Page 128 - Binder2

Key Principle Description
appearing to benefit. Extended
monitoring is necessary to detect
this delayed loss of efficacy.
Differences in assay methods
across trials (e.g., binding vs.
neutralizing antibodies, timing of
Standardized Assay sampling) prevent accurate cross-
Protocols study comparisons. Standardization
is essential for consistent
interpretation and comparison of
immunogenicity data.
ADAs affect drug behavior by
lowering serum levels, altering
Correlation of ADA clearance, or neutralizing effects.
with Clinical and Trials must transparently connect
Pharmacokinetic ADA emergence with changes in
Outcomes pharmacokinetics and loss of
clinical benefit to fully assess
immunogenicity impact.

Why does this matter?

Because anti-drug antibodies are the most visible
marker of immune rejection. They are the first and most
measurable sign that the body is no longer tolerating the
therapy. Before a flare, before a switch, before a patient
drops out of care—ADAs tell us that the immune system
has changed its mind.

Any serious conversation about immune tolerance begins
with ADAs.
They are the canary in the coalmine of biologic failure.
And yet, they remain peripheral in trial design,

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