20 Improving the therapeutic landscape of IBD with assessment of biomarkers and nutritional interventions Using biomarkers to monitor and select drug-based interventions The main treatment goals in the management of IBD are to induce and to maintain disease remission.57 Both in CD and UC, induction of remission is usually achieved with (intravenous) corticosteroids, often alongside or followed by the initiation of maintenance medications, which are principally targeting immune system components. Commonly prescribed drugs include 5-aminosalicylates, immunomodulators (including thiopurines, methotrexate or calcineurin inhibitors), and biological therapies (including TNF-α-antagonists such as infliximab [IFX], antiintegrins such as vedolizumab [VEDO] or anti-IL-12/23 inhibitors).2,3 Recently, a new class of maintenance drugs, referred to as the small molecules or JAK-STAT inhibitors, has been added to the therapeutic arsenal of IBD, of which the drugs tofacitinib and upadacitinib are good examples.58,59 For most of these medical treatments, particularly in the case of biologicals, it is challenging to determine which patients will benefit the most from which type of treatment. Unfortunately, due to the heterogeneity of the disease, the response rates for several types of these drugs are rather low. For example, up to 30-40% of patients demonstrate non-response or loss-of-response after induction therapy with TNF-α-antagonists, and up to 40-50% of patients show non-response or loss-of-response to VEDO induction therapy.60,61 Clinical factors have demonstrated poor predictive value with regard to treatment response, and there is a lack of accurate biomarkers that may be used to predict disease relapse and response to treatment.62,63 In clinical practice, it therefore remains challenging to predict which patients will respond to which specific treatment, underscoring the need for biomarkers to discriminate between future responders and non-responders against specific therapies. Furthermore, many of these treatments are intensive, unpredictable for patients, and expensive, which further emphasizes the importance of accurately predicting therapeutic responses. Another reason for improving response- and remission rates against medical treatments in IBD is the risk of surgical intervention in these patients. The majority of patients with IBD (CD: 70-90%, UC: 25-30%) eventually undergo intestinal resection during their disease course, mainly because they became refractory to the available medical treatments, or because of stricturing and/or penetrating disease complications or the development of colorectal cancer.64,65 Nutritional interventions Apart from developing novel medical treatments, there is growing interest in the field of lifestyle- and nutritional interventions in IBD. As for the latter, diet plays an important role in the development of IBD, and dietary intake patterns have appeared to be strongly associated with disease activity and the risk of disease relapse.66-68 In this context, a striking example is the effect of exclusive enteral nutrition (EEN) that has been demonstrated to induce disease remission in paediatric patients with CD.69 To make further progress in this field, it is of utmost importance to study both the effects of single food ingredients (e.g. vitamins or dietary fibres) and those of complete (anti-inflammatory) diets that are designed especially for IBD, i.e. diets that have the appropriate evidence-based properties in order to be potentially beneficial for patients with IBD. Single nutrients as nutritional therapeutic agents (neutraceuticals) require thorough assessment Chapter 1
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