Exploring advances in TDM for IBD management: insights from our recent webinar

Rachel Nice, Section Lead for Research and Development and Rebecca Smith, Gastroenterology Specialist Registrar, Royal Devon University Healthcare NHS Foundation Trust

Therapeutic drug monitoring (TDM) has emerged as a key strategy for optimising the treatment of inflammatory bowel disease (IBD). While biologics like infliximab (IFX) and adalimumab (ADM) work well for many patients, challenges like primary unresponsiveness and secondary loss of response (LOR) still occur. TDM strategies enable clinicians to monitor drug and anti-drug antibody (ADA) levels in patients’ bloodstreams, supporting tailored treatments and necessary dose adjustments. BIOHIT HealthCare recently sponsored a webinar, hosted by the Clinical Services Journal, that explored current and future trends in TDM for IBD management.

In this session, Rachel Nice, Section Lead for Research and Development at Exeter Clinical Laboratory (ECL), and Rebecca Smith, Gastroenterology Specialist Registrar, both from the Royal Devon University Healthcare NHS Foundation Trust, discussed several critical topics. This included the importance of optimising early treatment through precise drug monitoring, using TDM to adjust drug doses and prevent treatment issues, and the promising new technologies that are advancing point-of-care (POC) patient management. This blog highlights the key insights and takeaways from their presentations.

The changing landscape of IBD management

The global incidence of IBD continues to rise, creating significant health and economic challenges for communities around the world.¹ As a result, a large amount of research is being carried out to determine the most effective ways of managing these digestive diseases. One key topic under investigation is understanding the impact of immunogenicity on IBD treatment outcomes. Recently, the PANTS study² highlighted several risk factors for immunogenicity leading to primary non-response and LOR, such as obesity, smoking, and genetic markers like HLA-DQA1*05.

While some clinicians were hopeful that subcutaneous IFX might reduce the need for immunomodulators, emerging data suggests that this is not the case. On the face of it, IFX represents a significant development in IBD treatment, offering patients greater convenience and potentially higher drug levels with reduced peak and trough effects compared to intravenous (IV) administration. However, while the LIBERTY-UC and LIBERTY-CD studies^3-5 confirmed the efficacy of subcutaneous IFX for treating ulcerative colitis and Crohn’s disease, they also revealed high rates of immunogenicity – up to 65 % by the end of the first year – comparable to similar rates seen with IV treatment.

On top of this, the PROFILE study⁶ showed that early combined treatment – consisting of both a biologic and an immunosuppressant – can lead to better clinical outcomes for Crohn’s disease patients compared to a traditional step-up approach. Given these findings, managing immunogenicity remains crucial for effective therapy, and regular TDM and the use of immunomodulators are still often necessary to achieve remission.

TDM: current approaches and challenges

The main goal of TDM is to measure serum drug and ADA levels to determine whether patients are maintaining a therapeutic dose of anti-TNF medication, or experiencing an immunogenic reaction. Demand for serum drug and ADA tests has surged within the healthcare system, but critical questions remain: are we conducting the right tests at the right times, and do we fully understand the results?

Selecting an appropriate TDM strategy

A key challenge in TDM is selecting a testing strategy that maximises therapeutic effectiveness and therefore minimises the risk of LOR. TDM can either be used proactively to prevent subtherapeutic drug doses, or reactively, when patients are experiencing signs and symptoms of LOR. Although NHS Scotland offers both strategies through a central service, neither of these approaches are currently endorsed by the British Society of Gastroenterology (BSG) or the European Crohn’s and Colitis Organisation (ECCO). The OPTIMIZE IBD Trial,⁷ which finished recruiting earlier this year, could provide new evidence on optimal TDM use during the loading period of treatment that may inform national policy.

Interpreting test results

Once a TDM approach has been selected, the interpretation of different ADA assays presents an additional challenge. Drug-sensitive ELISAs only detect free antibodies when no drug is present, which is often too late for effective intervention. In contrast, drug-tolerant assays – which involve an acid dissociation step – can detect antibodies even when some drug remains in the serum, providing more timely information. The lack of consistency between assays can hinder comparisons between results from different laboratories. Fluctuating drug and antibody levels further complicate interpretation, requiring clinicians to discern whether variations are due to assay limitations or actual changes in patient immunogenicity.

