In parallel with drug monitoring disease monitoring through

In parallel with drug monitoring, disease monitoring through non-invasive biomarkers plays an important role in IBD patients, as it allows an assessment of the inflammatory burden without the risks involved in colonoscopy-related procedures. Calprotectin constitutes up to 60% of the cytosolic protein content in granulocytes, and its presence in Phenformin cost reflects the migration of neutrophils through the inflamed bowel wall to the mucosa (Gisbert and McNicholl, 2009). Recent evidences suggest that fecal calprotectin (FC) levels can be used to discriminate organic from functional disease, to assess disease activity and response to therapy, and to predict relapses (Benítez and García-Sánchez, 2015).
Material and Methods
Results
Discussion The values of IFX TLs, AUC and clearance reported in this study were within the range of those previously described in different studies and clinical trials (Fasanmade et al., 2009; Brandse et al., 2016; Paserchia, 1999; Anon, n.d.). Interestingly, the different IFX regimens had similar AUCs and clearance values, but could be distinguished based on their IFX TLs, which were significantly higher in the shorter regimen. Shortening the infusion interval is a commonly used strategy to intensify IFX therapy, shown to be superior or, at least, equivalent to the increase of IFX dosage in LOR (Katz et al., 2012; St Clair et al., 2002). As in the ATTRACT study, our results show that a shorter interval is associated with higher IFX TLs (St Clair et al., 2002). Moreover, this increase in IFX TLs - even without a concomitant increase in the IFX AUC - was sufficient for patients who suffered a LOR in the 8-weeks regimen regain response to IFX. In fact, their outcomes were similar to those experienced by the patients that remained in the 8-weeks\' regimen. The analysis of the cohort outcomes and disease indicators show that, despite being classified as in remission according to the Montreal classification, a considerable proportion of patients still has endoscopic lesions and a relatively high inflammatory burden. Interestingly, neither IFX TLs, AUC, clearance nor ATI concentrations were able to differentiate patients with positive and negative outcomes. IFX TLs are considered to be particularly useful for this: in fact, a search through the literature shows that IFX TLs are many times used to monitor kilocalorie drug on a therapeutic scenario, and different authors have found significant differences between IFX TLs in responders and non-responders, many times using cut-off values close to the one used in this study (3μg/mL), as described by Silva-Ferreira et al. and references included (Silva-Ferreira et al., 2016). Our analysis, however, suggest that these differences are absent or undiscernible when assessing clinically-stable and asymptomatic patients. We have then analyzed whether the pharmacokinetic profile of these patients could be used to evaluate their long-term risk of requiring therapeutic escalation. Interestingly, there was a clear and significant trend for patients with higher ATI levels to need therapeutic escalation later on their lives. Moreover, a cut-off of 3μg/mL could be statistically associated with the requirement of therapeutic escalation. These results concur with the data published previously by Edlund et al., who have shown that the presence of ATIs in Crohn\'s disease (CD) patients, irrespective of their concentration, eventually leads to a drop in IFX levels to values below a critically minimum concentration (Edlund et al., 2016). Moreover, Ungar et al. have shown that ATI development often precedes the onset of a clinical flare (Ungar et al., 2014). Additionally, a similar analysis including the FC levels has shown that values above 250μg/g are also significantly associated with the requirement of therapeutic escalation. Such a relationship has been suggested before by Burri et al., who claimed that changes of FC levels between measurements were related to therapeutic escalation (Burri et al., 2015). From a different angle but supporting the same core idea, Papamichael et al. have recently shown that the risk of relapse after IFX de-escalation in CD patients in composite deep remission is relatively low when FC levels are maintained within the normal range (Papamichael et al., 2016). Moreover, the results of a meta-analysis including six different studies suggest that FC is useful to predict relapses in quiescent UC and CD patients (Mao et al., 2012).