Anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-Ab+ NMOSD) is a rare autoimmune disease of the central nervous system (CNS) characterized by repeated, unpredictable relapses that may lead to irreversible neurological disability accumulation.¹ Alexion complement component 5 inhibitor therapies (ALXN-C5ITs), including eculizumab and ravulizumab, are approved in multiple countries for the treatment of AQP4-Ab+ NMOSD.¹ Despite phase 3 studies demonstrating marked relapse risk reductions with eculizumab and ravulizumab, long-term evidence from routine clinical practice remains limited.¹ At the AAN Annual Meeting 2026, Dr. Ahmed Obeidat from the Medical College of Wisconsin, United States, presented findings from the NMO SPOTLIGHT Registry, demonstrating the strong clinical benefit of eculizumab and ravulizumab in relapse prevention among patients with AQP4-Ab+ NMOSD.¹

The ongoing global NMO SPOTLIGHT Registry is an ambispective, observational study with up to 5 years of follow-up evaluating patients with AQP4-Ab+ NMOSD treated with ALXN-C5ITs, including eculizumab and ravulizumab.¹ The Registry aimed to evaluate patient characteristics and clinical outcomes associated with ALXN-C5ITs while contributing to the growing body of real-world evidence and informing clinical practice.¹ Data collected between August 30, 2023, and October 14, 2024, included 1 year of retrospective medical chart review followed by prospective longitudinal follow-up after Registry enrollment.¹ Retrospective data collection included demographics, comorbidities, relapse history, treatment patterns, healthcare resource utilization, and vaccination history, while prospective data included safety and patient-reported outcomes.¹

Both retrospective and prospective assessments evaluated clinical effectiveness outcomes, resource utilization, acute relapse treatments including intravenous (IV) corticosteroids and plasma exchange, concomitant therapies, and vaccination status.¹ Physician-reported relapses were defined as new or worsening neurological symptoms persisting for >24 hours, preceded by ≥30 days of clinical stability, and requiring acute treatment with high-dose IV corticosteroids, plasma exchange, or IV immunoglobulin.¹ Analyses were performed in both the overall Registry population and the subgroup of patients who switched from rituximab to ALXN-C5IT therapy.¹

Baseline demographic characteristics were generally consistent with the known epidemiology of AQP4-Ab+ NMOSD.¹ The median age at enrollment was in the mid-50s, and approximately 90% of patients were female.¹ The Registry also demonstrated broad racial representation, including African American, White, and Asian patients.¹ Exposure duration was longer for eculizumab than ravulizumab, likely reflecting the earlier clinical availability of eculizumab.¹

In the overall Registry population, 21 of 56 patients (37.5%) experienced a total of 28 relapses during the year prior to ALXN-C5ITs initiation, corresponding to an annualized relapse rate (ARR) of 0.50 over 56.1 patient-years.¹ Acute myelitis and optic neuritis were the most common relapse types.¹ Following ALXN-C5ITs initiation, ARR decreased markedly from 0.50 to 0.02 over a median treatment exposure duration of 40.3 months, with only 3 of 56 patients (5.4%) experiencing a total of 3 relapses over 181.9 patient-years.¹ Notably, no patients experienced more than 1 relapse during treatment, and no relapses occurred among patients receiving ravulizumab.¹ These findings support the real-world effectiveness of ALXN-C5ITs in preventing relapses among patients with AQP4-Ab+ NMOSD.¹

Similarly, among patients who switched from rituximab to ALXN-C5ITs, 6 of 15 patients (40.0%) experienced 7 relapses during the year prior to treatment initiation, corresponding to an ARR of 0.47 over 15.0 patient-years.¹ Following the switch to ALXN-C5ITs, no relapses were reported during a median treatment exposure duration of 40.0 months, suggesting that switching from rituximab to eculizumab or ravulizumab may provide additional relapse control in selected patients with persistent disease activity.¹

The study also evaluated concomitant NMOSD therapy use before and during ALXN-C5ITs treatment.¹ During the year prior to treatment initiation, 73.2% of patients received additional NMOSD therapies, including corticosteroids, rituximab, and other immunosuppressive treatments.¹ While receiving ALXN-C5ITs, only 33.9% of patients continued concomitant treatments, indicating that many patients maintained disease control without requiring multiple additional therapies.¹

Safety findings were consistent with previous clinical trial data.¹ Most patients received meningococcal vaccination prior to or during treatment, and no relapses occurred within 4 weeks following vaccination.¹ 8.9% patients experienced serious adverse events; however, none were considered related to ALXN-C5ITs.¹ Importantly, no meningococcal infections or deaths were reported during the observation period.¹

In summary, findings from the global NMO SPOTLIGHT Registry demonstrated that eculizumab and ravulizumab were associated with marked reductions in relapse activity in real-world patients with AQP4-Ab+ NMOSD, both in the overall Registry population and among patients who switched from rituximab therapy.¹ The favorable long-term safety profile and reduced need for concomitant immunosuppressive therapies further support the growing role of ALXN-C5ITs as an effective relapse prevention strategy in AQP4-Ab+ NMOSD.¹