Therapeutic updates in NMOSD and MOGAD: From present practice to future promise

Aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are rare, antibody-mediated inflammatory disorders of the central nervous system (CNS). Although historically grouped under the umbrella of multiple sclerosis, both entities differ markedly in pathophysiology, clinical course, prognosis and therapeutic requirements. The identification of disease-specific autoantibodies has not only refined diagnostic accuracy but has also highlighted fundamental differences in therapeutic strategy, particularly regarding the need for and choice of long-term immunosuppression. While acute management of both conditions relies on similar approaches, the long-term treatment paradigms diverge. Sustained immunosuppression may not be required for all patients with MOGAD, whereas AQP4+NMOSD typically demands continuous therapy, in which agents directed against complement activation, IL-6 signaling, and B-cell-mediated pathways form the cornerstone of relapse prevention. The rarity of these disorders continues to challenge the conduct of large, rigorous therapeutic trials. Nonetheless, innovative targeted therapies have already been developed and transformed the therapeutic landscape in NMOSD while more off-label approaches are being investigating in MOGAD. This review synthesizes current evidence on established and investigational therapies in NMOSD and MOGAD, providing an updated framework to inform clinical practice and guide future research in these complex, antibody-mediated CNS disorders.