Maarten Cozijnsen

19 Chapter 1 General introduction increased effectiveness is lacking in pediatric CD, based on adult CD literature it is likely that combination therapy is more effective, at the cost of increased risk of adverse effects. The current CD treatment guideline thus suggests to “allow concomitant AZA treatment in the first 6 months of IFX therapy and then consider stopping AZA, but individualization of the strategy is required based on prediction variables”. 8 Another method used to increase effectiveness is monitoring of therapeutic drug levels (TDM). Drug level measurements are typically timed preceding an infusion, resulting in trough levels. IFX trough levels are considered therapeutic when roughly between 3 and 7 μg/ml based on adult CD literature. 42–44 Whether TDM increases the effectiveness of IFX has not been tested in pediatric CD. A prospective RCT in adult IBD patients with stable response to maintenance IFX, demonstrated increased remission rates in patients with sub- therapeutic levels when doses were routinely screened and optimized. 45 It did however not increase 1 year remission rates—the primary efficacy endpoint. Thus, in adult CD patients, TDM hasn’t proven to overall increase the effectiveness of IFX. However, TDMmay be more beneficial for children than for adults, as the risk of sub-therapeutic IFX levels is higher in pediatrics. 46 Predicting treatment response Predicting patients’ chances to respond to available treatment options can improve overall treatment success by enabling physicians to directly choose the treatment option that offers the highest chance for response—also known as precision treatment. There are three different ways in which treatment outcome prediction can improve overall treatment success (Figure 3). Firstly, by predicting—before treatment initiation—which patients respond to anti-TNF treatment and do not respond to alternative treatment options. Since 80-90% of pediatric CD patients respond to anti-TNF antibodies, research should focus on predicting who does not respond to alternative treatment options, e.g. as steroids, EEN and immunomodulators, to limit the delay of effective treatment initiation. Unfortunately, there is only very limited data published on this matter. Two trials assessed predictive markers for steroid responsiveness in adult IBD patients. 474849 Thiopurines effectiveness can be predicted to some extent by measuring thiopurine S-methyltransferase (TPMT) enzyme activity and not commencing thiopurines in patients with extremely-low TPMT activity. 50 Some data on predicting MTX responsiveness is available in the field of adult rheumatology 51 , but not for IBD patients and neither is data available for predicting response to EEN. Thus, only very limited data is available on predicting responsiveness to the alternative non-biologic treatment options.