Therapeutic Drug Monitoring (TDM)

Therapeutic drug monitoring uses blood tests to measure biologic drug levels and anti‑drug antibodies. The goal is to see whether under-dosing, immune reactions, or a mismatch of drug mechanism explains ongoing inflammation. Results help decide whether to adjust the dose, shorten the interval, add an immunomodulator, or switch therapies. TDM fits within treat‑to‑target plans and is most established for anti‑TNF medicines.

Key takeaways

• Reactive TDM is recommended for people with active inflammation while on an anti‑TNF. Proactive TDM in adults is debated, though evidence is growing. (gastro.org)

• Common anti‑TNF maintenance trough goals: infliximab ≥5 µg/mL, adalimumab ≥7.5 µg/mL, certolizumab ≥20 µg/mL. Targets may be higher for complex disease. (gastro.org)

• Low drug with no antibodies suggests under‑dosing. Low drug with high antibodies suggests immune‑mediated clearance. Normal drug with active disease suggests mechanistic failure. (jdc.jefferson.edu)

• For vedolizumab and ustekinumab, immunogenicity is low, and useful target levels are less certain. Higher levels during induction and maintenance often track with better outcomes. (pubmed.ncbi.nlm.nih.gov)

• Draw TDM as a trough sample, right before the next dose. Assay type matters, especially for antibody detection. (pubmed.ncbi.nlm.nih.gov)

What TDM measures and why it matters

TDM looks at two things:

• The trough drug level, the concentration just before the next dose.

• Anti‑drug antibodies, which can bind and clear the medicine.

These results sort inadequate response into three groups:

• Pharmacokinetic failure, not enough drug exposure.

• Immune‑mediated failure, antibodies accelerating drug clearance.

• Mechanistic failure, adequate drug exposure but the drug’s pathway is not controlling inflammation.

Using this framework helps choose between dose optimization, adding an immunomodulator, or switching within or out of class. (jdc.jefferson.edu)

When to use TDM

• Reactive use: when there is confirmed active inflammation on labs, imaging, or endoscopy while on therapy. This is recommended for anti‑TNFs and commonly applied to other biologics. (gastro.org)

• Proactive use: checking levels on a schedule to keep a target range. Adult evidence is mixed, though meta‑analysis suggests fewer failures and hospitalizations. Pediatric trials support proactive TDM for adalimumab and infliximab. (pubmed.ncbi.nlm.nih.gov)

How testing is done

• Timing: draw at trough, immediately before the next dose or infusion.

• Reflex approach: many labs measure the drug first, then antibodies if the level is low or undetectable.

• Assays: drug‑tolerant antibody assays detect more antibodies than older drug‑sensitive methods, which affects interpretation. Results from different labs may not be interchangeable. (pubmed.ncbi.nlm.nih.gov)

Interpreting results: common action steps

• Low drug, antibodies absent or low: increase dose or shorten dosing interval. Consider checking adherence, weight changes, or interactions.

• Low drug, antibodies high: switch within class or add an immunomodulator if appropriate. Some antibodies are transient; repeat if the clinical picture allows.

• Therapeutic drug level, active inflammation: switch out of class, since the mechanism may not fit the disease biology. Many experts avoid abandoning an anti‑TNF until troughs exceed about 10 to 15 µg/mL. (journals.lww.com)

Common targets and notes

Note: Targets vary by assay, disease location, and outcome chosen. Always interpret alongside symptoms, biomarkers, and endoscopy.

What is known for specific biologics

• Anti‑TNFs: Reactive TDM improves decision‑making and may save costs. AGA suggests target troughs of infliximab ≥5 µg/mL, adalimumab ≥7.5 µg/mL, and certolizumab ≥20 µg/mL during maintenance. (gastro.org)

• Vedolizumab: Higher early levels predict better outcomes, and maintenance >12 µg/mL is often associated with remission, especially in ulcerative colitis. Antibodies are reported in about 1 to 3 percent on maintenance. (pubmed.ncbi.nlm.nih.gov)

• Ustekinumab: Observational data link maintenance troughs above roughly 2 to 5 µg/mL with higher rates of mucosal healing. Immunogenicity appears low in large datasets. (pubmed.ncbi.nlm.nih.gov)

Special points and limits

• Pediatric care: Proactive TDM of adalimumab and infliximab has shown better outcomes in randomized pediatric trials. Pediatric targets may differ. (academic.oup.com)

• Combination therapy: Adding a thiopurine or methotrexate can reduce antibody formation to anti‑TNFs in some cases, but risks and benefits should be weighed. (pubmed.ncbi.nlm.nih.gov)

• Assay variability: Use the same lab when possible. Document whether antibody testing is drug‑tolerant. (mdpi.com)

FAQs

When should blood be drawn for a trough level

Right before the next scheduled dose or infusion. For subcutaneous drugs, draw on the dosing day, before injection. (gastro.org)

What if symptoms are present but the trough level is “good”

That pattern points to mechanistic failure. Consider switching to a drug with a different pathway. Confirm active inflammation first. (jdc.jefferson.edu)

Do vedolizumab and ustekinumab need routine TDM

Not routinely. Evidence is growing, but clear targets and outcome‑driven strategies are not yet standardized. Use reactive TDM for loss of response. (pubmed.ncbi.nlm.nih.gov)

Can antibodies go away

Some are transient. If the clinical situation allows, repeat testing can clarify whether antibodies persist and guide next steps. (pubmed.ncbi.nlm.nih.gov)