SPOTLIGHT Registry Findings on Eculizumab and Ravulizumab in gMG

A multinational observational analysis from the MG SPOTLIGHT Registry offers real-world insight into the clinical effectiveness and safety of the complement C5 inhibitors eculizumab and ravulizumab for patients with generalized myasthenia gravis (gMG). Published in the Journal of the Neurological Sciences in July 2025, the study underscores not only the sustained therapeutic impact of eculizumab but also the maintenance of these gains following a transition to the longer-acting agent ravulizumab.

Translating Trial Data to Clinical Practice
Eculizumab and ravulizumab, monoclonal antibodies targeting complement component 5, are approved for anti-acetylcholine receptor antibody-positive gMG based on robust trial data. However, evaluating long-term effectiveness in clinical practice requires registry-level analysis. The SPOTLIGHT Registry enrolled 189 patients from the United States and Canada, most of whom had received multiple prior therapies, with nearly half on glucocorticoids at eculizumab initiation and 78% reporting comorbidities, such as arterial hypertension,  obesity, and dyslipidemia.

Key patient-reported and physician-assessed metrics, including MG Activities of Daily Living (MG-ADL), MG Quality of Life 15-revised (MG-QOL15r), and MGFA Clinical Classification, were used to evaluate treatment effectiveness.

Significant and Sustained Functional Improvements
Eculizumab treatment resulted in a mean reduction of 4.2 points (95% CI −5.0 to −3.4) in MG-ADL scores and a 7.5-point reduction (95% CI −9.9 to −5.0) in MG-QOL15r scores, with outcomes assessed after a median of 18 months of treatment (P<0.0001 for both). Among patients with 3 available MG-ADL assessments, 34.5% achieved minimal symptom expression (MG-ADL ≤1) by first assessment—a significant increase from just 3.6% at baseline (P<0.0001). Also, 73% of patients with at least 1 documented MG-ADL assessment achieved clinically meaningful improvement in total MG-ADL score (≤2 point).

Physician assessments via MGFA classification corroborated these findings; the proportion of patients in MGFA class 0–II nearly doubled from 43.7% to 86.4% at first assessment after treatment. Together, these improvements in MG-ADL and MGFA were durable, with median follow-up durations of 38 and 39 months, respectively.

Transitioning to Ravulizumab: Benefits Maintained
Among patients who transitioned from eculizumab to ravulizumab, clinical benefits across functional status and quality of life were maintained. In those with longitudinal MG-ADL data (n=37), scores declined by an average of 4.2 points (95% CI:  –5.5 to –3.0) from pre-eculizumab to a median of 9.8 months after starting ravulizumab. Among patients assessed by MGFA class (n=34), only 26.5% were in class II, and none were in class 0–I before treatment. That proportion rose to 85.3% with eculizumab and further to 91.2% after a median of 8.7 months on ravulizumab. Additionally, MG-QOL15r scores (n=14) improved, with a mean reduction of 8.6 points (95% CI: –13.1 to –4.2) after a median of 11.4 months on ravulizumab compared to before starting eculizumab.

This maintenance of clinical benefit is noteworthy given ravulizumab’s 8-week dosing interval compared to the biweekly administration of eculizumab—a factor cited by some patients in discontinuation decisions.

Safety Profile: Consistent with Prior Studies
The safety analysis did not reveal new safety signals for either therapy. Three treatment-related serious adverse events were reported: two with eculizumab (including one fatal Aspergillus infection and one nervous system disorder) and one with ravulizumab (an anaphylactic reaction that resolved). No meningococcal infections occurred; meningococcal vaccination rate was 96.8% prior to therapy initiation.

Clinical Takeaways
Eculizumab provides improvements in both functional status and quality of life for patients with gMG, with effects sustained over multi-year follow-up. While the registry’s retrospective, observational nature and lack of a control arm introduce potential for selection and reporting bias, the findings reinforce established clinical trial outcomes. Moreover, they demonstrate that transitioning to ravulizumab, a longer-acting C5 inhibitor, maintains these therapeutic benefits in real-world practice.

Reference:
Howard JF Jr, Dodig D, Zeinali L, et al. First analysis of the Myasthenia Gravis SPOTLIGHT Registry: outcomes with eculizumab and ravulizumab. J Neurol Sci. 2025;476:123628. doi:10.1016/j.jns.2025.123628