Gastroenterology


with minimal antibody response indicate that treatment can be maintained with dose adjustments as necessary. Reactive TDM can be extremely useful to


inform clinicians of the reason underlying LOR when a patient has active disease – such as inadequate dose, an exaggerated immune response, or an inappropriate mechanism of the selected drug – and has proven more cost effective than empirical dose optimisation for the anti-TNF drug infliximab.15-17


However,


preliminary data suggests that proactive TDM might be associated with better therapeutic outcomes than empirical dose optimisation and reactive TDM,20-27


promoting higher rates


of mucosal healing, preventing IBD-related surgeries and reducing unfavourable outcomes, including IBD-related hospitalisation and treatment failure.19,28


The barriers and benefits of proactive TDM Routinely measuring drug responses benefits both patients and medical professionals; it can increase patients’ confidence in, and adherence to, an administered biological treatment, while providing clinicians with the information required to form long-term individualised care plans for patients with chronic disease. Gastroenterologists working in the Northern Care Alliance outsource both proactive and reactive TDM measurements to national reference laboratories in Exeter and Birmingham, where enzyme linked immunosorbent assays (ELISAs) – such as BIOHIT HealthCare’s IDKmonitor assays – are used to analyse serum and plasma samples to assess circulating drug levels and free and total ADAs. The results provide clinicians with advanced knowledge of how patients with well- controlled or quiescent disease are responding to a particular type and dose of medication. This information can help clinicians to


optimise the use of a first line drug, and this can prolong remission and treatment longevity, prevent flare-ups and minimise time spent in hospital. It can also avoid reliance on a second line of treatment – often a subsequent, originator biologic – which is often far more expensive than the first line biosimilar, and less effective due to high attrition rates. For these reasons, proactive TDM may seem like the obvious choice for the effective management of IBD patients. However, there are a number of barriers that continue to limit its uptake, including the expense of ongoing analyses, a perceived lack of clinical guidance about its implementation, and the time lag to receive results from an external laboratory.18,29


Current and future TDM approaches The hesitance of many clinicians to put proactive TDM into practice is unsurprising in view of its relatively recent addition to the standard of care for IBD. Although most gastroenterologists have welcomed its use in a reactive setting, a lack of experience and knowledge of its benefits as a proactive measurement tool, as well as perceptions about cost, limit its pre-emptive use.18


monitoring are valuable tools to aid IBD therapy, maximising the effectiveness of biologics and enhancing patient outcomes.


References 1 Aslam, N. et al. 2022. A review of the therapeutic management of ulcerative colitis. Therap Adv Gastroenterol, 15. doi: 10.1177/17562848221138160.


2 Kumar, A. et al. 2022. A review of the


Significant research has been conducted to examine the benefits of proactive TDM, including studies demonstrating its cost effectiveness compared to empiric dose escalation. However, its wider implementation requires ongoing research and the rollout of more accessible analysis methods that make it easier and more time efficient to apply in practice. Diagnostic technologies are evolving and,


while traditional systems require patients to attend clinics for sample collection, the validation and use of point-of-care sample collection and testing will soon enable clinicians to monitor IBD patients remotely, reducing transportation costs and turnaround times. This could also improve patient care for those with active disease, allowing drug dosage optimisation based on real-time pharmacokinetics results rather than outdated data from previous weeks or months.28 Advancements in clinical decision aids, based on model-informed precision dosing (MIPD), are also likely, as population pharmacokinetic studies continue to identify parameters and sources of dosing variability that could be applied to quickly calculate required doses and treatment schedules on an individual basis.18,28


These imminent innovations – along


with growing knowledge about the benefits of proactive TDM practices, improved availability of assays, and wider dissemination of clinical guidance regarding the use of proactive treatment monitoring – are key to maximising the efficacy of TDM in a proactive setting. Used together, reactive and proactive disease


CSJ FREE Webinar!


The themes highlighted in this article will be explored further in a free webinar taking place on Thursday, 26 October 2023, at 11:00 AM - 12:00 PM BST. ‘Pre-emptive vs reactive therapeutic drug monitoring in IBD’ will bring together Jimmy Limdi – Consultant Gastroenterologist and Head of the Section for IBD at the Northern Care Alliance NHS Foundation Trust – and Christian Selinger – Consultant


Gastroenterologist at Leeds Teaching Hospitals NHS Trust – to discuss proactive versus reactive therapeutic drug monitoring (TDM) for IBD. The main discussion will be moderated by


The Clinical Services Journal, where the two speakers will deliberate the benefits and limitations of using proactive and reactive TDM, with details of their Trusts’ practices and case studies. To register, visit: https://tinyurl. com/58548fbp


About the author


Jimmy Limdi is a Consultant Gastroenterologist and Head of the Inflammatory Bowel Disease Section at Northern Care Alliance NHS Foundation Trust (NE Sector) and Professor of Clinical Gastroenterology at the Manchester Academic Health Sciences Centre, University of Manchester. He is also Hon. Professor at the Manchester Metropolitan University and Deputy Director of Research & Innovation at the Northern Care Alliance NHS Foundation Trust, Manchester. Jimmy qualified in 1993 and completed


postgraduate training in Internal Medicine and Gastroenterology in Yorkshire and Manchester, followed by a period of research at the ICMS, Barts and The London, and University College Hospitals, London and a Visiting Fellowship at Boston University and Harvard, Boston, US.


September 2023 I www.clinicalservicesjournal.com 51


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