Discontinuing immunotherapy in aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorder: Relapse risk and disability outcomes after treatment withdrawal

BACKGROUND: Aquaporin-4-immunoglobulin G-seropositive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD) is a relapse-associated inflammatory disease in which attacks drive irreversible disability. Treatment discontinuation occurs in practice, and data on outcomes after withdrawal are limited. METHODS: We retrospectively reviewed adults with AQP4-IgG+ NMOSD who had discontinued maintenance immunotherapy and had at least 6 months of follow-up. Clinical characteristics, treatment exposure, relapses, and disability outcomes were collected. Relapse-free survival was analysed using the Kaplan-Meier method. RESULTS: Among 292 patients with AQP4-IgG+ NMOSD, 22 met the inclusion criteria. Median age at discontinuation was 48.8 years (interquartile range [IQR] 28.9-65.5) and 19 patients (86.4%) were female. Twelve of 22 patients (54.5%) relapsed after discontinuation, whereas 10 (45.5%) remained relapse-free. The relapse-free probability was 81.0% at 1 year (95% CI, 56.9-92.4), 56.3% at 5 years (95% CI, 32.6-74.5), and 48.2% at 10 years (95% CI, 24.0-68.9). In subgroup analysis, patients who remained relapse-free had lower Expanded Disability Status Scale (EDSS) scores at nadir (4.0 [3.5-4.0] vs 5.0 [4.0-6.0], p = 0.032). EDSS scores worsened in 5 of 12 relapsing patients (41.7%) but in none of the 10 non-relapsing patients; within-group change was significant in the relapse group (p = 0.027). CONCLUSION: Maintenance immunotherapy discontinuation in AQP4-IgG+ NMOSD was associated with a high risk of relapse, frequently resulting in disability worsening. These findings emphasize the need for careful consideration before treatment withdrawal, even among patients with prolonged clinical remission.