<h4>Objective</h4>This case series describes alternative treatments for adults with aquaporin 4 immunoglobulin G-seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) who exhibited disease activity despite having sustained B cell depletion for more than six months post-rituximab (RTX), a condition we defined as RTX resistance.<h4>Methods</h4>We conducted a single-center, retrospective case series of 10 AQP4-IgG-positive NMOSD patients who met our definition of RTX resistance and subsequently switched therapies. Here, AQP4 is linked to neuromyelitis optica.