Therapeutic drug monitoring in inflammatory diseases and cancer

Therapeutic drug monitoring is a key tool of personalized medicine for the continually growing range of biologic therapies. Fully automated chemiluminescence immunoassays (ChLIAs) and ELISAs from Euroimmun enable efficient measurement of drug levels and anti-drug antibodies in patient sera, supporting decision-making on the therapy type, dosage and timing.

Precision therapies

Biologics are commonly used to treat inflammatory conditions such as inflammatory bowel disease (IBD), rheumatoid arthritis, spondyloarthritis, psoriasis and multiple sclerosis, as well as various cancers. However, treatment responses can vary significantly, with many patients experiencing either no benefit or waning effects over time. Dramatic loss of response can occur when patients produce anti-drug antibodies, which neutralize the biologic or accelerate its clearance.

Advantages of monitoring

Therapeutic drug monitoring (TDM) is the process of measuring drug concentrations and anti-drug antibodies in a patient’s bloodstream to determine whether drug levels fall within the therapeutic window. Levels below the therapeutic range can impair treatment effectiveness, while levels above it could cause side effects. Using TDM results, clinicians can tailor treatment by modifying the medication type, dose, or administration schedule, thus enabling a more individualized approach¹.

TDM can be performed reactively or proactively. Reactive TDM is triggered by clinical signs indicating a lack or loss of response and aids in identifying the cause of treatment failure. In contrast, proactive TDM involves routine testing at set intervals regardless of symptoms, with the goal of preventing treatment failure and avoiding disease exacerbations.

Inflammatory bowel diseases

Reactive TDM is a widely accepted clinical strategy for addressing treatment failure in IBD patients undergoing anti-TNFα therapy, and it is endorsed by most gastroenterology societies². This method has demonstrated greater cost-effectiveness compared to the traditional approach of empiric dose escalation, thereby aiding efficient allocation of resources for these costly treatments¹.

Proactive TDM is a newer strategy that has been integrated into clinical practice to varying extents across different countries ^2,3. For instance, the Australian guideline for anti-TNFα therapy in IBD recommends TDM after successful treatment induction, before a planned drug holiday, during clinical remission when the results may influence management decisions, as well as in cases of treatment failure⁴.

Pooled recommendations

Evidence suggests that the effects of TDM are consistent across various immune-mediated inflammatory diseases^3,5,6. In the BMJ clinical practice guideline, recommendations for IBD, rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, and psoriasis are pooled, with proactive TDM advised for patients receiving intravenous infliximab. This strategy has been shown to improve the chances of maintaining long-term disease control or remission compared to standard care^3,5,6. Recommendations for further drugs are pending further clinical trial data. Proactive TDM may be particularly beneficial for patients exhibiting factors linked to a poorer prognosis or a higher likelihood of hospitalization or surgery³.

Multiple sclerosis and cancer

Biologic therapies are an important treatment option in multiple sclerosis. Natalizumab is a therapeutic agent that blocks α4β1-integrin and prevents leukocyte migration across the blood-brain barrier⁷, while ocrelizumab targets CD20 and promotes selective depletion of disease-promoting B cells⁹.

Monoclonal antibody therapies for cancer act via various molecular mechanisms^10,11. Anti-CD20 therapies facilitate selective depletion of malignant B cells in non-Hodgkin’s lymphoma. Other therapeutic agents target antigens that are overexpressed on solid tumors, for example human epithelial growth factor receptor 2 (HER2), or proteins that are involved in angiogenesis, such as vascular endothelial growth factor (VEGF).

Immune checkpoint inhibitors like programmed death receptor-1 (PD-1) enhance T cell ability to recognize and destroy tumor cells. Despite their effectiveness, antibody therapies may be suboptimally dosed in some patients due to pharmacokinetic variability. TDM is a promising strategy to individualize dosing and optimize outcomes in oncology.

Efficient TDM measurements

Immunoassays provide fast and simple quantification of drug concentrations and anti-drug antibodies in serum or plasma and are widely used in clinical routine. ELISA is the most commonly used method and is valued for its scalability and cost-effectiveness. ELISAs can be performed manually or on fully automated systems, thus accommodating different testing volumes. Chemiluminescence immunoassays (ChLIAs) provide higher sensitivity, faster turnaround times and random-access automation, making them ideal for high-throughput clinical use.

Extensive assay range

A large portfolio of ELISAs and ChLIAs for measuring drug levels and anti-drug antibodies in patient serum or plasma has been developed by Biosynex-Theradiag and is available from Euroimmun and Immunodiagnostic Systems (both part of Revvity). The assays are designed with clinically relevant dynamic ranges and are suitable for monitoring drug levels during both induction and maintenance phases of therapy. They can be used with both the original drugs and biosimilars. Biosynex-Theradiag assays are backed up by numerous studies published in peer-reviewed journals¹².

