Biomarkers for satralizumab treatment in neuromyelitis optica spectrum disorders: a prospective case series

Satralizumab reduces relapse risk in neuromyelitis optica spectrum disorder (NMOSD). However, dynamic biomarker changes during treatment have not been systematically characterized. We conducted this prospective self-controlled case series to evaluate longitudinal changes in multiple biomarkers during satralizumab treatment and identify potential indicators of disease activity and therapeutic response. We enrolled four AQP4-IgG-positive NMOSD patients receiving satralizumab for 24 months with serial blood sampling at 13 timepoints (baseline and months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, and 24). Clinical outcomes and candidate biomarkers (serum AQP4-IgG, glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL], chitinase-3-like protein 1 [CHI3L1], triggering receptor expressed on myeloid cells 2 [TREM2], IL-6, IL-6Rα, CD19+CD27+CD38+ B-cell ratio, and Treg-cell ratio) were analyzed. In the four patients, patient 3 (P3) experienced two relapses at months 1 and 7 after satralizumab treatment initiation; the remaining three patients remained relapse-free. Expanded Disability Status Scale scores in all patients were stable or improved at final follow-up. Serum AQP4-IgG, GFAP, and NfL showed trajectories parallel to satralizumab response and disease activity. CHI3L1 reflected therapeutic effects but was less sensitive than GFAP or NfL. TREM2, IL-6, and IL-6Rα showed no prominent changes. Satralizumab reduced CD19+CD27+CD38+ plasmablasts and increased Treg-cell proportion in some patients. Serum AQP4-IgG, GFAP, and NfL may be promising biomarkers of NMOSD disease activity and satralizumab treatment response. Further well-designed multicenter large-scale clinical studies are needed to validate the clinical utility of these biomarkers.