Active Crohn's Disease Research Articles

P741 Characterisation of endoscopic improvements with risankizumab treatment in patients with moderately to severely active Crohn’s disease

Abstract Background Endoscopy is used to objectively evaluate disease severity in patients with Crohn’s disease (CD), and endoscopic remission is a target for disease control. Ulcer size is associated with longer-term endoscopic remission, so evaluating ulcers may inform longer-term outcomes. Risankizumab (RZB) is an interleukin 23p19 inhibitor approved for adults with moderately to severely active CD. In phase 3 trials, greater proportions of patients with CD achieved endoscopic outcomes including ulcer-free endoscopy with RZB induction and maintenance therapy vs placebo (PBO).1,2 We further investigated the effect of RZB on endoscopic outcomes by evaluating improvements in Simple Endoscopic Score for CD (SES-CD) components during these phase 3 trials. Methods This post hoc analysis used data from the phase 3 induction studies (ADVANCE [NCT03105128] and MOTIVATE [NCT03104413]) and phase 3 maintenance study (FORTIFY [NCT03105102]). Patients received intravenous (IV) doses of RZB (600 mg or 1200 mg) or PBO for 12 weeks, and clinical responders to IV RZB received RZB maintenance therapy (180 mg or 360 mg subcutaneously [SC]) or PBO (withdrawal) for 52 weeks. This analysis evaluated change in SES-CD subscores (size of ulcers, affected surface, and ulcerated surface) at induction week 12 and maintenance week 52 across ileocolonic segments (rectum, left colon, transverse colon, right colon, and ileum); analyses of improvement were based on a nonresponder imputation for patients with baseline subscores > 0 in the specific ileocolonic segment. Data from the induction studies were pooled for analysis; results for RZB 1200 mg IV induction are not reported. Shift data were from patients with available values. Results During the induction and maintenance studies, a numerically greater proportion of patients treated with RZB compared with PBO experienced improvements in any ileocolonic segment in SES-CD size of ulcers, ulcerated surface, and affected surface subscores (Figure). In general across each segment, a numerically greater proportion of patients treated with RZB induction and maintenance therapy compared with PBO experienced improvement from baseline SES-CD size of ulcer subscores of 2 or 3 (diameter 0.5–2 cm or diameter > 2 cm, respectively) to subscores of 0 or 1 (none or diameter 0.1–0.5 cm, respectively) at weeks 12 and 52 (Table). Similar patterns were observed for SES-CD ulcerated surface and affected surface subscores. Safety data for the phase 3 studies have been reported previously. Conclusion Patients treated with RZB experienced greater improvements in SES-CD components compared with PBO during the induction and maintenance studies.

P075 Early intestinal ultrasound non-response is a prediction tool of complicated disease outcome in Crohn’s disease patients treated with infliximab