The LISA TRACKER* range covers the therapies adalimumab, infliximab, etanercept, certolizumab, golimumab, rituximab, secukinumab, tocilizumab, ustekinumab, vedolizumab, bevacizumab and trastuzumab. The i-Tracker ChLIA* range includes adalimumab, infliximab, etanercept, certolizumab, golimumab, rituximab, tocilizumab, ustekinumab, vedolizumab, risankizumab and ocrelizumab. In addition, ChLIAs for natalizumab, nivolumab and pembrolizumab are available for research use only.

The assays for adalimumab, infliximab, and etanercept are calibrated using the 1st WHO International Reference Standards, ensuring consistency and comparability of results. Additionally, ready-to-use internal quality control sera (IMMUNO-TROLs*) are offered to support accurate determination of biotherapy dosing.

Summary

• TDM supports a personalized approach to treatment with biologic therapies
  Maintaining serum drug levels within the therapeutic window aids in improving clinical outcomes.
• Levels of drugs and anti-drug antibodies can be measured quickly and efficiently using fully automated ChLIAs and ELISAs.
• Euroimmun offers an extensive range of TDM assays for biologics used in the treatment of inflammatory diseases and cancer.

* Products are manufactured by Biosynex SA. Regulatory status, precise intended use and product availability must be verified for the user’s individual jurisdiction.

References

1. Albader F, Golovics PA, Gonczi L et al. Therapeutic drug monitoring in inflammatory bowel disease: The dawn of reactive monitoring World J Gastroenterol. Oct 7, 2021; 27(37): 6231–6247. doi: 10.3748/wjg.v27.i37.6231
2. Shmais M, Regueiro M, Hashash JG. Proactive versus Reactive Therapeutic Drug Monitoring: Why, When, and How? Inflamm Intest Dis. 2021 Sep 6;7(1):50–58. doi: 10.1159/000518755.
3. Kawano-Dourado L, Kristianslund EK, Zeraatkar D et al. Proactive therapeutic drug monitoring of biologic drugs in adult patients with inflammatory bowel disease, inflammatory arthritis, or psoriasis: a clinical practice guideline BMJ 2024;387:e079830. doi.org/10.1136/bmj-2024-079830
4. Mitrev N, Vande Casteele N, Seow CH et al. IBD Sydney Organisation and the Australian Inflammatory Bowel Diseases Consensus Working Group. Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases. Aliment Pharmacol Ther. 2017 Dec;46(11–12):1037-1053. doi: 10.1111/apt.14368.
5. Chanchlani N, Yiu ZZN, Stamp LK, Day AS. Therapeutic drug monitoring for immune mediated inflammatory diseases. BMJ Med. 2024 Oct 28;3(1):e001130. doi: 10.1136/bmjmed-2024-001130
6. Zeraatkar D, Pitre TS, Kirsh S, et al. Proactive therapeutic drug monitoring of biologic drugs in patients with inflammatory bowel disease, inflammatory arthritis, and psoriasis: systematic review and meta-analysis. BMJ Med. 2024 Oct 28;3(1):e000998. doi: 10.1136/bmjmed-2024-000998.
7. Khoy K, Mariotte D, Defer G, et al. Natalizumab in Multiple Sclerosis Treatment: From Biological Effects to Immune Monitoring. Front Immunol. 2020 Sep 24;11:549842. doi: 10.3389/fimmu.2020.549842.
8. Toorop AA, van Lierop ZY, Gelissen LM et al. Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS). J Neurol Neurosurg Psychiatry. 2024 Apr 12;95(5):392-400. doi: 10.1136/jnnp-2023-332119.
9. Carlson AK, Amin M, Cohen JA. Drugs Targeting CD20 in Multiple Sclerosis: Pharmacology, Efficacy, Safety, and Tolerability. Drugs. 2024 Mar;84(3):285-304. doi: 10.1007/s40265-024-02011-w.
10. Zahavi D, Weiner L. Monoclonal Antibodies in Cancer Therapy. Antibodies (Basel). 2020 Jul 20;9(3):34. doi: 10.3390/antib9030034.
11. Justiz-Vaillant A, Pandit BR, Unakal C et al. A Comprehensive Review About the Use of Monoclonal Antibodies in Cancer Therapy. Antibodies 2025, 14, 35. https://doi.org/10.3390/ antib14020035
12. Tracker Publications. Biosynex Theradiag. www.theradiag.com/en/theranostic-2/therapeutic-drug-monitoring-biologics/publications-2/