視神経脊髄炎スペクトラム障害の最新治療

抄録

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune disease of the central nervous system characterized by the presence of anti–aquaporin 4 (AQP4) antibodies targeting astrocytes. Recurrent attacks often lead to irreversible disability, making relapse prevention a central goal of treatment. Traditionally, glucocorticoid and oral immunosuppressants have been used, yet they are limited by insufficient efficacy and possible cumulative toxicity. In recent years, advances in understanding NMOSD pathophysiology have led to the development of biologics targeting key immune pathways. Complement C5 inhibitors (eculizumab, ravulizumab) effectively block antibody–mediated complement activation, demonstrating near–complete prevention of relapses. B–cell–depleting agents (rituximab, inebilizumab) suppress multiple pathogenic aspects of B cells, such as antibody production, antigen presentation, and proinflammatory cytokine release, substantially reducing relapse risk. Interleukin–6 receptor blockade with satralizumab inhibits broad spectrum of pathology including plasmablast survival, Th17 cell differentiation, and blood–brain barrier disruption, achieving significant relapse reduction with the advantage of subcutaneous self–administration. Each agent carries unique safety considerations : severe meningococcal infection requiring emergency medical care with complement inhibitors, hypogammaglobulinemia and possible long–term increase in serious infection rate with B–cell depletion, and risk of masking severe infections due to suppressed fever with IL–6 receptor blockade. The choice of therapy requires individualized assessment of disease severity, comorbidities, infection risk, and patient lifestyle. Biologics now allow clinicians to realistically aim for “zero relapses,” but challenges remain, including identification of predictive biomarkers, long–term safety, and cost–effectiveness. Future registry studies and real–world evidence will be essential to optimize treatment strategies.