De-Escalating and Discontinuing Immunotherapies in Patients With NMOSD and MOGAD

Abstract

Antibody-mediated inflammatory diseases of the CNS, including aquaporin-4 antibody neuromyelitis optica spectrum disorder (AQP4-Ab NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD), have undergone major therapeutic transformation with the advent of sensitive antibody assays and targeted immunotherapies. These advances have markedly reduced relapse rates and improved long-term outcomes. With improved disease control, questions regarding optimal treatment duration and the possibility of de-escalation or discontinuation are increasingly relevant. In AQP4-Ab NMOSD, relapses are typically severe and disabling, and most observational studies show a high risk of reactivation after tapering or withdrawal. Thus, discontinuation is never recommended. Successful de-escalation has been reported in selected patients with prolonged remission, although relapse risk persists, underscoring the need for individualized decisions and close monitoring. In contrast, MOGAD is clinically heterogeneous. Many patients, particularly children, experience a monophasic illness with good recovery, whereas relapse risk in adults appears to decline after several years. De-escalation strategies can thus be applied for anti-CD20 and IVIG. Recent cohort studies suggest that even discontinuation may be feasible after 2 to 5 years of remission in children and adults, especially in those who become seronegative for myelin oligodendrocyte glycoprotein immunoglobulin G. In seronegative NMOSD, the evidence base is limited and prognosis uncertain; attacks can be severe, no therapies are specifically approved, and although some experts suggest that discontinuation may be considered after 5 years of stability, this remains guided by expert opinion alone. Treatment de-escalation is sometimes necessary because of adverse effects, comorbidities, infections, treatment fatigue, or life circumstances such as pregnancy. In pregnancy, management requires balancing maternal disease control with fetal safety, with strategies ranging from continuation of selected therapies to temporary tapering or deferral. Monitoring with MRI, OCT, and emerging fluid biomarkers offers potential to detect early recurrence of disease activity, although none are validated for routine use. Prospective studies, real-world registry data, and dedicated trials are urgently needed to inform safe and patient-centered de-escalation/discontinuation strategies.