Pediatric Crohn's Disease Activity Index Research Articles

Evaluation of exclusive enteral nutrition and corticosteroid induction treatment in new-onset moderate-to-severe luminal paediatric Crohn’s disease

To induce remission in luminal paediatric Crohn’s disease (CD), the ESPGHAN/ECCO guideline recommends treatment with exclusive enteral nutrition (EEN) or oral corticosteroids. In newly diagnosed moderate-to-severe paediatric CD patients, we determined the proportion of patients in which EEN or corticosteroids induced remission and maintained remission on azathioprine monotherapy. We included patients from the “TISKids” study assigned to the conventional treatment arm. Patients were aged 3–17 years and had new-onset, untreated luminal CD with weighted paediatric CD activity index (wPCDAI) > 40. Induction treatment consisted of EEN or oral corticosteroids; all received azathioprine maintenance treatment from start of treatment. The primary outcome of this study was endoscopic remission defined as a SES-CD score < 3 without treatment escalation at week 10. Secondary outcomes included proportion of patients without treatment escalation at week 52. In total, 27/47 patients received EEN and 20/47 corticosteroids. At baseline, patient demographics and several inflammation parameters were similar between the two treatment groups. At 10 weeks, clinical remission rates were 7/23 (30%) for EEN and 7/19 (37%) for corticosteroids (p = 0.661). Twenty-nine of 47 consented to endoscopy at 10 weeks, showing endoscopic remission rates without treatment escalation in 2/16 (13%) of EEN-treated patients and in 1/13 (8%) of corticosteroid-treated patients (p = 1.00). At week 52, 23/27 (85%) EEN-treated patients received treatment escalation (median 14 weeks) and 13/20 (65%) corticosteroid-treated patients (median 27 weeks), p = 0.070.Conclusion: In children with moderate-to-severe newly diagnosed CD, induction treatment with EEN or CS regularly is insufficient to achieve endoscopic remission without treatment escalation at week 10. Trial registration number: NCT02517684What is Known:• Endoscopic remission is associated with a low risk of disease progression.• FL-IFX was superior to conventional treatment in achieving and maintaining remission in paediatric patients with moderate-to-severe CD the first year from diagnosis.What is New:• In children with newly diagnosed moderate-to-severe CD, clinical remission rates and endoscopic remission rates without treatment escalation at week 10 were 30% and 13% after EEN and 37% and 8% after corticosteroid induction treatment.• The current treatment target was often not achieved by either EEN or corticosteroid induction treatment after bridging to azathioprine.

Overweight and Obese Status Is Not Associated With Disease Activity for Children and Adolescents With Newly Diagnosed Inflammatory Bowel Disease.

Despite the high prevalence of pediatric obesity, its impact on Crohn's disease (CD) and ulcerative colitis (UC) activity remains poorly characterized. The aim of this study was to evaluate disease-related outcomes in overweight and obese children with CD and UC. We conducted a retrospective cohort study using the ImproveCareNow Network, a multicenter registry of children with inflammatory bowel disease. We included children with newly diagnosed CD and UC enrolled in ImproveCareNow Network from September 2006 to December 2018 who had at least 1 follow-up visit 12-18 months after diagnosis. Patients were stratified into normal weight, overweight, or obese categories. Primary outcome was remission at 1 year based on physician's global assessment (PGA); key secondary outcomes included short pediatric CD activity index and pediatric UC activity index. There were 4,972 children included (70% CD). Compared with normal weight, obese and overweight children with CD did not have worse disease activity at 1 year based on PGA. However, obese children did have modestly worse disease activity based on short pediatric CD activity index (inactive 43% vs 58%, mild 48% vs 36%, and moderate-severe 9% vs 7% for obese vs normal weight, P < 0.01). For children with UC, there were no differences in disease activity at 1 year based on PGA or pediatric UC activity index. Logistic regression mirrored these findings. Obese and overweight children with newly diagnosed inflammatory bowel disease do not seem to have worsened disease activity at 1 year after diagnosis compared with normal weight children.

Food-Related Quality of Life in Children and Adolescents With Crohn's Disease.

Food-related quality of life (FRQoL) encompasses the psychosocial elements of eating and drinking. The FRQoL of children and adolescents with inflammatory bowel disease has not yet been assessed. This study aimed to evaluate the utility of the validated FR-Qol-29 instrument in children with Crohn's disease (CD). Children diagnosed with CD, a shared home environment healthy sibling, and healthy control subjects 6 to 17 years of age were recruited to this single-center, prospective, cross-sectional study. Children or their parent or guardian completed the FR-QoL-29 instrument. Internal consistency was assessed by completing Cronbach's α. Construct validity was established by correlating the CD FR-QoL-29 sum scores with the Physician Global Assessment and Pediatric Crohn Disease Activity Index scores. The discriminant validity was analyzed using a 1-way analysis of variance, and a Spearman's correlation coefficient test was completed to identify any correlations associated with FRQoL. Sixty children or their parent or guardian completed the FR-QoL-29 instrument (10 children in each subgroup). The internal consistency was excellent (Cronbach's α = 0.938). The mean FR-QoL-29 sum scores were 94.3±27.6 for CD, 107.6±20 for siblings, and 113.7±13.8 for control subjects (P = .005). Those with higher disease activity had worse FRQoL (Physician Global Assessment P = .021 and Pediatric Crohn Disease Activity Index P = .004). Inflammatory bowel disease FR-QoL-29 sum scores correlated with weight (P = .027), height (P = .035), body mass index (P = .023), and age (P = .015). FRQoL is impaired in children with CD. Healthy siblings also have poorer FRQoL than control subjects. Several clinical factors are associated with poorer FRQoL in children with CD including age and level of nutritional risk (weight, height, and body mass index). Further research is required validate these findings and to develop strategies for the prevention or treatment of impaired FRQoL in children with CD.