Abstract Background The ultimate goal of Crohn’s disease (CD) treatment is to modify the natural course of disease and prevent complications. We aim to assess the role of intestinal ultrasound (IUS) as predictor tool for complicated disease. Methods Prospective longitudinal study including patients with active CD starting infliximab. Clinical, laboratorial and IUS parameters were assessed at week(W) 0, 14, 30, and 54. The IBUS-SAS score was used to assess ultrasonographic disease activity and includes, among others, bowel wall thickness (BWT) measurement. IUS response was defined as reduction in 25% in BWT and IUS remission as the normalization of BWT (≤3mm), doppler sign (≤1), stratification (BWS), and inflammatory fat in the most affected segment. Ileocolonoscopy was done at W0 and 54. Endoscopic healing (EH) was defined as SES-CD <3. We defined a composite outcome(CO) for complicated disease including development of stricturing or penetrating disease, need for bowel surgery, CD-related hospitalization, or the need to switching due to loss of response to therapy. Results We included 48 patients (48% male; median age 31 years, IQR 26-44). The median follow-up time was 23.5 months(M) (IQR11-38.25). The median time until the development of the outcome was 12M, IQR 9.75-15.25. During follow-up, 37.5% developed the CO (27.1% with stricturing or penetrating disease, 12,5% needed bowel surgery, 18,8% needed hospitalization and 6% switched therapy). Baseline disease behavior (B1:21,2% vs B2/B3:73.3% p<0.001) and a higher IBUS-SAS score (70.34 vs 58.80 p=0.042) were associated with development of CO during follow-up. Patients who developed the CO had a numerically higher BWT throughout the first year of therapy (W14: 5.00mm vs 3.65mm, p=0.007; W30: 4.78mm vs 3.43mm, p=0.007); a higher IBUS-SAS score was also seen at W14, W30 and W54 (57.00 vs 40.35, p= 0.03; 54.74 vs 31.00, p=0.004 and 29.84 vs 23.39, p=0.026, respectively). On survival analysis, IUS remission at W30 (HR 0.27 95% CI (0.76-0.94), p=0.04) and IUS response at W30 (HR 0.27 95% CI (0.09-0.94), p =0.015) were protective for the development of the CO. In multivariate Cox regression, the absence of IUS response at W30 (HR 4.80, 95% CI 1.03-22.45, p=0.046), and EH at W54 (HR 5.70, 95% CI 1.33-24.45, p=0.02) were independent predictors of worse outcome. The best cut-off at W30 to predict the CO was IBUS-SAS >52 (AUC 0.74) and BWT > 4.11 mm (AUC 0.75). Conclusion Early assessment of ultrasonographic response at W30 of therapy can help to predict prognosis in CD. Our results highlight that in the absence of significant IUS response after 6 months of therapy, we should consider treatment intensification and close monitoring to prevent complications.

CT energy spectral parameters of creeping fat in Crohn's disease and correlation with inflammatory activity.

Creeping fat is a kind of unique abnormal mesenteric tissue at the sites of diseased bowel of Crohn's disease. By using dual-energy CT enterography, this study aimed to evaluate the feasibility of spectral parameters in the quantitative analysis of mesenteric adipose tissue or creeping fat. In this study, patients with known or suspected Crohn's disease who underwent dual-energy CT enterography from March 1, 2019, to March 31, 2021, were enrolled. Among them, 40 patients with surgery and pathology-proven creeping fat were selected as the creeping fat Crohn's disease group, and 40 normal patients were selected as the control group. The quantitative spectral parameters including the slope of the Hounsfield unit curve, normalised fat-water concentration, normalised fat-iodine concentration, and normalised fat volume fraction at the enteric phases were obtained. Mann-Whitney U test, Kruskal-Wallis H test, and receiver operating characteristic curve analysis were applied to compare quantitative parameters among various groups. A significant difference was observed in the slope of the Hounsfield unit curve, normalised fat-water concentration, normalised fat-iodine concentration, and normalised fat volume fraction between mesenteric adipose tissue and creeping fat with Crohn's disease at the enteric phase (all p < 0.001). The slope of the Hounsfield unit curve of creeping fat at the enteric phase had a better capability to distinguish inactive and active Crohn's disease (AUC = 0.93, p < 0.001). Dual-energy CT enterography with quantitative spectral parameters is a potentially novel noninvasive tool for evaluating creeping fat in Crohn's disease. Energy spectral parameters of creeping fat in Crohn's disease are significantly different from normal mesenteric adipose tissues and are correlated with inflammatory activity. • Dual-energy CT enterography allows quantitatively assessing creeping fat with spectral parameters. • The creeping fat has distinct spectral parameters to normal mesenteric adipose. • The spectral parameters accurately differentiate active and inactive Crohn's disease.

Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease.

