Clinical relevance and predictors of anti-natalizumab antibodies in multiple sclerosis: A real-world retrospective cohort study

Background Natalizumab is effective for relapsing MS but may trigger anti-natalizumab antibodies (ANZ) that neutralise drug activity and increase reactions. Trials report persistent antibodies in ∼6% and overall prevalence between 4% and 14%, but real-world burden and optimal testing remain uncertain. We assessed ANZ prevalence, timing, and correlates, comparing systematic with indication-driven testing. Methods Single-centre retrospective cohort of natalizumab-treated patients with ≥1 ANZ test. Testing followed routine care: systematic screening at months 6/12/18 or testing triggered by suspected inefficacy or infusion reactions. Clinical/MRI data were abstracted; time to positivity was used in Kaplan–Meier; predictors were assessed using multivariable logistic regression. Results Among 182 patients (348 tests), ANZ were detected in nine (4.9%; four persistent and five transient), all within the first 12 infusions. Positivity differed by indication ( p = 0.005): suspected inefficacy 10.5% (4/38), systematic screening 1.6% (5/304), post-reaction testing 0% (0/6). Within suspected inefficacy, MRI activity was more strongly associated with positivity than symptoms alone ( p = 0.04). In multivariable models, suspected inefficacy was the only independent predictor; adding indication improved discrimination (AUC 0.74 vs. 0.56). Conclusions In routine care, ANZ positivity is uncommon and occurs early. Indication-driven testing – especially when prompted by new MRI lesions – yields greater diagnostic value than routine screening of clinically stable patients, supporting a selective, context-driven approach to ANZ monitoring.