Extraintestinal manifestation of inflammatory bowel disease and associated factors in pediatric patients

ObjectiveExtraintestinal manifestations in irritable bowel disease (IBD), Crohn's disease and ulcerative colitis are reported in different system of the body. We aimed to investigate the factors determining disease severity and evaluate extraintestinal manifestations in patients with irritable bowel disease based on disease activity scoring system. MethodsThis cross-sectional study was conducted on all patients with irritable bowel disease referred to clinic and gastroenterology ward of (XXX). Medical history, gastrointestinal complications and incidence of extraintestinal manifestations were recorded. Disease severity in ulcerative colitis was rated based on PUCAI (Pediatric Ulcerative Colitis Activity Index) score and in Crohn's disease was calculated based on PCDAI (Pediatric Crohn's Disease Activity Index) score. ResultsOf 73 children included in our study, 54.80% were diagnosed with ulcerative colitis and 45.20% were diagnosed with Crohn's disease. The most prevalent symptom was weight loss (81.81%), diarrhea (72.72%) and abdominal pain (69.69%) in Crohn's diseases and bloody diarrhea (80%), abdominal pain (77.5%) and weight loss (57.5%) in ulcerative colitis. The average of PCDAI score was 43.44 and PUCAI score was 35.62. The most prevalent extraintestinal manifestation of the disease was arthritis in 7 Crohn's disease patients (21.21%) and 5 patients (12.5%) with ulcerative colitis, oral plague in 5 patients (15.15%) with Crohn's disease and erythema nodosum in 2 patients (6.06%) with Crohn's disease. ConclusionThe severity of oral plaque was positively associated with the severity of the disease. There was no significant association among other parameters. Scoring systems, to determine the extraintestinal manifestation, should be standardized based on the scoring outcomes.

Evaluation of Risk for Thromboembolic Events in Pediatric Inflammatory Bowel Disease.

The occurrence of thrombotic events in adult patients with inflammatory bowel disease (IBD) is linked to multiple interactions between hereditary and acquired risk factors. There are few published data concerning children with iBD. The aim of this study was to investigate the presence of thromboembolic risk factors also in children with iBD. We enrolled three groups of children: one with Crohn disease (cD), one with ulcerative colitis (Uc), and a control group of healthy subjects. For all the participants the potential thromboembolic risk was evaluated clinically and with laboratory tests. We studied: 30 children (25.6%) with CD, 28 (23.9%) with UC, and 59 (50.4%) healthy control subjects. Regarding Pediatric Crohn Disease Activity Index, no significant differences between thromboembolic risk factors and disease activity were detected. Instead, in the patients with UC, stratified with the Pediatric Ulcerative Colitis Activity Index, there was a statistically significant difference in serum fibrinogen levels between patients with mild and moderate/severe disease [3.8 (3.2-4.5) g/L vs 5.7 (4.8-6.2) g/L, P < 0.0032]. serum homocysteine levels were lower in healthy controls than in CD (P = 0.176) and UC (P = 0.026). An increased level ofhomocysteine in UC with a homozygous mutation in the methylene tetrahydrofolate reductase C677T gene was also observed. Our study showed that children with IBD have clinical features, acquired and congenital factors that can increase thrombotic risk, similarly to adults.

P511 Efficacy of Crohn’s Disease exclusion diet in different clinical scenarios in paediatrics; at onset of the disease and after loss of response to biological therapy

