Gastroenterology
reaction 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.
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
This research highlights
the proactive advantages of combination therapies, particularly in high risk patients who might otherwise experience immune-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 subcutaneous IFX for treating ulcerative colitis and Crohn’s disease. However, these studies also revealed high rates of immunogenicity, with up to 65 per cent 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?
Choosing the right monitoring approach Up to 96.6 per cent of gastroenterologists rely on TDM to guide treatment decisions when patients show an inadequate response to biologic therapies.16
This reactive tactic can help
clinicians to tailor therapy based on individual patient needs; low drug levels without antibodies may indicate a need for a higher treatment dose, while low drug levels with high ADA levels may direct clinicians to administer a different biologic or add immunosuppressants to the treatment regime.17
52
www.clinicalservicesjournal.com I March 2025
Sebastian Kaulitzki -
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Drazen -
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