Gastroenterology
laboratory to specifically bind one of several molecular targets in the immune system.6 Many biological IBD medications – including infliximab, the most widely used biologic for both CD and UC – are directed at the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha), due to its role in the inflammation leading to digestive symptoms. TNF-alpha is found in the blood as part of the body’s normal response to infection but, in people with IBD, too much is produced, heightening immune responses and resulting in digestive tract irritation. Integrins and interleukins are also popular targets for biological therapies, as blocking these inflammatory mediators can reduce the symptoms of IBD and promote healing within the inflamed intestine.7
Biologics have
demonstrated clinical benefits for many IBD patients, but their availability and use have been limited largely because of their high costs. Instead, biosimilar medications – near identical copies of biologics containing the same active ingredient, mechanism of action and dosing – have been designed to increase the accessibility of IBD therapies and decrease treatment expense, while maintaining quality, safety and efficacy.8,9 An additional way to achieve a sustained
response to biologics and biosimilars is through combination therapy. Concomitant use of immunomodulators can allow increased systemic exposure to the administered drug by suppressing the formation of antibodies against it.10
The concurrent use of biosimilars
and immunomodulators is supported by both NICE11,12
and BSG13 guidelines. However, comorbidities, contraindications
or a strong objection from the patient against immunomodulatory agents, which can cause potential side-effects like nausea, increased risk of infections and malignancies, can all impact clinicians’ choices of IBD treatment.
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.
Person-centred therapy for a fluctuating disease Not every IBD patient responds to therapy in the same way and, although infliximab and other frequently used biologics are often effective at reducing inflammatory symptoms in IBD patients, individual responses can range from relatively rapid remission to a complete lack of improvement. Poor outcomes may result from subtherapeutic doses or the development of a humoral immune response, which can lead to the formation of antidrug antibodies (ADAs) and subsequent loss of drug efficacy. This is quite common; up to 30% of patients treated with anti- TNF drugs will fail to respond at all (primary non- response), while as many as half of the patients who do see an initial response will experience a reduction in the effectiveness of the drug over time (secondary LOR).14 The multitude of different treatment options
for IBD and the individuality of drug responses make it clear that a ‘one size fits all’ approach to treatment – although desirable – is not practical. Therefore, medical professionals within the Northern Care Alliance often rely on an initial, informed clinical decision of which biotherapeutic to use based on its immediacy of effect, as well as disease activity and severity – terms that describe the existing presentation and the long-term prognosis of the condition, respectively. Combining biosimilars
with a concomitant immunomodulator where possible can improve treatment effectiveness and reduce costs. Next, ongoing monitoring of treatment progress is a way to tailor therapy to the patient’s unique needs.
Persistent monitoring to improve outcomes In order to evaluate disease progression and drug responses, clinicians must collect and analyse information about a patient’s bloodstream drug levels and ADAs. TDM has emerged as a useful tool for optimising biological therapies – specifically anti-TNF therapy – in IBD and other immune-mediated inflammatory diseases (IMIDs). Reactive TDM is defined as the evaluation of drug concentrations and ADAs in the setting of primary non-response or secondary LOR to therapy. Proactive TDM utilises the regular measurement of drug trough concentrations and ADAs with dose adaptation to target an appropriate drug trough concentration. Reactive TDM has rationalised the management of primary non-response and secondary loss of response, and has proven more cost effective than empirical dose optimisation for the anti-TNF drug infliximab.15-17 Therefore, while 96.6% of gastroenterologists use TDM in reaction to LOR, only 54% use it as a proactive monitoring technique.18 A poor drug response is indicated by a
lack of improvement in symptoms, increased inflammatory biomarkers, or worsened status of the gastrointestinal tract. These factors are often monitored during treatment via clinical symptom scoring systems and biomarkers – like faecal calprotectin or serum CRP – as well as endoscopic, cross-sectional or ultrasound imaging. If a patient experiences a flare- up, or their symptoms or biomarkers fail to improve at predetermined time points during treatment – typically at week six and between week 12 and 14 – then the treatment plan should be re-evaluated. At this point, low drug levels and high antibody status may indicate a need to transition to another biologic or add immunosuppressants to the treatment regime.19
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Alternatively, moderate improvements
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