Abstract Background Crohn’s disease (CD) exclusion diet (CDED) associated with partial enteral nutrition (PEN) has showed to induce remission in different clinical scenarios of the disease. Our aim is to evaluate its efficacy at onset and after loss of response to biological treatment in paediatric CD. Methods Retrospective observational cohort study of children with CD treated with CDED+PEN. Demographic (gender, age at diagnosis and at CDED initiation), clinical (Paediatric Crohn’s Disease Activity Index (PCDAI) and weight Z score), and analytical (faecal calprotectin (FC), haemoglobin, albumin, C reactive protein (CRP), iron, ferritin, and erythrocyte sedimentation rate (ESR)) variables were analysed at 0, 6, 12, and 24 weeks of treatment. Primary outcome was clinical remission, defined as PCDAI &amp;lt;10 points. Results Fifteen patients were included (8 male); group A (n 9; mean age 15.8 years, [IQR:12.6–18.1]) received CDED+PEN at onset, while group B (n 6; mean age 12 years [IQR:10.7–15]) received it after loss of response to biologics. All patients in group A and 2 in B received azathioprine. In group B, 3 patients were on Adalimumab and 3 on Ustekinumab. Adherence at week 6 was 100% in both groups. Group A had a mean PCDAI of 15 [IQR: 11.25–17.5] at baseline and 100% of the patients achieved clinical remission by week 6 and maintained it through week 12; 87% (7/8) maintained clinical remission by week 24. One patient required step-up to Adalimumab due to sustained FC elevation. In group A PCDAI significantly improved at week 6 (p0.09), 12 (p0.002) and 24 (p0.006). FC and albumin also improved at week 6 (p0.02; p0.03), 12 (p0.016; p0.03) and 24 (p0.019; p0.016). ESR improved at weeks 12 (p0.021) and 24 (p0.027). Haemoglobin and iron only improved at week 24 (p0.048; p0.003). The weight Z score, CRP, and ferritin did not improve significantly in group A. In group B mean PCDAI at baseline was 20 [IQR: 3.75–39.38]; 100% achieved clinical remission at week 6 and maintained it at week 12. By week 24, 60% (3/5) maintained clinical remission (1 patient required steroids due to a relapse (moderate activity assessed by colonoscopy) and 1 patient presented with clinical relapse. PCDAI and FC decreased over time but did not reach statistical significance. The rest of variables did not show significant improvement in group B. Conclusion Treatment with CDED+PEN was well tolerated and patients had excellent adherence. Our cohort showed better results at disease onset than after loss of response to biologics. However, CDED+PEN is a new promising rescue strategy to treat CD after failure to previous biologics in a safe manner, and without needing to change the therapeutic target.

P099 Serum proteomic analysis reveals novel biomarkers associated with disease activity in pediatric patients with Crohn’s disease

Abstract Background Although Crohn’s disease (CD) is associated with a marked hyper-inflammatory response, identifying serum biomarkers associated with disease activity and outcomes is considered challenging, given lack of sensitivity of different assays. Our aim was to identify novel markers using Olink, a novel technology based on proximity extension assay, enabling detection of minute amounts of proteins. Methods Serum samples were obtained from pediatric patients with CD at the time of diagnosis and following induction therapy, and from control subjects, consisting of pediatric patients with normal endoscopic procedures, without past or present history of an immune-mediated disorder (e.g. celiac, diabetes). Serums were subjected to Olink (two panels used, consisting of 184 proteins), and analysis was performed on a Normalized Protein eXpression file by supervised, multivariate, principal component analysis and verification by univariate ANOVA with Benjamini-Hochberg and post-hoc Tukey analysis. Results Eighty-eight serum samples were collected: 30 from control subjects and 58 from 32 patients with CD (24 of them pre- and post-induction therapy). The median age of patients in the control and CD groups was 13.9 years (IQR 11.1–16.6) and 14.6 years (IQR 12.2–16.9), respectively (P=0.32). Twenty-four patients were treated with anti-TNFa agents and 8 with EEN. The median pediatric Crohn’s Disease Activity Index (PCDAI) decreased from 35 (22.5–42.5) to 5 (0–12.5, P&amp;lt;0.001) following induction therapy. We identified 72 proteins that significantly differed between patients and controls, and many of them were associated with CRP or ESR levels. String analysis identified several important nodes linking different proteins, including MMPs, MPO, EGFR and TNFRSF1A. Many proteins, such as resistin and different MMPs, showed a strong positive correlation with disease activity, based on PCDAI, while others, such as EGFR, showed a negative correlation. Several novel markers were identified to be highly expressed in the serum of patients with CD, including LRIG1, an intestinal stem cell marker, that was highly correlated with disease activity among the patients. Conclusion We identified novel serum markers that are associated with disease activity in pediatric patients with CD. These findings should be validated in future studies, and be complemented with expression and functional studies to define their role in mediating intestinal immune responses.

P186 Can transabdominal bowel ultrasound accurately detect both small and large bowel Crohn Disease in pediatric patients when compared to MRE?

