Page 17 - Binder2

The Hidden Timeline of Decline

Tolerization typically follows a three-stage timeline:

1. Initial Success (The Honeymoon Period)

When a biologic is first introduced, the response can be
profound. Inflammatory markers drop, symptoms recede,
and patients often feel a rapid return to function and quality
of life. For autoimmune patients, it can mean the first full
night of sleep in months. For cancer patients, it might mean
visible tumor regression. For rare disease patients, enzyme
therapies start breaking down the very substrates that
previously poisoned their cells.

This period is often marked by hope, relief, and
optimism—for both patients and providers. It’s also when
trust in the drug, and in the system that delivered it, begins
to build.

But while everything seems to be improving on the surface,
the immune system may already be quietly reacting. It
begins to identify the biologic as “non-self.” Dendritic cells
present fragments to T-helper cells. B-cells begin the
process of differentiating into plasma cells. And although
there are no obvious clinical symptoms yet, the countdown
has begun.

2. Subclinical Rejection (The Gray Zone)

This is the most dangerous and least visible stage. Anti-
drug antibodies (ADAs) begin to form, but their effects are
subtle. Blood levels of the drug may drop. The half-life

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