• Crohn’s disease
• Inflammatory bowel disease
• biomarker
• children
• fecal
• ulcerative colitis

• Humans
• Biomarkers
• Feces/chemistry
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/metabolism
• Crohn Disease/diagnosis
• Crohn Disease/metabolism
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/metabolism

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.

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.

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.

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%).

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.

• Infliximab trough level
• C-reactive protein
• Fecal calprotectin
• Crohn’s disease
• Clinical remission
• Long-term endoscopic outcomes

• Biomarkers/analysis
• Crohn Disease/diagnosis
• Crohn Disease/drug therapy
• Crohn Disease/metabolism
• Endoscopy, Gastrointestinal
• Gastrointestinal Agents/adverse effects
• Humans
• Infliximab/therapeutic use
• Leukocyte L1 Antigen Complex
• Recurrence
• Remission Induction

• Crohn’s disease
• Fecal biomarkers
• Fecal lactoferrin
• Fecal markers
• Inflammatory bowel diseases

Achieving mucosal healing in patients with inflammatory bowel disease is related to a higher incidence of sustained clinical remission and it translates to lower rates of hospitalisation and surgery. The assessment methods of disease activity and response to therapy are limited and mainly rely on colonoscopy. This meta-analysis reviews the effectiveness of using faecal calprotectin as a marker for mucosal healing in inflammatory bowel disease. Two meta-analyses were conducted in parallel. The analysis on the use of faecal calprotectin in monitoring mucosal healing in colonic Crohn’s disease is based on 16 publications (17 studies). The data set for diagnostic values of faecal calprotectin in ulcerative colitis is composed of 35 original publications (total 49 studies). The DOR for the use of faecal calprotectin in Crohn’s disease is estimated to be 11.20 and the area under the sROCis 0.829. In cases of ulcerative colitis, the DOR is 14.48, while the AUC sROC is 0.858. Heterogeneity of the studies was moderatetosubstantial. Collected data show overall good sensitivity and specificity of the faecal calprotectin test, as well as a good DOR. Thus, monitoring of mucosal healing with a non-invasive faecal calprotectin test may represent an attractive option for physicians and patients with inflammatory bowel disease.

• diagnostics
• faecal calprotectin
• inflammatory bowel disease
• meta-analysis
• mucosal healing

Mucosal healing (MH) has emerged as a key therapeutic target in inflammatory bowel disease (IBD), and achievement of this goal is documented by endoscopy with biopsy. However, colonoscopy is burdensome and invasive, and substitution with an accurate noninvasive biomarker is desirable.

To summarize published data regarding the performance of noninvasive biomarkers in assessing MH in IBD patients.

We conducted a systematic review of studies that reported the performance of biomarkers in diagnosing MH in patients with IBD. The main outcome measure was to review the diagnostic accuracy of serum and fecal markers that showed promising utility in assessing MH.

We screened 1301 articles, retrieved 46 manuscripts and included 23 articles for full-text analysis. The majority of the included manuscripts referred to fecal markers (12/23), followed by circulatory markers (8/23); only 3/23 of the included manuscripts investigated combined markers (serum and/or fecal markers). Fecal calprotectin (FC) was the most investigated fecal marker for assessing MH. In ulcerative colitis, for cutoff levels ranging between 58 mcg/g and 490 mcg/g, the sensitivity was 89.7%-100% and the specificity was 62%-93.3%. For Crohn’s disease, the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g (sensitivity 50%-95.9% and specificity 52.3%-100%). The best performance for a serum marker was observed for the endoscopic healing index, which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein.

Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization.

• Inflammatory bowel disease
• Ulcerative colitis
• Crohn’s disease
• Biomarkers
• Serum
• Fecal
• Mucosal healing

• Biomarkers
• Colitis, Ulcerative/diagnosis
• Feces
• Humans
• Inflammatory Bowel Diseases/diagnosis
• Leukocyte L1 Antigen Complex
• Reproducibility of Results
• Severity of Illness Index

• C-reactive protein
• Crohn’s disease activity index
• cytokines
• inflammatory bowel disease

• microbiome
• metabolome
• protease activity
• pentanoate
• valerate
• dialister

• Adolescent
• Biological Products/therapeutic use
• Biomarkers/analysis
• Child
• Child, Preschool
• Crohn Disease/drug therapy
• Crohn Disease/metabolism
• Crohn Disease/microbiology
• Crohn Disease/pathology
• Feces/chemistry
• Feces/microbiology
• Humans
• Inflammation/drug therapy
• Inflammation/metabolism
• Inflammation/microbiology
• Inflammation/pathology
• Intestinal Mucosa/microbiology
• Intestinal Mucosa/pathology
• Leukocyte L1 Antigen Complex/analysis
• Lysine/analysis
• Metabolome
• Peptide Hydrolases/metabolism
• Valerates/analysis
• Veillonellaceae/isolation & purification
• Wound Healing

• MR/P002536/1 Medical Research Council
• MR/P028225/1 Medical Research Council

BACKGROUND

The Crohn’s Disease Endoscopic Index of Severity (CDEIS) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) are two validated endoscopic scoring system to evaluate patients with inflammatory bowel diseases (IBD). We conducted this study to evaluate the correlation between clinical symptoms and lab tests with these indexes in patients with Crohn’s disease (CD) and ulcerative colitis (UC).

METHODS

In this analytical study, 373 consecutive patients referred to Shahid Mohammadi Hospital with IBD were enrolled. All patients underwent complete ileocolonoscopy, and the endoscopic severity indexes (CDEIS and UCEIS) were calculated, and their relation with clinical symptoms and lab tests was evaluated.