Abstract Background Magnetic resonance enterography (MRE) has been the modality of choice to assess small bowel inflammation in patients with Crohn disease (CD). It can also assess large bowel when not feasible to assess endoscopically. Transabdominal bowel ultrasound (TABUS) is an attractive non-invasive tool to assess CD activity. Studies to date have focused on its correlation to large bowel endoscopic findings in adult CD. This study aimed to compare TABUS and MRE in identifying small and large bowel CD in pediatric patients. Methods Pediatric patients (≤18 years old) seen for suspected CD were prospectively enrolled and underwent baseline TABUS, endoscopy, MRE, blood work and stool studies. The Pediatric Crohn’s Disease Activity Index (PCDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD) were used to assess disease activity. Bowel wall thickness (BWT) was assessed by TABUS and MRE. TABUS measurements were scored with the Simple Ultrasound Activity Score for Crohn Disease (SUS-CD) (0=≤3mm, 1=3–4.9mm, 2=5–7.9mm, 3=≥8mm). Pearson Chi-square was used to compare BWT between TABUS and MRE. Results 21 patients (71% male) were included, with a median age of 13 years (range 6–16). Median PCDAI was 40 (25–49) and SES-CD 15 (6.5–22). There was a high level of agreement between MRE and TABUS (Figure 1) with some disagreement in the jejunum (n=9/21, 43%). For terminal ileal (TI) disease where there was disagreement, endoscopy of TI was in agreement with TABUS in two patients and MRE in five patients. Endoscopic TI disease that was documented as normal on TABUS was mild (SES-CD 3). In patients with abnormal MRE, BWT was not significantly different between the two modalities (Table 1). In patients with normal MRE, TABUS SUS-CD scores were accurately 0 in almost all segments (score 1 in TI) (Table 2). TABUS correctly identified no fistulae and 2 small bowel strictures (identified at endoscopy), but did not detect 1 intra-abdominal abscess and 4 large bowel strictures (only 1 stricture seen on endoscopy). Excessive lymph nodes (&amp;gt;4) were successfully seen on TABUS in 10/16 patients. TABUS correctly identified 75% of patients with significant mesenteric fibrofatty proliferation. Hyperemia on TABUS corresponded to an abnormal MRE for that segment in 92–100% of small bowel and 50–86% of large bowel. Conclusion TABUS and MRE are comparable modalities in the assessment of small and large bowel disease in newly diagnosed pediatric CD patients. Assessment of proximal small bowel is complex, and MRE may over-call disease. MRE still plays an important role in assessing abscesses and mild large bowel narrowing. Hyperemia on TABUS is an important indicator of active bowel inflammation, and is particularly useful for endoscopically inaccessible small bowel.

DOP67 First-line infliximab is cost-effective compared to conventional treatment in paediatric Crohn’s Disease – Results from the TISKids study

Abstract Background First-line infliximab (FL-IFX) induction treatment combined with azathioprine (AZA) is more effective to achieve clinical remission without treatment escalation at week 52 compared to conventional induction treatment (CONV) (Exclusive Enteral Nutrition or prednisone) combined with AZA in children with moderate-to-severe Crohn’s disease (CD). FL-IFX may lead to higher treatment costs compared to conventional treatment. However, data on cost-effectiveness of FL-IFX in children with CD is still limited. Therefore, our aim is to investigate the cost-effectiveness of FL-IFX in comparison with CONV. We hypothesized that cost effectiveness of FL-IFX is comparable to CONV in children with newly diagnosed moderate-to-severe CD in the first two years after treatment. Methods We included patients from the TISKids international randomized controlled trial in which children with moderate-to-severe CD were treated with either FL-IFX (Inflectra, biosimilar of IFX) or CONV.(1) Patients included outside of the Netherlands (n=6) or patients with serious comorbidity besides CD were excluded from this analysis (n=2). Data on healthcare consumption and costs were obtained per hospital for all included patients until week 104. Direct health-related costs were collected, including hospital visits, drug costs, laboratory tests, endoscopies and surgeries. The effectiveness of treatment was assessed by mean weighted paediatric CD activity index (wPCDAI) and faecal calprotectin (fcal) levels (µg/g) measured over time until week 104. This analysis was performed by a mixed model. Moreover, time to additional anti-tumor necrosis factor-α (anti-TNF) treatment up to 104 weeks after inclusion was assessed. Results In this analysis, 89 patients were included, 44 in the FL-IFX group and 45 in the conventional treatment group. There were no significant differences between the two groups at baseline. Interestingly, the mean costs were similar for FL-IFX (€34,783) and CONV (€34,923) after two years, p=0.97 (Figure 1). Mean fcal levels were lower for FL-IFX compared to CONV over two years (416 vs. 625, p=0.03). The mean wPCDAI scores over two years were numerically lower for FL-IFX compared to CONV (5.95 vs. 10.34, p=0.01), but this difference became smaller over time. Furthermore, the time to (re)start anti-TNF treatment was significantly longer in the FL-IFX group (median 68 weeks) compared to the conventional treatment group (median 32 weeks) (p=0.02) (Figure 2). Conclusion Treatment with FL-IFX is cost-effective compared to conventional treatment in the first two years after diagnosis in children with moderate-to-severe CD. Reference 1. Jongsma MME et al. Gut. 2020 Dec 31; DOI: 10.1136/gutjnl-2020–322339. / PMID: 33384335

P503 Early TNF-antagonist maintenance therapy results in better outcomes than immunomodulators in paediatric Crohn’s disease: A multi-centre prospective cohort study

