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Fatigue that wouldn’t lift. He was still on the biologic. Still
compliant. But his body was no longer responding.

His care team followed the algorithm. They escalated the
dose. Shortened the interval. When that failed, they added
an immunosuppressant. And when that failed, they
switched him to another biologic in the same class.

No one mentioned the word tolerization. No one tested for
anti-drug antibodies.

By the time he was referred to a tertiary care center, the
pattern was clear: he had developed high-titer anti-drug
antibodies. The biologic had been neutralized—his immune
system had quietly rejected the therapy months earlier, and
he had spent the better part of a year receiving an
expensive, ineffective drug.

And yet, at no point in that year had the system paused to
ask: Why isn’t the drug working anymore?

The answer wasn’t mysterious. It was measurable. But the
test wasn’t ordered. The protocol didn’t require it. And the
economic engine had no reason to slow down. He was
switched again—to a third-line therapy—now with more
advanced disease, a narrower range of options, and a
deeper skepticism about the promise of modern medicine.

This case, documented in Clinical and Translational
Gastroenterology in 2024, is not rare. It is representative.
It’s what happens when a biologic failure is treated not as a
failure, but as routine. When switching therapies replaces
solving the problem. When ADA testing is treated as
optional, even when immune rejection is suspected. When
the system chooses workarounds over root cause.

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