Biomarkers to predict relapse in myelin oligodendrocyte glycoprotein antibody-associated disease: a systematic review and meta-analysis.

Background: Detection of immunoglobulin G targeting myelin oligodendrocyte glycoprotein (MOG-IgG) is the mainstay of laboratory diagnosis of MOG antibody-associated disease. Laboratory biomarkers have the potential to predict disease course and activity, thus informing prompt therapeutic decisions to minimise relapse-associated disability accrual.

Methods: This systematic review with meta-analysis was registered in PROSPERO (CRD42024554429). MEDLINE, Embase and Scopus databases were searched. Random-effects or mixed-effects modelling was performed and OR or HR with 95% CIs reported.

Results: 106 studies with ≥1710 individuals were included. A relapsing course was associated with persistent seropositivity on serial samples collected ≥3 months apart (OR 2.7 (95% CI 1.8 to 4.0), p<0.0001), lower likelihood of seroreversion to negative status (HR 0.19 (95% CI 0.14 to 0.26), p<0.0001) and delayed seroreversion compared with monophasic participants (median 19 years vs 2.5 years, p<0.0001). Acute disseminated encephalomyelitis was associated with a non-relapsing course (OR 0.049 (95% CI 0.0029 to 0.84), p=0.037). Serum MOG-IgG titre-negative, low positive or clear positive-discriminated disease state: attack was associated with clear positive titre (OR 3.6 (95% CI 2.6 to 5.0), p<0.0001), but not negative titre (OR 0.073 (95% CI 0.028 to 0.19), p<0.0001). Cerebrospinal fluid (CSF) leucocytosis (≥5 cells/µL) was associated with attack (OR 3.1 (95% CI 1.7 to 5.9), p=0.0004). Neither serum glial fibrillary acidic protein nor neurofilament light chain correlated with disease activity. Novel biomarkers of disease course and activity have also been assessed qualitatively.

Conclusions: MOG-IgG serostatus and titre and CSF leucocytosis are biomarkers of disease course and activity. The findings provide rationale for serial serum MOG-IgG testing at an interval of 3-6 months in the first 12 months of disease to assist in relapse risk stratification.

Prospero registration number: CRD42024554429.