen CD20 binding agent

• Eculizumab

  Complement C5 inhibitor

• Ravulizumab

  Complement C5 inhibitor

• Satralizumab

  IL6Ralpha/GP130 antagonist

• Inebilizumab

  B-lymphocyte antigen CD19 binding agent

Other measures (12)

Inclusion Criteria: * Diagnosis of NMOSD according to the 2015 International Panel for NMO Diagnosis (IPND) consensus criteria. * Seropositivity for AQP4 immunoglobulin G (AQP4-IgG) confirmed by a cell-based assay (either live or fixed) that meets the threshold for positivity set by the local testing laboratory. * Age ≥18 years at the time of consent. * Ability and willingness to provide informed consent and comply with all study procedures, including scheduled visits, laboratory tests, and assessments. * Eligible to receive any of the study drugs based on clinical judgment Exclusion Criteria: * Known active hepatitis B virus (HBV) infection, defined as a positive hepatitis B surface antigen or detectable HBV DNA by PCR. * Known active hepatitis C virus (HCV) infection, defined as detectable HCV RNA by PCR. * Known active or latent tuberculosis, evidenced by a positive interferon-gamma release assay (IGRA) unless fully treated per local guidelines before enrollment. * Known or suspected immunodeficiency disorders, including but not limited to HIV infection with CD4 count \<200 cells/mm³ or any condition requiring chronic immunosuppressive therapy outside the scope of the study drugs. * Pregnancy or breastfeeding, or intention to conceive during the study period. Pregnancy is excluded due to insufficient safety data for the investigational treatments in this population. Women of childbearing potential must agree to use effective contraception throughout the study and for a defined period following the last dose of study drug, per product labeling or institutional guidance. * Any medical, psychiatric, or neurological condition that, in the investigator's opinion, may interfere with study participation, pose additional risk to the participant, or confound interpretation of study results. * Inability or unwillingness to comply with the requirements of the protocol, including scheduled visits, evaluations, or procedures, based on investigator assessment. * Known hypersensitivity or severe allergic reaction to any component of the study drugs or pre-medications required for infusion.

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.