Therapeutic Drug Monitoring (TDM)

Therapeutic drug monitoring (TDM) uses blood tests to measure levels of biologic medicines and antibodies against them. In IBD, this information helps explain why a biologic is or is not working and guides choices about dose changes or switching medicines. TDM is most established for anti‑TNF biologics and is increasingly used as part of treat‑to‑target care in Crohn’s disease and ulcerative colitis. (crohnscolitisfoundation.org)

Key Takeaways

• TDM measures trough drug levels (the lowest level before the next dose) and anti‑drug antibodies in the blood.

• Reactive TDM is done when symptoms or markers worsen and is widely used to guide dose changes or switching. (crohnscolitisfoundation.org)

• Proactive TDM is regular testing in people who feel well, aiming to keep levels in a target range and prevent loss of response. (pubmed.ncbi.nlm.nih.gov)

• For anti‑TNF drugs, appropriate drug levels are linked with better remission rates and fewer hospitalizations or surgeries. (pubmed.ncbi.nlm.nih.gov)

• Results are interpreted together with symptoms, stool tests, blood markers, and scopes, not in isolation.

• TDM is not yet standardized for every biologic, and “ideal” target levels can differ between drugs and laboratories. (elsevier.es)

What is therapeutic drug monitoring?

Therapeutic drug monitoring (TDM) means checking the amount of a medicine in the blood and, for biologics, checking whether the body has made antibodies against the drug.

In IBD, this is most often used with anti‑TNF biologics such as infliximab and adalimumab. There is growing, but less complete, experience with other biologics like vedolizumab and ustekinumab. (crohnscolitisfoundation.org)

The key number is the trough level. This is the drug level measured right before the next dose, when the level is at its lowest. Many studies have shown a link between higher trough levels within a certain range and better IBD control. (crohnscolitisfoundation.org)

A typical TDM test can report:

• Trough drug concentration.

• Whether anti‑drug antibodies are present.

• Sometimes, the strength or titer of those antibodies.

Why TDM matters in IBD care

Even with modern biologics, not everyone responds the same way:

• About one third of people starting an anti‑TNF may never respond well (primary non‑response).

• Up to half can lose response over time after an initial benefit (secondary loss of response). (elsevier.es)

There are several reasons for this:

• The body may clear the drug too quickly, so levels never stay high enough.

• The immune system may form antibodies that neutralize or remove the drug.

• The inflammation may be driven by pathways that the drug does not target. (elsevier.es)

TDM helps the care team sort these possibilities. It can:

• Identify people who might do better with a higher dose or shorter interval.

• Show when a drug has likely “failed” mechanistically, so a switch to a different mechanism makes more sense.

• Avoid unnecessary dose increases when levels are already high, which can reduce cost and possibly side effects. (crohnscolitisfoundation.org)

Reactive vs proactive TDM

Reactive TDM

Reactive TDM is performed when there is a problem, such as:

• No improvement after starting a biologic.

• Return of symptoms after doing well.

• Rising fecal calprotectin, CRP, or worrisome scope findings.

Reactive TDM is now widely accepted, especially for anti‑TNF drugs. Guidelines and expert groups recommend it to guide dose escalation or switching rather than guessing. (crohnscolitisfoundation.org)

Proactive TDM

Proactive TDM means checking trough levels and antibodies on a schedule, even when symptoms are quiet. The goal is to keep levels within a target range to:

• Maintain remission.

• Prevent future loss of response.

• Possibly reduce infusion reactions and hospitalizations. (pubmed.ncbi.nlm.nih.gov)

Several trials and meta‑analyses suggest that proactive TDM of anti‑TNF drugs can:

• Reduce treatment failure.

• Improve long‑term durability of therapy.

• Reduce IBD‑related hospital stays and surgeries. (pubmed.ncbi.nlm.nih.gov)

However, evidence is not identical across studies, and professional societies differ on how strongly they endorse routine proactive TDM for every patient. Many centers use it most in high‑risk situations, such as severe ulcerative colitis, fistulizing Crohn’s disease, children, or combination‑therapy de‑escalation. (pubmed.ncbi.nlm.nih.gov)

How a TDM visit usually works

A TDM assessment is usually simple and fits into a regular clinic or infusion visit:

1. Timing is planned so the blood draw happens just before the next infusion or injection.

2. A clinician checks symptoms, recent labs, and sometimes stool tests like fecal calprotectin.

3. Blood is drawn for drug level and antibody testing, often along with routine labs.

4. The sample goes to a specialized lab; results return in days to weeks.

5. The care team reviews the results and may adjust dose, interval, or medication choice. (crohnscolitisfoundation.org)

Different laboratories use different assays, so exact numeric “targets” can vary, and many published ranges are based on specific test methods. This is one reason interpretation is best done by an IBD‑experienced clinician. (elsevier.es)

Interpreting common TDM patterns

TDM results are never read alone. They are combined with symptoms, stool markers, blood tests, and imaging or endoscopy. Still, some patterns are very common.

These are broad patterns seen in guidelines and expert algorithms, not fixed rules for any one person. (crohnscolitisfoundation.org)

Which medicines use TDM?

TDM is most established for:

• Anti‑TNF biologics such as infliximab and adalimumab.

• To a lesser extent, certolizumab pegol and golimumab.

For these drugs, exposure–response relationships and suggested trough ranges have been described in many studies and clinical reviews. (crohnscolitisfoundation.org)

For other biologics:

• Vedolizumab and ustekinumab also show a link between higher drug levels and better outcomes, but target ranges and the role of routine TDM are less clear. (elsevier.es)

• Some centers use TDM for these agents in difficult cases, but it is not as standardized as for anti‑TNF drugs.

A similar idea is used for some older immune‑suppressing drugs. For example, thiopurine metabolite testing helps find a dose that is effective but not toxic. This is usually covered in separate guidance, since it involves different tests and decisions.

Limits, costs, and practical issues

TDM is a powerful tool, but it has limits:

• Not all hospitals have on‑site assays; samples may be sent out, which slows decisions.

• Different tests can give slightly different numeric results, and published target ranges may not match every lab. (elsevier.es)

• Insurance coverage and out‑of‑pocket cost vary by region and plan.

• For some biologics, evidence is still emerging, so clinicians may disagree on when and how often to test. (pubmed.ncbi.nlm.nih.gov)

Despite these limits, TDM is becoming a routine part of modern IBD care for many people on biologics. Used thoughtfully, it helps care teams personalize dosing, avoid unnecessary medication changes, and support long‑term remission. (pubmed.ncbi.nlm.nih.gov)

FAQs

Is TDM a one‑time test or something repeated?

TDM is often repeated at key moments: after induction, when there is loss of response, and sometimes at regular intervals during stable maintenance for high‑risk patients. The schedule depends on the drug, disease severity, and local practice patterns. (crohnscolitisfoundation.org)

Can TDM replace colonoscopies or stool tests?

No. TDM answers a different question: whether enough drug is present and whether antibodies are a problem. Scopes, imaging, and stool markers like fecal calprotectin are still needed to see how active the disease is and whether treatment targets, such as mucosal healing, are being met. (crohnscolitisfoundation.org)