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mechanism of action entirely (e.g., from anti-TNF to IL-17
blockade). But switching isn’t a clean reset. Cross-reactive
antibodies, immune memory, and shared epitopes
between biologics mean that the immune system is now
primed—not just to reject this drug, but potentially the
next one too.
This pattern may unfold over months or years, but in
many cases, tolerization sets in far sooner than the medical
community admits—within 6 to 18 months of treatment
initiation.
Why This Matters
If biologics were cheap, quick, and easy to replace,
tolerization might be a manageable inconvenience. But they
are none of those things.
• Biologics are expensive (often exceeding $100,000
per year).
• They are slow to produce and customize.
• And most importantly, each instance of
tolerization narrows the treatment window, as
the immune system becomes more sensitized and
resistant to similar therapies.
This makes tolerization not just a biological problem, but a
strategic threat to the future of chronic disease
management.
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