RESULTS

Fever observed only in six patients (1.6%). It was associated with significantly higher CDEIS and UCEIS (p = 0.02 and p < 0.001, respectively). Also, diarrhea was correlated with significantly higher UCEIS (p < 0.001). The mean fecal calprotectin was 647.64 ± 409.37 µg/g in CD and 567.30 ± 342.49 µg/g in UC patients. Higher calprotectin level was observed in patients with higher CRP level (p = 0.001), erythrocyte sedimentation rate (ESR) level, CDEIS, and UCEIS (r = 0.438; 0.473; and 0.517; respectively, all with p < 0.001).

CONCLUSION

Our study showed that although fever and diarrhea are associated with higher endoscopic severity scores in patients with IBD, no clinical symptom could reliably predict the endoscopic results, alone. Furthermore, higher fecal calprotectin level is associated with higher ESR and C reactive protein levels, CDEIS, and UCEIS.

• Crohn’s Disease Endoscopic Index of Severity
• Fecal calprotectin
• Inflammatory bowel diseases
• Ulcerative Colitis Endoscopic Index of Severity

• Crohn’s disease
• biomarker
• c-reactive protein
• endoscopy
• fecal calprotectin
• inflammatory bowel disease
• mucosal healing
• ulcerative colitis

• Capsule endoscopy
• Colonoscopy
• Crohn's disease
• Fecal calprotectin
• Fecal markers

• Adult
• C-Reactive Protein/analysis
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/psychology
• Crohn Disease/complications
• Crohn Disease/psychology
• Cross-Sectional Studies
• Female
• Health Surveys
• Humans
• Inflammatory Bowel Diseases/blood
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/psychology
• Male
• Outpatients/statistics & numerical data
• Prevalence
• Psychological Tests
• Quality of Life
• Spain/epidemiology
• Vitamin D/analogs & derivatives
• Vitamin D/blood
• Vitamin D Deficiency/blood
• Vitamin D Deficiency/epidemiology
• Vitamin D Deficiency/etiology
• Vitamin D Deficiency/psychology

Fecal calprotectin (fC) level is a predictive marker of mucosal healing for patients with inflammatory bowel disease (IBD). Home fC tests are now available. We evaluated the performance of the smartphone-based IBDoc home testing system in patients with IBD and obtained their feedback as an objective patient-reported outcome.

This prospective study enrolled consecutive patients with IBD in clinical remission. fC in the same stool sample was assessed by using both the laboratory test (Quantum Blue calprotectin test) and home test (IBDoc). The correlation between the 2 tests was analyzed using the Pearson method. In addition, the patients were asked to fill a questionnaire based on their experience.

Fifty-one patients with IBD (68 tests and 49 questionnaires) were included. The correlation between Quantum Blue test and IBDoc was good (r=0.776, P<0.0001). After the test, 56% patients found IBDoc easy to perform, and 96% were satisfied with it. Thirty-nine patients (80%) had a strong (>70%) probability to use it for future monitoring if the price was acceptable. By using 250 μg/g as the cutoff, the agreement between home test and laboratory results was 80%, and by using 600 μg/g as the cutoff, the agreement increased to 92%.

The correlation between the laboratory and home tests was good. Most patients found the home test to be feasible and easy to use and preferred it over laboratory test and endoscopy for monitoring. Therefore, the home test could be used as an objective patient-reported outcome.

• Colitis, ulcerative
• Crohn disease
• Fecal calprotectin

Fecal calprotectin (FC) has emerged as one of the most useful tools for clinical management of inflammatory bowel diseases (IBD). Many different methods of assessment have been developed and different cut-offs have been suggested for different clinical settings. We carried out a comprehensive literature review of the most relevant FC-related topics: the role of FC in discriminating between IBD and irritable bowel syndrome (IBS) and its use in managing IBD patients In patients with intestinal symptoms, due to the high negative predictive value a normal FC level reliably rules out active IBD. In IBD patients a correlation with both mucosal healing and histology was found, and there is increasing evidence that FC assessment can be helpful in monitoring disease activity and response to therapy as well as in predicting relapse, post-operative recurrence or pouchitis. Recently, its use in the context of a treat-to-target approach led to a better outcome than clinically-based therapy adjustment in patients with early Crohn’s disease. In conclusion, FC measurement represents a cheap, safe and reliable test, easy to perform and with a good reproducibility. The main concerns are still related to the choice of the optimal cut-off, both for differentiating IBD from IBS, and for the management of IBD patients.

• Fecal calprotectin
• Inflammatory bowel diseases
• Crohn’s disease
• Ulcerative colitis
• Irritable bowel syndrome

• Biomarkers/analysis
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/drug therapy
• Colon/diagnostic imaging
• Colon/pathology
• Colonoscopy
• Crohn Disease/diagnosis
• Crohn Disease/drug therapy
• Diagnosis, Differential
• Feces/chemistry
• Gastrointestinal Agents/therapeutic use
• Humans
• Intestinal Mucosa/diagnostic imaging
• Intestinal Mucosa/pathology
• Irritable Bowel Syndrome/diagnosis
• Leukocyte L1 Antigen Complex/analysis
• Predictive Value of Tests
• Recurrence
• Reproducibility of Results
• Severity of Illness Index
• Treatment Outcome

• Crohn’s disease
• IBD
• fecal markers
• ulcerative colitis