We comprehensively evaluated the expression of therapeutically targetable immune checkpoint molecules involved in celiac disease (CD). We have focused on the alteration of the CD200/CD200R pathway and Elafin expression in celiac disease and discussed their roles in regulating the immune response. There are limited data related to the expression or function of these molecules in celiac disease. This finding could significantly contribute to the understanding of the clinical manifestation of CD. CD200, CD200R and Elafin distributions were determined by ELISA and immunohistochemistry analyses in serum and biopsies of CD patients. Analyses of Th1 and Th17 cytokines were determined. PCR amplification of a fragment of the PI3 gene was carried out using genomic DNA isolated from whole blood samples of the study subjects. Different aliquots of the PCR reaction product were subjected to RFLP analysis for SNP genotyping and detection. We characterized the expression and function of the CD200-CD200R axis and PI3 in celiac disease. A significantly higher level of soluble CD200 and CD200R and lower expression of PI3 in serum of CD patients was observed compared to healthy controls. Consistent with our results, CD200 expression is regulated by IFN-gamma. Interaction of CD200/CD200R leads to production of type-Th1 and -Th17 cytokines. Regarding the PI3 genotype, the CT genotype proportion SNP rs1733103 and the GG genotype SNP rs41282752 were predominant in CD patients. SNP rs1733103 showed a significant association between the SNP variables and CD. In celiac disease the immune checkpoint is compromised or dysregulated, which can contribute to inflammation and the autoimmunity process. The study of these checkpoint points will lead to the development of targeted therapies aimed at restoring immunological balance in CD. Specific coding regions of the PI3 gene-splice variants predispose the Elafin protein, both at the transcriptional and post-translational levels, to modify its expression and function, resulting in reduced differential functional protein levels in patients with active celiac disease.

Upadacitinib (Rinvoq)

&#x0D; CADTH recommends that public drug plans reimburse Rinvoq for the treatment of moderately to severely active Crohn disease (CD) if certain conditions are met.&#x0D; Rinvoq should only be covered to treat adult patients with moderately to severely active CD who do not respond to, stop responding to, or who cannot tolerate conventional or biologic therapies, provided that Rinvoq is covered for a similar patient population and in a similar way to biologic therapies currently reimbursed by public drug plans for the treatment of adult patients with moderately to severely active CD.&#x0D; Rinvoq should only be reimbursed if prescribed by a physician experienced in the diagnosis and management of CD, if it is not used in combination with biologics for CD, and if the cost of Rinvoq is reduced so that it does not cost the drug programs more than the least costly biologic therapy reimbursed for the treatment of moderately to severely active CD. Patients must respond to treatment in the first 12 weeks of starting Rinvoq to continue receiving the drug.&#x0D;

Methanogenic Archaea in the Pediatric Inflammatory Bowel Disease in Relation to Disease Type and Activity.

The inflammatory bowel disease (IBD) is associated with gut microbiota dysbiosis; however, studies on methanogens-especially those focused on children-are extremely limited. The aim of this study was to determine the abundance of total methanogenic archaea and their three subgroups: Methanobrevibacter (Mb.) smithii, Methanosphaera (Ms.) stadtmanae, and Methanomassiliicoccales, in the feces of children with both active and inactive Crohn's disease (CD) and ulcerative colitis (UC). The results of a quantitative real-time PCR were cross-referenced with the disease type (CD vs. UC) and activity assessed with the use of Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI) indices, and fecal calprotectin (FCP) concentration, and compared with controls. There was a significant decrease in the number of total methanogens in CD and UC compared to controls. The prevalence of total methanogens was also lower in UC compared to controls. Furthermore, patients from the inactive UC group were colonized by a lower number of Mb. smithii, and demonstrated the most pronounced positive correlation between the number of Ms. stadtmanae and the FCP concentration. Our results demonstrate that gut methanogens are related to the type and activity of pediatric IBD.

Prospective study of an adalimumab combined with partial enteral nutrition in the induction period of Crohn’s disease

