Concerning drug levels monitoring any methodology is adequate. With respect to antidrug antibody levels, it will be necessary to define a gold standard method or to establish different cutoff levels for different methodologies.

Background Serum dipeptidyl peptidase 4 (DPP-4) has drawn particular interest as a biomarker in inflammatory bowel disease (IBD), as this protease inactivates several peptides that participate in the inflammatory cascade. Methods Two prospectively recruited cohorts consisting of 195 patients (101 had Crohn’s disease [CD] and 94 had ulcerative colitis [UC]) were evaluated using clinical indexes and followed up to assess for treatment escalation. Sixty-eight patients underwent endoscopic evaluation at baseline. In the second cohort of 46 biologically treated patients, treatment response was assessed. Serum DPP-4, C-reactive protein (CRP), and fecal calprotectin levels were quantified at baseline and during follow-up. Results Median DPP-4 levels were significantly lower in active IBD patients when compared with remitters (CD: 1043 [831–1412] vs 1589 [1255–1956] ng/mL; P < 0.001; UC: 1317 [1058–1718] vs 1798 [1329–2305] ng/mL; P = 0.001) and healthy controls (2175 [1875–3371] ng/mL). In fact, DPP-4 was able to distinguish clinical and endoscopic activity from remission, with areas under the curve (AUC) of 0.81/0.93 (CD) and 0.71/0.79 (UC), along with the need for treatment escalation, with comparable AUCs of 0.79 (CD) and 0.77 (UC). Furthermore, DPP-4 levels were higher in responders to treatment and more pronounced among UC (1467 [1301–1641] vs 1211 [1011–1448] ng/mL; P < 0.001) than CD patients (1385 [1185–1592] vs 1134 [975–1469] ng/mL; P = 0.015). Conclusions Our results suggest that serum DPP-4 can be used as a noninvasive biomarker of IBD activity and biological treatment response and a predictor of treatment escalation, particularly when combined with other biomarkers.

INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) is a membrane-bound glycoprotein that acts as a receptor but also exists in a soluble form. It has been recognized as a mediator of inflammation and considered a biomarker in inflammatory bowel disease (IBD). METHODS: We evaluated a prospectively recruited cohort, consisting of 101 patients with IBD, using validated clinical indexes; 22 patients with ulcerative colitis (UC) underwent endoscopic evaluation. Fecal DPP-4 (fDPP-4) levels were analyzed and correlated with clinical scores, Mayo endoscopic score (in UC patients), serum DPP-4, C-reactive protein, and fecal calprotectin. Immunohistochemical staining for DPP-4 in intestinal biopsies was also performed. RESULTS: When compared with remitters, median fDPP-4 levels were higher in patients with ileal Crohn's disease (CD) (7,584 [1,464–7,816] vs 2,104 [630–2,676] ng/mL, P = 0.015) and lower in patients with UC exhibiting clinical activity (1,213 [559–1,682] vs 7,814 [2,555–7,985] ng/mL, P < 0.001). Patients with UC presenting endoscopic activity also had lower levels than remitters (939 [559–1,420] vs 7,544 [4,531–7,940] ng/mL, P = 0.006). Fecal DPP-4 discriminated clinical activity from remission with areas under the curve of 0.76 (95% confidence interval [CI] 0.58–0.94, P = 0.015) and 0.80 (95% CI 0.68–0.93, P < 0.001) in CD and UC, respectively; it allowed to differentiate endoscopic activity in patients with UC, with areas under the curve of 0.84 (95% CI 0.63–1.00, P = 0.009). Immunohistochemical analysis revealed higher DPP-4 apical expression in UC remitters, but no statistically significant differences were revealed between patients with ileal CD. DISCUSSION: Our results suggest that fDPP-4 can be used as a biomarker of IBD activity, particularly in UC. The expression profiles in intestinal tissue might represent a functional compartmentalization of DPP-4 expression.

Background The roles dipeptidyl peptidase 4 (DPP4), aminopeptidase N (APN), and their substrates in autoimmune diseases are being increasingly recognized. However, their significance in inflammatory bowel diseases (IBD) is not entirely understood. This systematic review aims to discuss the pathophysiological processes related to these ectopeptidases while comparing findings from preclinical and clinical settings. Methods This review was conducted according to the PRISMA guidelines. We performed a literature search in PubMed, SCOPUS, and Web of Science to identify all reports from inception until February 2020. The search included validated animal models of intestinal inflammation and studies in IBD patients. Quality assessment was performed using SYRCLE’s risk of bias tool and CASP qualitative and cohort checklists. Results From the 45 included studies, 36 were performed in animal models and 12 in humans (3 reports included both). Overall, the methodological quality of preclinical studies was acceptable. In animal models, DPP4 and APN inhibition significantly improved intestinal inflammation.Glucagon-like peptide (GLP)-1 and GLP-2 analogs and GLP-2-relase-inducing drugs also showed significant benefits in recovery from inflammatory damage. A nonsignificant trend toward disease remission with the GLP-2 analog teduglutide was observed in the sole interventional human study. All human studies reported an inverse correlation between soluble DPP4/CD26 levels and disease severity, in accordance with the proposal of DPP4 as a biomarker for IBD. Conclusions The use of DPP4 inhibitors and analogs of its substrates has clear benefits in the treatment of experimentally induced intestinal inflammation. Further research is warranted to validate their potential diagnostic and therapeutic applications in IBD patients.