Personalising IBD treatment for better patient outcomes
Dr Christian Selinger, a Consultant Gastroenterologist at Leeds Teaching Hospitals NHS Trust
The treatment of inflammatory bowel disease (IBD) has evolved significantly since the widespread introduction of biopharmaceuticals such as TNF-α inhibitors infliximab (IFX) and adalimumab (ADM). Up to 85 per cent of patients with IBD have a clinical response to these therapeutics, but many show drug-unresponsiveness or secondary loss of response (LOR), often because of the development of anti-drug antibodies (ADAs) that lower the drug trough levels in the bloodstream.1 Drug responsiveness is affected by numerous complex and interlinked factors, such as disease type and severity, patient age, and interactions with other therapies. This makes it extremely difficult to predict which medication and dosage will be the most effective for each individual, or whether a patient is likely to lose response at some point in the future. Lack of response to treatment therefore presents a considerable challenge to clinicians in determining the correct course of action, and cuts down on the already limited therapy options available.
Our previous blog, A proactive approach to take control of IBD, highlighted the potential of proactive therapeutic drug monitoring (TDM) for supporting clinical decision making and improving treatment efficacy. Here, Dr Christian Selinger, a consultant gastroenterologist at Leeds Teaching Hospitals NHS Trust, builds on this fascinating discussion and continues to strengthen the case for implementing proactive TDM.
A new weapon in the fight against IBD
TDM of trough levels and ADAs is emerging as a useful tool for detecting drug unresponsiveness, and is commonly performed reactively when a lack of clinical improvement or loss of disease control is observed. However, pioneering groups across the country are also now carrying out proactive TDM to gain insights into possible drug unresponsiveness before the appearance of symptoms. This allows doctors to change the dosage or therapeutic sooner, which may help to prevent future LOR and improve treatment success.
The gastrointestinal services at Leeds Teaching Hospitals NHS Trust are using the IDKmonitor® Infliximab Total Anti-drug ELISA from BIOHIT reactively to detect bound and free ADAs in the bloodstream as part of its TDM programme for IFX. However, the service provides follow-up appointments as standard at 12 and 52 weeks following the final IV infusion of IFX, which presents the team with the opportunity to draw blood samples for proactive TDM at the same time. Assay results are combined with a thorough clinical assessment, medical history, drug trough level and imaging, to form a complete picture of each patient’s clinical status, which informs clinicians as to the degree or future likelihood of LOR.
Small steps towards success
Gastroenterologists have found the highly sensitive, drug-tolerant IDKmonitor® assay to be particularly useful in identifying patients with low-titre ADAs, which supports both the proactive and reactive investigation of primary non-response and secondary LOR to IFX. Proactive use of the assay has enabled the detection of elevated ADA levels in IBD patients receiving IFX at an early phase, aiding clinicians in making treatment decisions, for example, forestalling LOR by introducing an immunomodulator or combination therapy, or simply increasing dosage to avoid undertreatment.
The service also sends samples to an external laboratory for analysis with the IDKmonitor® Adalimumab Total Anti-drug Antibody ELISA, and this enables reactive TDM to be performed for ADM when patients present with drug unresponsiveness or secondary LOR. The team has noticed the benefits of this type of analysis, and is optimistic that proactive monitoring of ADM may also be advantageous in personalising treatment for better patient outcomes. This TDM approach has allowed more effective disease control through therapy optimisation, leading to better long-term outcomes for IBD patients on IFX and ADA. It has also helped the hospital to reduce the unnecessary use of drugs and invasive repeat procedures, such as colonoscopies or sigmoidoscopies, potentially contributing to overall cost savings for the NHS in the long run.
Discovery is on the horizon
Hand in hand with these tentative advances in TDM, clinicians within the gastrointestinal service at the trust are also involved in research to help establish biomarkers that will reliably indicate the predicted efficacy of each therapeutic for different patient groups and guide doctors further in the decision-making process. While these studies hold great promise, conclusive results will not be available for several years, meaning that TDM is currently the primary method of tailoring IBD treatment with biotherapeutics. In addition, very little data exists internationally to suggest whether TDM would enhance the outcomes of patients on other care pathways, such as subcutaneously delivered IFX and other biologics such as vedolizumab and ustekinumab. These knowledge gaps highlight the need for clinicians in Leeds – and in other facilities – to invest adequate resources into the study, trial and implementation of both proactive and reactive TDM in the near future.
TDM is slowly gaining more attention, but its uptake has so far been low due to lack of evidence and time and financial pressures facing the healthcare system. Routine clinical practice for proactive TDM in particular remains poorly defined, and evidence supporting its use is not yet compelling enough to adopt this strategy routinely, although there is a desire to convince decision makers that widespread trials would be a worthwhile endeavour. TDM of biological IBD therapies remains a relatively underused tool, but this more personalised approach to treatment shows potential for improving patient outcomes and saving NHS resources in the long term. More studies are certainly needed to identify the advantages of both proactive and reactive TDM for a range of biopharmaceuticals, and this valuable data may finally attract the support needed to implement this promising technique in routine clinical practice throughout the UK.
To find out more about BIOHIT’s IDKmonitor® kits, visit:
www.biohithealthcare.co.uk/products/therapeutic-drug-monitoring/
References
- Selinger CP, Lenti M v., Clark T, et al. 2017. Infliximab Therapeutic Drug Monitoring Changes Clinical Decisions in a Virtual Biologics Clinic for Inflammatory Bowel Disease. Inflamm Bowel Dis. 23(12):2083-2088.
