CMSC 2026 registry data showed low relapse rates and no new safety signals among adults with AQP4-positive NMOSD treated with eculizumab or ravulizumab in real-world practice.
Real-world findings from the global NMO SPOTLIGHT Registry suggest that complement C5 inhibition with eculizumab (Soliris; Alexion) or ravulizumab (Ultomiris; Alexion) was associated with substantial relapse reduction in adults with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-Ab+ NMOSD), with no meningococcal infections reported.¹
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In the year before starting an Alexion C5 inhibitor, 21 patients (37.5%) experienced 28 relapses, corresponding to an annualized relapse rate (ARR) of 0.50 (95% CI, 0.33-0.72). While receiving eculizumab or ravulizumab, 3 patients (5.4%) had relapses, with ARR reduced to 0.02 (95% CI, 0.00-0.05); no patient experienced more than 1 relapse on treatment.
The registry also included 15 patients who switched from rituximab to a C5 inhibitor. In the year before initiating eculizumab or ravulizumab, 6 of these patients (40.0%) had 7 relapses, for an ARR of 0.47 (95% CI, 0.19-0.96). After switching, none experienced a relapse while on C5 inhibitor therapy.
“These results demonstrate the strong clinical benefit of eculizumab and ravulizumab in relapse prevention,” lead author Elias Sotirchos, MD, associate professor of neurology at Johns Hopkins, and colleagues wrote.1 “No new safety signals were detected; no meningococcal infections were reported.”
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Eculizumab became the first FDA-approved therapy for AQP4-Ab+ NMOSD in 2019, a milestone that shifted care from largely off-label relapse prevention strategies toward targeted biologic therapies.² Its approval was supported by the phase 3 PREVENT trial, published in The New England Journal of Medicine, in which adjudicated relapses occurred in 3 of 96 patients treated with eculizumab compared with 20 of 47 patients receiving placebo (HR, 0.06; 95% CI, 0.02-0.20; P <.001).³
Ravulizumab, also a terminal complement C5 inhibitor, was approved by the FDA in March 2024 for adults with AQP4-Ab+ NMOSD.⁴ The approval was based on the phase 3 CHAMPION-NMOSD trial, which evaluated ravulizumab in an open-label, externally placebo-controlled design using the placebo arm from PREVENT as comparator. In CHAMPION-NMOSD, ravulizumab significantly reduced relapse risk, with no adjudicated relapses observed during the primary treatment period.⁵
Although both therapies inhibit terminal complement activation at C5, they differ meaningfully in dosing burden. Eculizumab is administered intravenously every 2 weeks after induction, whereas ravulizumab was engineered for extended half-life and is administered by weight-based intravenous dosing every 8 weeks after loading, offering a less frequent maintenance schedule. Both therapies carry boxed warnings for serious meningococcal infections, and prescribing information calls for meningococcal vaccination before treatment unless the risks of delaying therapy outweigh infection risk.6,7
In the NMO SPOTLIGHT analysis, 52 patients (92.9%) received at least 1 meningococcal vaccination from the year before C5 inhibitor initiation through registry enrollment. Investigators reported no receipt of meningococcal or other vaccination in the 4 weeks before relapse and no meningococcal infections overall.¹
For clinicians, the registry findings add real-world support to the relapse-prevention effects observed in pivotal trials, while also reflecting treatment patterns that include switching from B-cell depletion to complement inhibition. Given the attack-related disability burden in AQP4-Ab+ NMOSD, sustained relapse prevention remains the central treatment goal.
