This study looks at anti-drug antibodies against natalizumab and suggests that loss of efficacy is one of the better predictors of the response, but suggests that looking for ADA after a suspicious event is better than routine testing.
They did this study because of a case of severe disease activity after 10 infusions of natalizumab, despite no clinical or radiological activity at 6 months.
They looked at 6 months, 12 months and 18 months after delivery and say ADA are uncommon.
This not true infact they are incredibly common, and occur in over 80% of people but it just depends on how and when you look and what you report and here they are using an assay that fails to identify and/or ignores positive samples and further more it is not within 12 infusions i.e. twelve months when they are common it is actually 12 weeks and with time you lose the anti-drug antibody response. So by looking at 6 months you have missed most of the action. If Sandoz released the data from their trials one could show this really well because they took samples at 0, 4, 8 and 12 weeks. However, we know the punch line because it is in the unpublished public domain. However Biogen took samples at 0, 12, 24, 36 72 etc and if you look at this you can get a sense of what happens. Prof Angry and team have shown this.
Testing for ADA has a significant cost but it can be done if you have the assay…however we will show that you can sort of get the answer in a much easier way. Watch this space.
Levy M, Beigneux Y, Roux T, Mossad M, Ricigliano V, Senant M, Papeix C, Stankoff B, Louapre C, Maillart E, Lazzarotto A. Clinical relevance and predictors of anti-natalizumab antibodies in multiple sclerosis: A real-world retrospective cohort study. Mult Scler J Exp Transl Clin. 2026 Mar 30;12(1):20552173261438267. doi: 10.1177/20552173261438267.
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….; predictors were assessed…..
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)….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.
Source: multiple-sclerosis-research.org