BackgroundAdalimumab monotherapy can suppress gut inflammation and induce remission in active Crohn’s disease but has some limitations. Exclusive enteral nutrition (EEN) is recommended for patients with mild to moderate Crohn’s disease (CD), but implementation is challenging.AimTo evaluate the effectiveness of adalimumab combined with partial enteral nutrition (PEN) in the induction therapy for Crohn’s disease.MethodsA prospective cohort study was designed and a total of 56 patients with active CD who met the criteria for enteral nutrition (EN) treatment in our hospital were selected. The baseline data of all patients were collected including age, sex and other general information. The changes in fecal calprotectin, C-reactive protein (CRP), albumin(Alb), hemoglobin (Hb), platelets (Plt), erythrocyte sedimentation rate (ESR), Crohn’s disease activity index score (CDAI), simple endoscopic score (SES-CD) and body mass index (BMI) were compared between the adalimumab combined with enteral nutrition (ADA+EN) group (N = 37) the adalimumab group (ADA) (N = 19) at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated. Then the ADA+EN group was divided into an adalimumab combined with exclusive enteral nutrition subgroup (ADA+EEN) and an adalimumab combined with partial nutrition subgroup (ADA+PEN) according to enteral nutrition intake. The changes in fecal calprotectin, CRP, Alb, Hb, Plt, ESR and CDAI, SES-CD and BMI were compared between the ADA+EEN group and the ADA+PEN group at week 0 (W0) and treatment outcomes at week 12(W12). The differences between the two groups before and after treatment were evaluated. To evaluate the effectiveness of the two treatments on patients’ quality of life, nutritional recovery and body composition, patients in the ADA+EN group were needed to complete the Inflammatory Bowel Disease Questionnaire (IBDQ), EQ-5D-5L, the EuroQol visual analogue scale (EQ-VAS) and body composition analysis.A total of 28 patients completed all questionnaires and body composition analyses at week 0 and week 12, including 10 patients in the ADA+EEN group and 18 patients in the ADA+PEN group, respectively. The differences of in IBDQ, EQ-5D-5L and body composition analysis were compared between the two groups at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated.ResultsThese investigated indexes such as calprotectin, Hb, Plt, ESR, Alb, BMI, CRP, CDAI and SES-CD scores were significantly different before and after treatment in the ADA+EN group (p < 0.01). However, fecal calprotectin, Hb, SES-CD scores and Alb in the ADA group were not statistically significantly different from W0 to W12 (p > 0.05). The fecal calprotectin and CDAI scores in the ADA+EN group were significantly lower than those in the ADA group after treatment. The differences in all factors before and after treatment between the ADA+PEN group and the ADA+EEN group were statistically significant (p < 0.05). However, there was no significant difference between the two groups at week 12 (p > 0.05).ConclusionAdalimumab combined with EN are more effective than ADA monotherapy in terms of endoscopy and clinical remission. By comparing the investigated indicators such as calprotectin, Hb, Plt, ESR ,CRP and SES-CD scores, it was proven that adalimumab combined with partial enteral nutrition or exclusive enteral nutrition has the same remission effect in induced Crohn’s disease. The combination of biological agents and partial nutrition can improve medical order compliance, psychological burden and quality of life. Therefore, adalimumab combined with partial nutrition can be used as the first-line treatment for CD induced remission.

The Spectrum of Magnetic Resonance Enterography Findings and the Role of Diffusion-Weighted Imaging in Patients with Active Crohn's Disease.

The goal of this study was to evaluate magnetic resonance enterography (MRE) findings and assess the role of diffusion-weighted imaging (DWI) in patients suffering from active Crohn's disease. This retrospective study included a total number of 76 patients diagnosed with active Crohn's disease, as established by the Crohn's Disease Activity Index (CDAI). The study consisted of 30 women and 46 men, ranging in age from 13 to 72 years. All participants underwent MRE with DWI sequences. The study was conducted at Imam Khomeini hospital in Tehran between 2013 and 2018. The imaging modality utilized for the study included a 3-T SIGNA Excite MRE machine and a Siemens Magnetom 3-T magnetic resonance imaging (MRI) machine. Bowel wall restriction was observed in less than half of the patients, and no significant correlation was found with extramural findings such as mesenteric edema. The study did not reveal any meaningful association between diffusion restriction and specific mural enhancement patterns, mesenteric lymphadenopathy with or without enhancement, or the length of the affected segments (P>0.05). The most common findings observed in MRI were ileum thickness in 72.4% of patients, mesenteric lymphadenopathy without enhancement in 46.1%, ileocecal thickness in 42.1%, DWI findings in 42.1%, the presence of a comb sign in 36.8%, and jejunum thickness in 30.3% of patients. MRE findings are useful in the evaluation of Crohn's disease activity.

Development and validation of a novel therapeutic drug monitoring-based nomogram for prediction of primary endoscopic response to anti-TNF therapy in active Crohn's disease.

Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn's disease (CD). However, the predictive role of therapeutic drug monitoring (TDM) of serum anti-TNF in monitoring the treatment of inflammatory bowel disease (IBD) remains controversial. To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram. Cross-sectional study. The simplified endoscopic activity score for CD (SES-CD), Crohn's disease activity index (CDAI), laboratory parameters, and the serum trough levels of IFX and ADA were assessed. The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort (p < 0.001). The IFX and ADA levels showed a weak but significantly negative correlation with SES-CD (p < 0.001), CDAI (p < 0.001), and C-reactive protein (CRP) (p < 0.001) at week 14 post-IFX therapy in the development cohort. Furthermore, the receiver operating characteristic curve revealed that an optimal level of IFX (4.80 μg/mL) and ADA (8.80 μg/mL) exhibited the best performance in predicting endoscopic response. Concomitantly, we developed a novel nomogram prediction model based on the results of multivariate logistic regression analysis, which consisted of CRP, albumin (Alb), and anti-TNF trough levels at week 14. The nomogram showed significant discrimination and calibration for both IFX and ADA in the development cohort and performed well in the external validation cohort. This study demonstrates a robust association between serum concentrations of IFX, ADA, Alb, and CRP and primary endoscopic response in active CD patients. Importantly, the TDM- and laboratory marker-based nomogram may be used to evaluate the primary endoscopic response to anti-TNF therapy, especially for optimizing treatment strategies and switching therapy in CD patients.

The synergy of dual faecal immunochemical and faecal calprotectin testing for accurate assessment of endoscopic and histological activity in inflammatory bowel disease.

Faecal biomarkers are increasingly utilized for disease assessment in inflammatory bowel disease (IBD). To characterize the relative and combined accuracy of faecal calprotectin (FC) and faecal immunochemical testing (FIT) for detecting endoscopic and histologically active disease in Crohn's disease (CD) and ulcerative colitis (UC), subdivided by disease location. A prospective cohort study. Patients with confirmed IBD undergoing routine ileocolonoscopy for activity assessment were prospectively recruited and performed both FC and FIT ±30 days of ileocolonoscopy. Endoscopic activity was assessed via the simplified endoscopic score for CD, Mayo endoscopic score for UC and histological activity graded as nil/mild/moderate. Receiver-operator curve analyses were utilized to assess the performance of FC and FIT per disease subtype and location. In all, 137 (79 CD, 57 UC) patients were recruited. FC was more sensitive than FIT in detecting active endoscopic (CD: 91% versus 69%, UC: 94% versus 82%) and histological (CD: 86% versus 55%, UC 88% versus 56%) disease. However, FIT was more specific than FC in detecting active endoscopic (CD: 94% versus 56%, UC: 85% versus 69%) and histological (CD: 93% versus 55%, UC: 96% versus 70%) diseases. FIT was more sensitive and specific than FC in detecting active colonic CD (endoscopic activity: 94% versus 93%, histological activity: 92% versus 77%, respectively); however, it was poorly sensitive for active ileal CD (43% versus 89%). FC demonstrated higher sensitivity and FIT higher specificity for active IBD. Hence, dual testing was synergistic, displaying excellent performance characteristics across most IBD locations and subtypes, holding promise for future clinical application. Not applicable.

Multimodal dynamic ultrasound approach as predictor of response in patients with Crohn's disease treated with ustekinumab.