The overall success of TDM depends on enhanced standardisation of testing and increased awareness of discrepancies between testing methods so that results can be correctly interpreted. In addition, innovative solutions like near-patient testing could improve the TDM service by allowing patients to perform drug and antibody level tests at home.

Personalised care: bringing TDM to the patient

Remote and decentralised testing could make TDM more accessible and convenient for patients, ensuring timely adjustments to treatment based on drug and antibody levels. This was demonstrated by the fingerPRICKS study⁸ during the COVID-19 pandemic. Capillary blood samples were found to be analytically equivalent to venous samples for ADM and IFX drug levels and ADAs, and remained stable in whole, uncentrifuged blood for up to seven days. The study also revealed that patients found home collection acceptable, and even preferable to repeated hospital visits for testing.

With this in mind, ECL has developed an end-to-end online solution for home blood collection, allowing clinicians to order blood tests to be sent directly to patients’ homes. Patients then send their samples to the lab, where BIOHIT’s IDKmonitor^® assays provide efficient assessment of circulating drug levels and total ADAs. This process grants patients access to accurate, reliable and efficient testing, while offering clinicians greater insights into treatment efficacy, enabling necessary dose adjustments based on results.

Future horizons in TDM

Besides home blood collection packs, there is a compelling case for POC devices that can be used by patients at home for self-testing or at infusion units prior to receiving treatment doses. This patient-centred approach not only stands to improve clinical outcomes, but also empowers patients to take a more active role in their care. As technology continues to advance, POC testing is set to become a cornerstone of IBD management, offering new levels of efficiency and ease.

Watch the full webinar to discover more about current IBD management and the bright future of TDM.

To find out more about BIOHIT’s IDKmonitor^® kits, visit: www.biohithealthcare.co.uk/products/therapeutic-drug-monitoring/

References

1. Alatab, S. et al. 2020. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: A systematic analysis for the global burden of disease study 2017. The Lancet Gastroenterology & Hepatology, 5(1):17-30. doi:10.1016/s2468-1253(19)30333-4.
2. Kennedy, N.A. et al.Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn’s disease: A prospective, Multicentre, cohort study. The Lancet Gastroenterology & Hepatology, 4(5):341-353. doi:10.1016/s2468-1253(19)30012-3.
3. Colombel, J.F. et al. DOP86 subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn’s disease: A phase 3, randomised, placebo-controlled study (Liberty-CD). Journal of Crohn’s and Colitis, 17(Supplement_1):i161-i162. doi:10.1093/ecco-jcc/jjac190.0126.
4. Colombel, J.F. et al. P874 impact of immunogenicity on clinical outcomes in patients with Crohn’s disease receiving maintenance treatment with subcutaneous infliximab: A post hoc analysis of the liberty-CD study. Journal of Crohn’s and Colitis, 18(Supplement_1):i1614-i1615. doi:10.1093/ecco-jcc/jjad212.1004.
5. Sands, B.E. et al. P492 subcutaneous infliximab (CT-P13 SC) as maintenance therapy for ulcerative colitis: A phase 3, randomized, placebo-controlled study: Results of the Liberty-UC Study. Journal of Crohn’s and Colitis, 17(Supplement_1):i623-i624. doi:10.1093/ecco-jcc/jjac190.0622.
6. Noor, N. et al. 2024. OP01 PROFILE: A multi-centre, randomised, open-label, biomarker-stratified clinical trial of treatment strategies for patients with newly-diagnosed Crohn’s disease. Journal of Crohn’s and Colitis, 18(Supplement_1):i1-i2. doi:10.1093/ecco-jcc/jjad212.0001.
7. Papamichael, K. et al. Proactive infliximab optimisation using a pharmacokinetic dashboard versus standard of care in patients with Crohn’s disease: Study protocol for a randomised, controlled, multicentre, open-label study (the OPTIMIZE trial). BMJ Open, 12(4). doi:10.1136/bmjopen-2021-057656.
8. Chee, D. et al. Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) for therapeutic drug monitoring in patients with inflammatory bowel disease. Journal of Crohn’s and Colitis, 16(2):190-198. doi:10.1093/ecco-jcc/jjab128.