Abstract Background Early initiation of TNF-antagonist (aTNF) therapy for Crohn’s disease (CD) is associated with greater clinical and endoscopic improvement but trialing an immunomodulator (IM) first remains common in paediatrics. This study aimed to determine if early aTNF is superior to IM maintenance therapy in paediatric luminal CD. Methods Children 2–17 years old with newly diagnosed CD were enrolled prospectively at one of 12 sites of the Canadian Children IBD Network. Patients with luminal inflammatory disease receiving IM or aTNF-based first maintenance therapy, following induction with steroids, exclusive enteral nutrition (EEN), or aTNF, were included. Those with perianal disease as the sole indication for aTNF were excluded. The primary outcome was sustained steroid-free clinical remission, defined by the short Pediatric CD Activity Index, at 6, 12, and 18 months, while continuing initial maintenance. A secondary outcome was combined sustained steroid-free clinical and endoscopic remission by 18 months, defined as the absence of ulcers at follow-up colonoscopy when ulcers were present at baseline. Multivariable logistic regression modeled the propensity of receiving aTNF maintenance therapy and 1:1 Greedy matching, without replacement, was used to match each of the participants who received aTNF with a participant who received an IM. The primary outcome was analyzed in the whole cohort, and in the subgroup receiving steroids or EEN as induction, using a Chi-square test, as well as in the matched group with a McNemar’s test, generalized estimating equation (GEE), and with a mixed model to account for clustering by centre. Sensitivity analyses with inverse probability treatment weights using GEE were performed. Results Among children with CD enrolled in the inception cohort study between 01/2014 and 12/2018, 464 met inclusion criteria and received IM (n=284) or aTNF (n=180 of whom 88 received steroids or EEN induction) as first maintenance therapy (Table 1). 162 patients were included in the matched cohort. In every analysis, more of the aTNF group achieved sustained 18-month steroid-free clinical remission, despite more severe baseline disease (Figure 1). The result remained significant in sensitivity analyses (Table 2). In patients with ulcers at baseline, 57.1% of the aTNF group versus 4.6% of the IM group achieved sustained steroid-free clinical remission and endoscopic remission by 18 months (p&amp;lt;0.001). Conclusion In this paediatric cohort, aTNF was superior to IM as first maintenance therapy. These results may help advocate for better access and funding for early aTNF therapy in paediatric CD.

Extraintestinal Manifestations in Children Diagnosed with Inflammatory Bowel Disease.

We aimed to evaluate the frequency of extraintestinal manifestations (EIM) in children with inflammatory bowel disease (IBD) and the correlation of EIM with disease activity index, disease type and disease age. Records of patients who were under the 18 years of age and followed up with the diagnosis of IBD were included in the study. The demographic characteristics of the patients, the age of the patients, the sex of the patients, the type of disease and the age of the disease were recorded. When patients were enrolled in the study disease activity indexes were calculated by examining the physical examination and laboratory values of the patients in their last visits, by using the Pediatric Ulcerative Colitis Activity Index (PUCAI) in Ulcerative Colitis (UC) and the Pediatric Crohn's Disease Activity Index (PCDAI) in Crohn's Disease (CD). It was conducted with a total of 44 patients, 40.9% (n=18) females and 59.1% (n=26) males diagnosed with IBD. The ages of the patients participating in the study ranged from 8 to 19 and the mean was found to be 14.64±3.19 years. According to the type of disease; 27.3% of the patients were CD and 72.7% were UC. When the disease activity is examined; 37.2% were in remission, 37.2% were mild, 16.3% moderate and 9.3% severe. The incidence of EIM in females is 77.8% and 65.4% in males. The incidence of EIM is 75% in CD and 68.8% in UC. Hepatobiliary involvement was detected in 41.5% (n=17) of the patients, joint involvement in 29.5% (n=13), osteopenia in bone in 16.3% (n=7), osteoporosis in 7% (n=3), ocular involvement (uveitis) in 2.3% (n=1) and skin involvement (erythema nodosum) in 2.3% (n=1). EIM are common in childhood IBD patients. It should be kept in mind that EIM are as common in UC as CD.

P072 Non-invasive Vagal Nerve Stimulation to Treat Crohn Disease and Ulcerative Colitis in Children and Young Adults: A Proof-of-Concept Clinical Trial.

Current inflammatory bowel disease (IBD) therapies are limited by incomplete efficacy, loss of response, side effects and high costs. Vagal nerve stimulation (VNS) is an investigational Bioelectronic Medicine therapy targeting the nervous system to treat IBD through an 'inflammatory reflex' that reduces systemic inflammation. Data in humans with IBD are promising but limited to two small studies using a cervically implanted VNS device in adults with Crohn disease (CD); no data exist to date using a non-invasive VNS modality in IBD. This study aimed to evaluate the efficacy and safety of transcutaneous auricular VNS (ta-VNS) in children and young adults with CD or ulcerative colitis (UC). IBD patients 10-21 years of age with mild/moderate CD or UC who did not achieve remission with conventional therapy, and a fecal calprotectin (FC) >200 ug/g within 4 weeks of study entry were enrolled. Subjects were randomized to receive either ta-VNS using a transcutaneous electrical nerve stimulator unit targeting the cymba conchae of the external left ear, or sham stimulation of the posterior lower leg, for 5 minutes once daily for a 2-week duration followed by a switch to the alternative stimulation for an additional 2 weeks. At week 4, all subjects were assigned to receive active ta-VNS for 5 minutes twice daily until week 16 so that all received 14 weeks of active ta-VNS by the end of the study. Primary study endpoint was defined as ∆FC ≥50% reduction from baseline to week 16. Secondary endpoints included improvement in weighted Pediatric Crohn Disease Activity Index (wPCDAI) or Pediatric Ulcerative Colitis Activity Index (PUCAI). Twenty-two subjects were enrolled (12 UC, 10 CD; median age 14.4 years [range 10-21] 54.5% male). Median baseline FC was 587 (range 18 - 3828, SD 1074). 5 subjects (4 UC, 1 CD) had FC levels 12.5 at baseline, 3 (50%) achieved clinical remission (wPCDAI ≤ 10) at week 16. In the full UC cohort (n = 12), baseline PUCAI ranged from 0-45. In the 6 with PUCAI > 10 at baseline, 2 (33%) achieved clinical remission at week 16. There were no safety concerns. Non-invasive ta-VNS reduced FC levels and improved symptoms in a pediatric cohort with mild/moderate IBD. Further research is needed to identify optimal electrical dose and settings to achieve peak anti-inflammatory effect and to identify the mechanistic principles for this therapy.