The approval of ustekinumab (UST) has opened new options for the treatment of Crohn's disease (CD), but potential markers predicting the efficacy of this interleukin-12/23 inhibitor are lacking. Contrast-enhanced ultrasound (CEUS) is non-invasive alternative to endoscopy, demonstrating early transmural changes after treatment induction. We conducted a prospective monocentric study aiming to explore the value of multimodal intestinal ultrasound (IUS) in predicting the response to UST in patients with active CD who have been previously exposed to anti-tumour necrosis factor α (TNFα). Consecutive patients with moderate-to-severe CD involving the terminal ileum who were scheduled to begin UST therapy were enrolled between January 2020 and October 2021 in the inflammatory bowel diseases outpatient centre. A complete IUS evaluation, including B-mode, Doppler, dynamic CEUS and elastography, was performed at the time of induction (T0) and after 8 (T1), 16 (T2), 24 (T3) and 48 (T4) weeks of therapy. Each IUS parameter and their variations from baseline were correlated with endoscopic response and mucosal healing after 1 year. A total of 52 patients were included, 29 (55.8%) of which reached endoscopic response at T4. The univariate analysis revealed that, between T3 and T0, the percentage changes of bowel wall thickness, Limberg score, mean signal intensity, rise time, wash-in rate, C reactive protein and Harvey-Bradshaw Index were associated with long-term therapeutic outcome. Based on the above parameters, we developed an IUS score that showed a good performance in predicting 1 year-endoscopic response (area under the curve: 0.91). Multimodal ultrasound could be helpful to predict long-term therapeutic outcome in patients with CD treated with UST. NCT05987501.

Monocyte CD36 Expression Predicts Disease Activity in Patients With Crohn's Disease.

Background: Crohn's disease (CD) is a chronic intestinal inflammatory disease associated with genetic, environmental, and other unknown factors. Cluster of differentiation 36 (CD36) plays an important role in cancer, inflammation, and metabolic diseases. Although CD36 has recently been implicated in various diseases, its role in CD is still unclear. Methods: Blood samples were collected from patients with CD and healthy volunteers. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation over Ficoll-Paque and labeled with monoclonal antibodies (CD14-APC and CD36-PE). Flow cytometer CytoFlex is used for analysis. Results: Twenty-nine patients with CD in remission, 42 patients with active CD, and 23 healthy volunteers were included in the study. Our results showed that the frequency of the CD14+CD36+ monocyte subset was increased in PBMCs from patients with active CD compared with patients in remission and healthy controls. However, CD36 on monocytes was lower in CD compared with the healthy controls. CD36 expression was decreased in patients with active CD compared with that of patients with CD in remission and healthy control subjects, but no difference was found between patients with CD in remission and healthy controls. Interestingly, we found negative correlations of CD36 with HBI, SES-CD, C-reactive protein, and neutrophil-to-lymphocyte ratio. Conclusions: These data indicate that monocyte CD36 associates with disease activity in CD and might be a potential biomarker for assessing the activity of CD.

First-in-Human Assessment of Gut Permeability in Crohn’s Disease Patients Using Fluorophore Technology

Background and AimsThe dual sugar absorption test (DSAT) as a classic measure of human intestinal permeability has limited clinical utility due to lengthy and cumbersome urine collection, assay variability, and long turnaround. We aimed to determine if the orally administered fluorophore MB-102 (relmapirazin) (MW=372) compares to lactulose (L) (MW=342) and rhamnose (R) (MW=164)-based DSAT as a measure of gut permeability in people with a spectrum of permeability including those with Crohn’s disease (CD). MethodsWe performed a single center, randomized, open label, crossover study comparing orally administered MB-102 (1.5 or 3.0 mg/kg) to L (1000 mg) and R (200 mg). Adults with active small bowel CD on magnetic resonance enterography (cases) and healthy adults (controls) were randomized to receive either MB-102 or L and R on study day 1, and the other tracer 3-7 days later. Urine was collected at baseline and 1, 2, 4, 6, 8, 10, and 12 hours after tracer ingestion to calculate the cumulative urinary percent excretion of MB-102 and L and R. ResultsNine cases and 10 controls completed the study without serious adverse events. Urinary recovery of administered MB-102 correlated with recovery of lactulose (r-squared = 0.83) for all participants. MB-102 urine recovery also tracked with the L:R ratio urine recovery (r-squared=0.57). In controls, the percentages of L and MB-102 recovered were similar within a narrow range unlike in CD patients. ConclusionsThis first-in-human study of an orally administered fluorophore to quantify gastrointestinal permeability in adults with CD demonstrates that MB-102 is well tolerated, and its recovery in urine mirrors that of percent L and the L:R ratio.

