Threshold-Dependent Discordance Between STRATIFY JCV™ and IMMUNOWELL™ Assays in Relapsing Multiple Sclerosis

Area of Science:

• Immunology
• Neurology
• Clinical Diagnostics

Background:

• Anti-JC virus (JCV) antibody testing is crucial for stratifying progressive multifocal leukoencephalopathy (PML) risk in natalizumab-treated patients.
• STRATIFY JCV™ is the established reference assay, while IMMUNOWELL™ is gaining traction with biosimilar use.
• Understanding inter-assay variability is key for accurate risk assessment.

Purpose of the Study:

• To compare the concordance between STRATIFY JCV™ and IMMUNOWELL™ assays for anti-JCV antibody testing.
• To determine if discordance stems from biological differences or interpretation thresholds.
• To evaluate assay performance within clinically relevant PML risk categories.

Main Methods:

• A single-center observational study involving 250 relapsing multiple sclerosis (RMS) patients.
• Paired, same-day testing using STRATIFY JCV™ and IMMUNOWELL™ assays.
• Analysis of agreement using manufacturer cutoffs and clinical PML risk thresholds, with correlation and Bland-Altman analyses.

Main Results:

• Concordance was 78.0% (κ=0.55) using analytical cutoffs, with discordance in borderline ranges.
• Concordance increased to 93.2% (κ=0.73) when applying clinical risk thresholds.
• Strong correlation (r=0.922) and minimal mean bias (+0.06) were observed, with deviations mainly at lower index values.

Conclusions:

• Inter-assay discordance between STRATIFY JCV™ and IMMUNOWELL™ is primarily driven by interpretation thresholds.
• Applying clinical PML risk categories significantly improves assay concordance.
• The findings support the interchangeability of these assays for routine monitoring in the biosimilar era, with caution advised for borderline results.