Infliximab trough level combined with inflammatory biomarkers predict long-term endoscopic outcomes in Crohn's disease under infliximab therapy.

BACKGROUND: Infliximab trough level (ITL) severely affects therapeutic outcomes of Crohn's disease (CD) patients under infliximab (IFX). Recently, frontier research has focused on identifying ITL based on different therapeutic targets. Although previous studies have elaborated clinical value of ITL monitoring on short-term outcomes in CD patients during therapy, studies contraposing the predictive value of ITL on long-term endoscopic outcomes in CD patients are still scarce domestically and overseas. AIM: To explore the predictive value of ITL in combination with inflammatory biomarkers on long-term endoscopic outcomes in CD with clinical remission during IFX maintenance therapy. METHODS: CD patients with endoscopic remission under long-term IFX maintenance therapy in the First Affiliated Hospital of Zhejiang Chinese Medicine University from January 2012 to December 2020 were collected. ITL and inflammatory biomarkers were continuously monitored during the therapy. The Step I study was conducted from weeks 14 to 54 of IFX treatment. The Step II study was conducted from weeks 54 to 108 of IFX treatment. Endoscopic outcomes were defined as endoscopic activity (Crohn's disease endoscopic index of severity score > 2 points or Rutgeerts score > i1) and endoscopic remission (Crohn's disease endoscopic index of severity score ≤ 2 points or Rutgeerts ≤ i1). Endoscopic relapse free survival was defined as endoscopic remission at the beginning of the study stage and maintaining endoscopic remission during the study stage. RESULTS: At week 14, low ITL [odds ratio (OR) = 0.666, 95% confidence interval (CI): 0.514-0.862, P < 0.01] and high fecal calprotectin (FCP) level (OR = 1.002, 95%CI: 1.001-1.004, P < 0.01) increased the risk of endoscopic activity at week 54. At week 54, low ITL (OR = 0.466, 95%CI: 0.247-0.877, P < 0.01) and high C-reactive protein (CRP) level (OR = 1.590, 95%CI: 1.007-2.510, P < 0.01) increased the risk of endoscopic activity at week 108. At week 14, ITL ≤ 5.60 µg/mL [area under the curve (AUC) = 0.83, 95%CI: 0.73-0.90, P < 0.001] and FCP > 238 µg/g (AUC = 0.82, 95%CI: 0.72-0.89, P < 0.001) moderately predicted endoscopic activity at week 54. ITL ≤ 5.60 µg/mL in combination with FCP > 238 µg/g indicated 82.0% possibility of endoscopic activity. At week 54, ITL ≤ 2.10 µg/mL (AUC = 0.85, 95%CI: 0.72-0.93, P < 0.001) and CRP > 3.00 mg/L (AUC = 0.73, 95%CI: 0.60-0.84, P = 0.012) moderately predicted moderate endoscopic activity at week 108. ITL ≤ 2.10 µg/mL in combination with CRP > 3.00 mg/L indicated 100.0% possibility of endoscopic activity. From weeks 14 to 54 of IFX treatment, patients with ITL > 5.60 µg/mL had higher rate of endoscopic relapse free survival than those with ITL ≤ 5.60 µg/mL (95.83% vs 46.67%). From weeks 54 to 108 of IFX treatment, patients with ITL > 2.10 µg/mL had higher rate of endoscopic survival free relapsed rate than those with ITL ≤ 2.10 µg/mL (92.68% vs 30.77%). CONCLUSION: Combination of ITL, CRP, and FCP contribute to long-term endoscopic prognosis monitoring. During IFX maintenance treatment, low ITL, high CRP level, and high FCP level were independent risk factors of CD patients with clinical remission in adverse endoscopy outcomes within 1-year follow-up.

Predictive value of blood concentration of biologics on endoscopic inactivity in inflammatory bowel disease: A systematic review.

BACKGROUND: Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease (IBD) patients, complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics. AIM: To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations. METHODS: We searched PubMed/MEDLINE, Embase, and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction. RESULTS: A total of 23 articles with 30 clinical studies and 1939 IBD patients were included. The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6 µg/mL in IBD. Blood concentration of infliximab reaching 5.0-12.7 µg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease. Blood concentration of adalimumab reaching 7.2-16.2 µg/mL or more could predict mucosal healing in IBD. The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8 µg/mL in perianal fistulizing Crohn's disease. Blood concentration of vedolizumab surpassing 25.0 µg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9 µg/mL. CONCLUSION: Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies, whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.