Long-Term Outcomes With Adalimumab Therapy in Pediatric Crohn Disease: Associations With Adalimumab Exposure.

Pediatric Crohn disease (CD) treatment goals have evolved. Among children receiving adalimumab (ADA) we examined long-term durability of clinical remission, linear growth, and associations of trough concentration (TC) with biomarker, endoscopic and imaging outcomes. Single-center retrospective study. Pediatric CD activity index, C-reactive protein, fecal calprotectin, and height measured longitudinally. Discontinuation due to secondary loss of response (LOR) was assessed using Cox proportional hazards model. Associations between TC and clinical and biomarker remission, endoscopic and magnetic resonance imaging (MRI) improvements were assessed using Cox regression with time-dependent covariates. Between January 2007 and June 2018, 213 children (median age 14.1 years (interquartile range [IQR] 12.5-15.7) 65% males) initiated ADA. One hundred and seventy-four (82%) achieved clinical remission (PCDAI < 10). During 24.8 (IQR 15.6-38.4) months follow-up, 26 (15%) discontinued ADA due to LOR, and 10 (6%) due to adverse events. Being anti-tumor necrosis factor (TNF) naïve and inflammatory behavior associated with increased likelihood of clinical remission (odds ratio [OR] 2.39, P = 0.033, and 3.13, P = 0.013, respectively) and with decreased LOR (hazard ratio [HR] 0.3, P = 0.002, and HR 0.35, P = 0.01, respectively). Cumulative LOR among 135 anti-TNF naïve patients: 0%, 8%, 15% within 1, 2, 3 years, similarly durable with mono- and immunomodulator combination therapy. Among pre-/early pubertal children mean height (-0.82) normalized to -0.07. TC consistently >7.5 ug/mL was associated with durable clinical remission (HR = 17.24, P < 0.001); TC >10 ug/mL with durable biomarker remission (HR = 6.56, P < 0.001) and endoscopic (OR 10.4, P = 0.002) and MRI (OR 7.6, P = 0.001) improvements. ADA monotherapy maintains durable clinical remission. Biomarker remission, mucosal and transmural improvements were associated with greater ADA exposure.

Induction of Remission in Pediatric Crohn's Disease Patients Assessed by the Mucosal Inflammation Noninvasive Index.

Mucosal healing (MH) is the main therapeutic goal of Crohn’s disease (CD). The Mucosal Inflammation Noninvasive Index (MINI) appears to be a promising tool for distinguishing MH from its inflammation. This study aims to evaluate MINI in monitoring remissions induced by exclusive enteral nutrition (EEN) in pediatric CD patients. Out of 55 newly diagnosed CD children, 31 who completed 6–8 weeks of EEN were analyzed. Clinical and biochemical data, activity of CD assessed with the Pediatric Crohn’s Disease Activity Index (PCDAI) and MINI were compared within seven days pre- and post-EEN. Response to induction therapy was defined as a decrease of PCDAI by >12.5 points. The follow-up was performed up to 12 months after EEN termination. Out of 31 children who completed 6–8 weeks of EEN, eight required corticosteroids in addition to EEN. Twenty-four patients (77%) responded to induction therapy. In responders, MINI decreased from 19 (Q1:17; Q3:22) to 12 (Q1:6; Q3:14), p < 0.001. The diagnostic accuracy of post-EEN MINI and post-EEN fecal calprotectin (FC) for treatment failure were AUC: 0.899 (95%CI: 0.737–1.000) and 0.762 (95%CI: 0.570–0.954), respectively. In the follow-up of 25 patients (80.6%), the post-EEN MINI of ≥13 points predicted CD relapse (87.5% sensitivity; 64.7% specificity), while FC had no prognostic value. MINI allows for monitoring of EEN and is superior in predicting disease relapse to FC.

The assessment of plasma fatty acid profiles in newly diagnosed treatment-naive paediatric Crohn's disease.

