Gastroenterology
Therapeutic drug monitoring: a proactive approach
The pharmacological management of inflammatory bowel disease (IBD) has advanced dramatically in the last decade to include biological agents. However, many patients never respond to these therapies, and even more develop loss of response (LOR) over time. Therapeutic drug monitoring (TDM) is a valuable tool that aids clinical decision making, but there is some controversy over its pre-emptive use for monitoring disease progression. ProfessorJimmy Limdi discusses current approaches to TDM in clinical practice.
Inflammatory bowel disease (IBD) is a group of chronic, relapsing and remitting, progressive and potentially disabling immune-mediated conditions – comprising of ulcerative colitis (UC) and Crohn’s disease (CD) – causing chronic inflammation affecting the gastro-intestinal tract.1,2
In the UK, these conditions affect
approximately 300,000 people, a prevalence equating to 1 in every 210 individuals, with wide-reaching implications. Of this affected population, around 5,000 IBD patients fall under the care of the Northern Care Alliance NHS Foundation Trust, one of the largest IBD service providers in the country. The Trust consists of four hospitals and extensive community services within Bury, Rochdale, Salford and Oldham, and is considered a tertiary unit for IBD – attracting many complex referrals – as well as one of the top five centres for clinical trials in England.
Understanding intestinal inflammation The pathogenesis of IBD – chronic relapsing- remitting disorders involving inflammation of the small intestine, large intestine and/or colon – is not yet completely understood.3,4
Symptoms
of CD and UC range from pain and fatigue to diarrhoea and unintended weight loss but, while both conditions can present as relatively mild illnesses for some patients, they can be completely debilitating – with multi-dimensional and often negative effects on patients’ personal, psychological, professional and social wellbeing, and can lead to life-threatening complications in more severe cases. Researchers believe that IBD results from a combination of factors, including genetics, immunology, an imbalance of gut bacteria, and diet and lifestyle – which, when combined, lead to a compromised intestinal mucosa.
Genome-wide association studies (GWAS) have identified a number of genetic loci
associated with CD and UC, and variants at these sites may interfere with inflammatory pathways, enhancing susceptibility to intestinal damage.5
These genetic anomalies
may predispose individuals to IBD but, often, disease onset and perpetuation are largely influenced by environmental factors like smoking, diet, pathogenic infections and stress. Similarly, the intestinal microbiota, a system of microorganisms, bacteria, viruses, protozoa and fungi in a person’s digestive tract, also plays a role in health and disease within the gastrointestinal system. Add into the equation a dysregulated immune response, decreased immune regulatory mechanisms and defective barrier functions of the intestinal epithelium, and the luminal equilibrium can be disrupted, leading to uncontrolled intestinal inflammation.5
Treating inflammatory bowel disease Due to the heterogeneity of IBD mechanisms, no universal remedy exists, and patients should be treated on an individual basis depending on their signs and symptoms. The aim of most IBD treatments – including anti-inflammatory drugs, immunosuppressants and biomedicines – is to suppress inflammation and reduce the unpleasant effects of these long-term conditions.4 The advent of biological therapies at the
turn of this century – demonstrating efficacy in both induction and maintenance of remission, corticosteroid sparing effects, mucosal healing and reduction in hospitalisation and surgery – has redefined our perceptions around meaningful disease control. Biologics are complex proteins created in a
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