Value of ultrasound in the diagnosis of secondary loss of response in pediatric Crohn′s disease treated with Infliximab / 中华超声影像学杂志

Objective:To investigate the value of ultrasound in the diagnosis of secondary loss of response in children with Crohn′s disease at maintenance stage treated with Infliximab.Methods:From January 2017 to December 2021, 51 children with Crohn′s disease who received Infliximab treatment and clinical response in the Beijing Children′s Hospital Affiliated to Capital Medical University were retrospectively analyzed, and whether there was secondary loss of response during the maintenance period was observed. The ultrasound examination results at the 14th week of treatment were collected to understand the correlation between ultrasound examination of intestinal wall and peri-intestinal healing and secondary loss of response.Results:A total of 15 out of 51 patients (29.4%) experienced secondary loss of response during treatment follow-up up to 54 weeks. Compared to children with continuous response, children with secondary loss of response had a thicker intestinal wall at week 14 of treatment [5.0 (3.8, 6.0)mm compared to 3.0 (2.0, 4.0)mm, P<0.001], and a higher proportion of intestinal wall stratified structure disappearance [8/15 (53.33%) compared to 3/36 (8.33%), P<0.001]. When intestinal wall thickness>3.0 mm, the sensitivity was 0.955, and the specificity was 0.483. The sensitivity and specificity of clear diagnosis of secondary loss of response in intestinal wall stratification were 0.727 and 0.825, respectively. The sensitivity and specificity of combined diagnosis for secondary loss of response were 0.933 and 0.611, respectively. Conclusions:At the 14th week of treatment with Infliximab in children with Crohn′s disease, the thickness of intestinal wall measured by ultrasound being more than 3.0 mm and the disappearance of intestinal wall statified structure provide important information for the diagnosis of secondary loss of response.

Neutrophil-lymphocyte ratio at 14th week predicts loss of response to 52-week infliximab therapy in patients with Crohn's disease / 南方医科大学学报

OBJECTIVE@#Loss of response (LOR) has become an important clinical problem in patients with Crohn's disease receiving infliximab (IFX) treatment. Neutrophil-lymphocyte ratio (NLR) has been shown to correlate with the activity of inflammatory bowel disease (IBD), and NLR at the 14th week of IFX therapy potentially allows the prediction of sustained response to IFX in Crohn's patients. The aim of this study was to explore whether NLR at the 14th week of IFX therapy could predict the occurrence of LOR to IFX in Crohn's patients.@*METHODS@#Between January, 2012 and December, 2016, 54 patients with Crohn's disease underwent a 52-week treatment with IFX and successfully achieved response to the induction treatment in Zhongnan Hospital. We retrospectively examined their medical records and assessed the association between NLR at 14 weeks and LOR during IFX therapy.@*RESULTS@#Of the 54 patients, 15 (27.8%) showed LOR to IFX during the follow-up. We noted a significant increase in NLR at 14 weeks in the patients with LOR as compared with the patients with sustained response to IFX[3.51 (2.9-6.25) 1.77 (1.23-2.56), =0.00]. Receiver-operating characteristic analysis showed that at the cut-off value of 2.75, NLR at 14 weeks was predictive of LOR within 52 weeks of IFX therapy with a sensitivity of 93.33% and a specificity of 84.62%, and the area under curve (AUC) of NLR was 0.903 (0.731-0.959). Univariate analysis revealed a significant correlation between relapse-free survival and the NLR at 14 weeks (=0.00). Multivariate analysis identified NLR at 14 weeks as an independent prognostic factor for LOR with a hazard ratio of 1.851 (95% :1.096-3.026, =0.021).@*CONCLUSIONS@#NLR at the 14th week during IFX therapy is a useful predictor for LOR in patients with Crohn's disease.

Predictive value of the combination of infliximab trough levels and C reactive protein in secondary loss of response to infliximab after induced remission / 中华消化杂志

Objective To evaluate the role of infliximab trough levels(IFX-TL)and C reactive protein(CRP)concentration in prediction secondary loss of response(LOR)to infliximab(IFX)in patients with Crohn′s disease(CD)during IFX maintenance therapy since 14 weeks after induced treatment.Methods From November 2015 to October 2016,43 CD patients received IFX treatment were enrolled.IFX was initially given at zero,two,and six weeks at 5 mg/kg as induced therapy,and then the same dose was given every eight weeks as long-term maintenance treatment.Serum IFX-TL and CRP concentration were measured at 14thweek after the first IFX injection.The disease activity of CD was assessed by the Harvey-Braddshaw index.According to the follow-up results,the enrolled patients were divided into LOR group and continuous response group,and then the differences in IFX-TL and CRP concentrations at the 14thweek after induced therapy were compared between two groups.Mann-Whitney U test and receiver operating characteristic(ROC)curve were performed for statistical analysis.Results After a median 54 weeks of follow-up,18(41.9%)of 43 CD patients achieved a sustained response to IFX therapy,while 11 patients(25.6%)were LOR to IFX therapy.At the 14thweek after induced therapy,serum IFX-TL of LOR group was 2.30 μg/mL(0.52 μg/mL,2.92 μg/mL),which was lower than that of continuous response group(5.10 μg/mL(3.54 μg/mL,9.34 μg/mL)),and the difference was statistically significant(Z= -3.236,P=0.001).The CRP concentration of LOR group was 3.10 mg/L (0.38 mg/L,21.70 mg/L),which was higher than that of continuous response group(0.51 mg/L(0.27 mg/L, 1.50 mg/L)),and the difference was statistically significant(Z= -1.732,P=0.015).The results of ROC curve analysis indicated that at 14thweek after induced therapy the area under curve(AUC)value of predictive role of serum IFX-TL and CRP level in LOR to IFX was 0.864(95% confidence interval(CI)0.728 to 0.999),sensitivities were 83.3% and 81.8%,specificities were 94.4% and 54.5%,cut-off values of accuracies were 3.115 μg/mL and 5.93 mg/L.Conclusion IFX-TL<3.115 μg/mL and CRP concentration>5.93 mg/L at 14thweek since IFX induced therapy might be used as effective predictors of LOR in CD patients during maintenance therapy.

Trough level of infliximab is useful for assessing mucosal healing in Crohn's disease: a prospective cohort study

BACKGROUND/AIMS: Decreased trough levels of infliximab (TLI) and antibodies to infliximab (ATI) are associated with loss of response (LOR) in Crohn's disease. Two prospective studies were conducted to determine whether TLI or ATI better correlates with LOR (Study 1), and whether TLI could become a predictor of mucosal healing (MH) (Study 2). METHODS: Study 1 was conducted in 108 patients, including those with LOR and remission to compare ATI and TLI in discriminating the 2 conditions based on receiver operating characteristic (ROC) curve analyses. Study 2 involved 35 patients who were evaluated endoscopically. RESULTS: In Study 1, there were no differences between the 2 assays in ROC curve analyses; the TLI cutoff value for LOR was 2.6 µg/mL (sensitivity, 70.9%; specificity, 79.2%), and the ATI cutoff value was 4.9 µg/mL (sensitivity, 65.5%; specificity, 67.9%). The AUROC (area under the ROC curve) of TLI was greater than that of ATI. AUROC was useful for discriminating between the 2 conditions. In Study 2, the TLI was significantly higher in the colonic MH group than in the non-MH group (2.7 µg/mL vs. 0.5 µg/mL, P=0.032). CONCLUSIONS: TLI is better than ATI for clinically diagnosing LOR, and a correlation was observed between TLI and colonic MH.