Rituximab as First-Line Compared to Escalation Immunotherapy Is Associated With Lower Disability Accumulation in Aquaporin-4-IgG-Positive Neuromyelitis Optica Spectrum Disorder: A Multicenter Cohort Study From Germany and the United Kingdom.

BACKGROUND

Aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD) can cause significant disability after a single attack. Long-term immunotherapy reduces disability accumulation, but the choice of first-line therapy varies. In the United Kingdom, rituximab is typically used as escalation therapy after conventional immunosuppressants fail, while in Germany, it is widely used as first-line treatment.

METHODS

We compared attack risk and disability outcomes based on the Expanded Disability Status Scale (EDSS) in AQP4-IgG+ NMOSD patients treated with rituximab as first-line versus escalation therapy. Furthermore, attack suppression and risk factors for attacks in individuals who received treatment with azathioprine and mycophenolate mofetil (with/without escalating to rituximab) were analyzed.

RESULTS

The risk of attack was lower in individuals who received rituximab as first-line therapy (n = 52) compared to escalation therapy (n = 81, HR = 0.45, 95% CI = 0.30-0.67). Once escalated to rituximab, there was no altered risk of attack between first-line rituximab and escalation therapy (HR = 1.15, 95% CI = 0.64-2.08). Rituximab as first-line compared to escalation therapy was associated with lower EDSS scores at therapy start (3.0 vs. 6.0, p = 1.10 × 10-3). In patients who remained on azathioprine or mycophenolate mofetil (n = 45), age < 50 years and treatment with azathioprine were identified as risk factors for attacks.

CONCLUSIONS

Rituximab as a first-line therapy shows significant reduction in disability accumulation compared to escalation treatments. However, a subgroup of patients with AQP4-IgG+ NMOSD may still respond well to conventional immunosuppression-specifically older patients treated with mycophenolate mofetil.