Fatty acid (FA) profiles as potentially relevant components of Crohn's disease (CD) have been insufficiently analysed. We sought to explore the plasma profiles of n-3 and n-6 polyunsa-turated fatty acids (PUFAs) in newly diagnosed untreated active CD. We included 26 consecutive CD pediatric patients (<19 years) and 14 healthy controls (HCs). Disease characteristics, including inflammatory markers, dietary histories, and the Pediatric Crohn's Disease Activity Index (PCDAI), were obtained. The profiles of plasma FAs in plasma lipid classes were analysed by gas chromatography with FID detection of methyl esters. The erythrocyte sedimentation rate, C-reactive protein level and fecal calprotectin level (all p<0.001) were significantly higher in CD patients than in HCs. Most changes were observed in plasma phospholipids (PLs), such as a higher content of n-3 and changes in n-6 long-chain PUFAs in the CD group. The CD group had a lower ratio of n-6/n-3 PUFAs in PLs (p<0.001) and triacylglycerols (TAGs) (p<0.01). Correlations of the FA content in plasma PLs with disease activity scores of CD were also observed, which were positive for the sum of monounsaturated fatty acids (MUFAs) as well as oleic acid (18:1n-9) (both p<0.05). The metabolism of PUFAs is significantly altered even in treatment-naive newly diagnosed active pediatric CD, and the content of major FAs in PLs correlates with disease activity and inflammatory markers, thus probably contributing to the still unclear early disease pathogenesis.

Analysis of Risk Factors and Nursing Intervention Measures Affecting Nutritional Status of Children with Crohn's Disease.

In recent years, the incidence of Crohn's disease (CD) in the Asia-Pacific region is gradually increasing, and the onset age is decreased at the same time. The relapse of illness and long course of disease easily lead to malnutrition, which will affect the treatment effect of the disease and even worsen the disease. Therefore, it is very important to find the risk factors affecting the nutritional status of children with CD and to carry out effective nursing intervention accordingly. In our study, a total of 180 children with CD who were admitted to our hospital from April 2017 to April 2020 were analyzed retrospectively. The multivariate analysis showed that Pediatric Crohn's Disease Activity Index (PCDAI), platelet (PLT), hemoglobin (HB), hematocrit (HCT), and albumin (ALB) were independent risk factors affecting the nutritional status of children with CD. The results of AUC showed that combined monitoring of the PCDAI score and the expression of PLT, HB, HCT, and ALB indexes was of great value to evaluate the nutritional status of children with CD. Finally, a series of nursing intervention measures were proposed based on these results. It provides a theoretical basis for improving the nutritional status of children with CD and promoting the clinical outcome.

Nailfold Capillaroscopy as a Biomarker in the Evaluation of Pediatric Inflammatory Bowel Disease.

BackgroundNoninvasive screening and disease monitoring are an unmet need in pediatric inflammatory bowel disease (IBD). Nailfold capillaroscopy (NFC) is a validated technique for microvascular surveillance in rheumatologic diseases. NFC uses magnified photography to examine nail bed capillaries called end row loops (ERL). We aimed to identify variations in NFC in pediatric IBD patients and their associations with disease activity.MethodsPediatric patients with Crohn’s disease (CD) or ulcerative colitis (UC) and healthy controls were recruited. NFC was performed on patients with newly diagnosed IBD prior to initiating therapy, patients with established IBD, and controls. ERLs were quantified along with a 3mm distance on 8 nailfolds. Serum biomarker levels of disease activity and symptoms activity indexes were correlated with average ERL density digits on both hands. Statistics were performed using chi-squared, ANOVA, and linear regression.ResultsFifty-one IBD patients and 16 controls were recruited. ERL density was significantly decreased in IBD (Control: 19.2 ERL/3mm vs UC: 15.6 ERL/3mm vs CD: 15.4 ERL/3mm; P < .0001). ERL density was lower in UC patients with lower albumin levels (P = .02, r2 = 0.29).The change in ERL density over time predicted the change in pediatric CD activity index among CD patients (P = .048, r2 = 0.58) with treatment.ConclusionsOur data demonstrate ERL density is reduced in IBD compared to controls. Lower albumin levels correlated with lower ERL density in UC. In newly diagnosed CD, ERL density increases over time as disease activity improves with therapy. NFC may be a feasible biomarker of disease activity and utilized for monitoring IBD.

Assessing disease activity using the pediatric Crohn's disease activity index: Can we use subjective or objective parameters alone?

BACKGROUNDThe pediatric Crohn’s disease activity index (PCDAI) is used as a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease. AIMTo examine which items on the PCDAI drive assessment of disease activity, and how subgroups of subjective and objective items reflect change in disease state over time.METHODSSelective raw data from three prospectively collected datasets were combined, including 703 children with full PCDAI data at baseline, at 3-mo (Q1, n = 670), and 1-year (Q4, n = 474). Change in individual PCDAI scores from baseline to Q1 and to Q4 were examined using the non-weighted PCDAI. RESULTSAbdominal pain, well-being, weight, and stooling had the highest change scores over time. Objective indicators including albumin, abdominal exam, and height velocity followed. Change scores for well-being and abdominal exam did not explain significant variance at Q1 but were significant predictors at Q4 (P < 0.001 and P < 0.05). Subjective and objective subgroups of items predicted less variance (18% and 22%) on total PCDAI scores at Q1 and Q4 compared to the full PCDAI, or a composite scale (both 32%) containing significant predictors. CONCLUSIONAlthough subjective items on the PCDAI change the most over time, the full PCDAI or a smaller composite of items including a combination of subjective and objective components classifies disease activity better than a subgroup of either subjective or objective items alone. Reliance on subjective or objective items as stand-alone proxies for disease activity measurement could result in misclassification of disease state.

