GASTROENTEROLOGY related complications. The advent of a subcutaneous
IFX formulation prompted some clinicians to anticipate a reduced need for immunomodulators in IBD treatment plans. On the face of it, this new formulation of IFX represented a significant therapeutic development, offering patients greater convenience of self-administration and potentially higher drug levels – with reduced peak and trough effects – compared to traditional intravenous (IV) administration.12 The LIBERTY-UC and LIBERTY-CD studies13-15
confirmed the efficacy of
The advent of point-of-care testing is one of the most promising developments in therapeutic drug monitoring, offering unprecedented accessibility and convenience for patients.
effective IBD management. Medications like IFX and ADM are cleared through several complex pathways, including proteolysis, loss through mucosal barriers during severe flare-ups, and binding to TNF-α molecules.7
anti-drug antibodies (ADAs) that can neutralise the therapeutic effect of the drug.9
This immune reaction In patients
experiencing high inflammation levels, substantial amounts of TNF-α inhibitors may be eliminated through these processes, requiring dose adjustments to maintain therapeutic levels. Moreover, treatment efficacy is closely linked to numerous patient-specific characteristics that can increase risk of immunogenicity.8
The individual nature of treatment responses The personalised anti-TNF therapy in Crohn’s disease study (PANTS)8
interferes with both pharmacokinetics and pharmacodynamics, and can lead to subtherapeutic drug trough levels, diminishing its effectiveness and either creating a vicious cycle of dose escalation to maintain desired therapeutic effects, or requiring a switch to an alternative therapeutic agent. Such dose increases not only raise the risk of adverse side effects, but also lead to higher treatment costs, and switching drugs may eventually exhaust available therapeutic options.
is
a UK-wide study that investigated treatment responses among IBD patients. The prospective observational study, published in The Lancet Gastroenterology & Hepatology, identified several factors linked to primary non-response or non-remission in patients receiving IFX and ADM. These include patient characteristics such as obesity and smoking, both of which are associated with a higher risk of subtherapeutic drug levels. Genetic markers – like the HLA- DQA1*05 allele – can also influence drug responses by predisposing some patients to heightened immune responses, further complicating treatment.
Immunogenicity: a key obstacle in effective treatment LOR often arises from an immunogenic response in which the body develops
34
Addressing LOR with combination therapy Step-up treatment approaches – where doses are gradually increased over time – are less frequently needed when biologics are combined with immunomodulators. Combination therapy has shown promise in mitigating immunogenicity, reducing the formation of ADAs and thereby decreasing the risk of LOR.10
The PANTS
study highlighted the potential of immunosuppressants to reduce ADA formation, enhancing the durability of treatment responses. Similarly, findings from the PROFILE study (predicting outcomes for Crohn’s disease using a molecular biomarker) showed that early combination treatment can lead to better clinical outcomes for Crohn’s disease compared to traditional dose escalations.11
subcutaneous IFX for treating ulcerative colitis and Crohn’s disease. However, these studies also revealed high rates of immunogenicity, with up to 65% of patients developing ADAs by the end of the first year – rates comparable to those observed with IV treatment. Therefore, combination therapy with immunomodulators remains essential for achieving sustained therapeutic benefits in IBD.
Optimising IBD treatment with TDM
Managing these complexities requires ongoing, tailored monitoring of each patient’s response to therapy. While combination therapy can be effective, it also brings potential side effects, such as nausea and increased susceptibility to infections and malignancies. Regular monitoring is essential to balance these risks, and this is where therapeutic drug monitoring (TDM) is playing a transformative role. TDM relies on the analysis of the levels of drug and ADAs circulating in a patient’s blood to determine whether or not an effective therapeutic dose of TNF-α inhibitors is being maintained, or an immunogenic reaction is occurring. Tracking these parameters provides data-driven insights into both treatment effectiveness and disease progression, allowing healthcare professionals to detect early signs of drug unresponsiveness. This provides them with an opportunity to reassess the treatment plan and, if necessary, consider alternative therapies before a patient’s condition worsens. Demand for drug and ADA testing in serum has surged within the healthcare system, but critical questions remain: are we performing the right tests at the right times, and do we fully understand the results?
This research highlights the
proactive advantages of combination therapies, particularly in high risk patients who might otherwise experience immune-
Choosing the right monitoring approach Up to 96.6% of gastroenterologists rely on TDM to guide treatment decisions when patients show an inadequate response to
MAY 2025
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