Astrocytic and Axonal Injury Biomarkers in AQP4 Antibody-Positive NMOSD: Insights From PREVENT and CHAMPION-NMOSD.

In 30 seconds

This biomarker analysis used samples from the phase 3 PREVENT and CHAMPION-NMOSD trials to assess serum GFAP and NfL in people with AQP4 antibody-positive NMOSD receiving eculizumab or ravulizumab. Samples from 41 PREVENT and 55 CHAMPION-NMOSD participants were compared with matched healthy donors. Pretreatment biomarker levels were elevated and associated with clinical features of disability. Median GFAP levels declined within 4–6 weeks and remained suppressed with both drugs; NfL declined significantly with ravulizumab but not eculizumab. In PREVENT, relapse-associated GFAP increases were attenuated with eculizumab compared with placebo.

Key findings

• Pretreatment serum GFAP and NfL were elevated in patients compared with demographically matched healthy donors.
• High baseline GFAP and NfL levels were associated with higher baseline Hauser Ambulation Index scores.
• Median GFAP declined within 4–6 weeks and remained suppressed during treatment with eculizumab or ravulizumab.
• NfL declined significantly with ravulizumab but not eculizumab; in PREVENT, eculizumab attenuated relapse-associated GFAP increases seen with placebo.

Why it matters

The findings support serum GFAP as a pharmacodynamic marker of astrocytic injury and complement C5 target engagement in AQP4-Ab+ NMOSD. NfL responses differed between the two trial treatments, so the biomarkers may reflect distinct aspects of injury or treatment response. Their associations with disability-related clinical features also suggest potential value for characterising disease activity, although the analysis does not establish their role in individual treatment decisions.

What to keep in mind

The biomarker analysis included samples from 41 PREVENT and 55 CHAMPION-NMOSD participants; GFAP and NfL were analysed retrospectively in PREVENT and prospectively in CHAMPION-NMOSD.