Experience Using Ustekinumab in Pediatric Patients With Medically Refractory Crohn Disease.

Ustekinumab (UST), a human monoclonal antibody against interleukin-12 and 23, is approved to treat adult patients with psoriasis or Crohn disease (CD). Outcomes data for off-label use in pediatric patients with CD are limited. We conducted a retrospective cohort study to analyze the long-term efficacy of UST, including dose adjustments, in the treatment of pediatric patients with medically refractory CD. Adverse events were documented. We identified 40 pediatric patients with CD treated with UST between January 1, 2016 and December 31, 2019. Electronic medical records were reviewed for demographics, Paris Classification, significant comorbidities, previous CD therapy, adverse events after initiation, and surveillance markers at the time of their first dose and most recent clinic visit. A validated abbreviated pediatric CD activity index (aPCDAI) was used to assess response to therapy. Thirty-eight pediatric patients with CD, including 34.2% with stricturing or penetrating disease, were analyzed after initiation of treatment with UST. Median age at diagnosis of CD was 12.5 years, and median age at UST induction was 17.2 years. No patients were anti-TNF-naive, and 34.2% were previously exposed to 2 or more anti-TNF agents. At time of last follow-up, 84.2% of patients remained on UST for a median duration on UST of 62.1 weeks, and 60.5% achieved clinical remission. Patients had significant improvement in aPCDAI scores, clinical remission rates, albumin, and hematocrit, and 89.5% of patients had no significant adverse events. Similar results were observed among those who required dose adjustment, including 61.1% achieving clinical remission, and among those with perianal disease, including 38.5% achieving clinical remission. Our data suggest that, within our cohort of pediatric patients with CD, UST has long-term efficacy with no observed safety concerns. Dose adjustment may be helpful in achieving clinical remission.

Efficacy and safety of infliximab in the treatment of pediatirc Crohn's disease

Objective: To analyze the efficacy and safety of the biological agent infliximab (IFX) in the treatment of pediatric Crohn's disease. Methods: A total of 86 children with Crohn's disease who had received IFX in three hospitals (Ruijin Hospital, Ruijin Hospital North and Shanghai Children's Hospital) in Shanghai from January 2007 to December 2017 were included in this retrospective study. The efficacy of IFX was assessed by comparing clinical and laboratory data before and after IFX treatment. Student t test, Mann-Whitney U test or chi-square test were used to analyze the data of the two groups. Logistic reggression analysis were used to analyze the effects of variables such as age, clinical characteristics, disease behavior and combined medications on the efficacy and safety of IFX. Results: Among the 86 children with Crohn's disease in the study, 50 were males and 36 females. The IFX treatment was initiated at 12.0 (7.1, 13.6) years of age, and the follow-up period was 94.1 (47.8, 185.5) weeks. Efficacy analysis showed that in the induction remission phase, the clinical response rate was 97% (79/81) and the remission rate was 74% (60/81). In the maintenance remission phase, the clinical response rate was 75% (51/68) and the remission rate was 68% (46/68). After 34 weeks of treatment with IFX, pediatric Crohn's disease activity index (PCDAI) (5 (0, 10) vs. 36 (26, 45)), C-reactive protein (3 (1, 8) vs. 8 (3, 31) mg/L), erythrocyte sedimentation rate (10 (6, 10) vs. 35 (20, 50) mm/1 h), platelet ( (327±107)×109 vs. (438±159) ×109/L), albumin ((37±6) vs. (30±6) g/L), hemoglobin ((116±16) vs. (103±18) g/L), change of body weight (-0.5±1.2 vs. -1.0±0.9), anemia (29% (20/68) vs. 75% (51/68)), and perianal disease (13/21 vs. 0) were significantly improved (all P<0.05). By the end of 34 weeks of IFX treatment, 25% (17/68) of children experienced secondary loss of response to IFX. Logistic reggression analysis showed that PCDAI>30 was positively correlated with secondary loss of response (OR=3.823, 95%CI 1.015-15.328, P=0.048), and combined with azathioprine was conducive to maintaining efficacy of IFX (OR=0.440, 95%CI 0.106-1.033, P=0.044). The IFX-related adverse events included infusion reactions in 17% (15/86) and infections in 42% (36/86) of children. Analysis showed that age<6 years was a risk factor for infusion reactions (χ2=6.556, P=0.010), and combined use of steroids (χ2=5.230, P=0.022) may increase the incidence of infection. Conclusions: IFX is effective in the treatment of pediatric Crohn's disease with favorable safety. Reducing secondary loss of response to IFX is an urgent issue that need to be addressed. At the same time, it is necessary to pay close attention to the adverse events during IFX treatment.