Shorter Crohn’s Disease Duration Is Associated With Better Clinical and Endoscopic Outcomes With Risankizumab in Phase 3 Studies

Early biologic therapy treatment has demonstrated better outcomes in Crohn's disease (CD). We evaluated the impact of CD duration in patients with moderately to severely active CD treated with risankizumab therapy. This post hoc analysis evaluated clinical, endoscopic, and safety outcomes by baseline CD duration (<2, 2-5, >5-10, and >10 years) in patients from ADVANCE, MOTIVATE, and FORTIFY. Pooled induction analyses included patients who received intravenous 600-mg dose of risankizumab or placebo for 12 weeks. Maintenance analyses included patients who responded to induction risankizumab and received subcutaneous 180-mg or 360-mg dose of risankizumab for 52 weeks. Duration subgroups were compared using Cochrane-Armitage trend tests with nominal P values. Among 527 patients who received risankizumab 600-mg induction therapy, higher outcome rates were observed at week 12 among patients with shorter vs longer baseline disease duration (for <2, 2-5, >5-10, and >10 years, clinical remission: 42.7%, 46.9%, 43.5%, and 33.2% [P= .046]; endoscopic response: 48.3%, 36.3%, 32.0%, and 33.4% [P= .025]). Among 298 patients receiving risankizumab (180 mg or 360 mg) maintenance therapy, shorter vs longer baseline disease duration was generally associated with numerically higher endoscopic outcome rates at week 52. Higher clinical remission and endoscopic outcome rates were generally observed with shorter disease duration with 180-mg risankizumab dose only. Adverse event rates were generally similar across duration subgroups. Clinical benefits of risankizumab are observed across disease duration subgroups; clinical and endoscopic outcome rates are higher with risankizumab initiation earlier in the disease course (ClinicalTrials.gov numbers: NCT03105128, NCT03104413, and NCT03105102).

Infliximab serum concentrations in luminal Crohn's disease and its relationship with disease activity: A multicentric cross-sectional study

ObjectivesIn Latin America, experience with monitoring serum Infliximab (IFX) concentrations is scarce. Our study aimed to compare IFX serum concentrations between patients with active disease or in remission. Patients and methodsA cross-sectional study was performed in patients with luminal Crohn's disease (CD) during maintenance treatment with IFX. Patients were classified as in remission or disease activity according to clinical scores and endoscopic, radiological, and laboratory markers. A comparison of IFX trough levels between the two groups was performed. Results80 CD patients were included [41 (51%) in remission and 39 (49%) with active disease]. In the analysis of general disease activity, the median serum levels of IFX in patients with remission and with active CD were 5.63 [0.03–14.40] vs. 3.84 [0.03–14.40] (p=0.287). Furthermore, there was no difference in serum IFX concentrations in endoscopic, radiological, and laboratory activities. Only in the clinical evaluation there was a significant difference in the median serum IFX levels between patients in remission and disease activity, 5.63 [0.03–14.40] vs. 2.14 [0.32–10.54] (p=0.042). ConclusionsIFX serum concentrations during maintenance treatment were similar in patients with luminal CD in remission and general, endoscopic, radiological, and laboratory disease activity. Patients with clinically active disease had lower IFX concentrations than patients in remission.

Is the Mediterranean Diet in Inflammatory Bowel Diseases Ready for Prime Time?

The rising incidence of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), specifically in the developing world, suggests an important environmental effect. Amongst environmental influences, dietary factors, particularly the adoption of a westernized diet, have been specifically noticed. In contrast, the Mediterranean diet (MED), characterized by high intake of fruits, vegetables, whole grains, legumes, nuts, olive oil, and moderate consumption of animal and ultra processed foods, has shown potential positive effects in IBD. Here we conducted a narrative review focusing on the evidence regarding the role of MED in IBD prevention and management. Epidemiological studies suggest inverse association of MED with CD development. Furthermore, adherence to MED has been associated with clinical improvement in active CD and maintenance of lower levels of inflammatory markers in UC, along with improved quality of life and lower mortality rates in IBD patients. Mechanistically, MED promotes a diverse and beneficial gut microbiota, possesses anti-inflammatory properties through polyphenols and dietary fats, and may modulate oxidative stress. In clinical practice, MED may be adapted to diverse disease phenotypes and cultural preferences, and is a sustainable, easy to maintain dietary approach. Current evidence may support the integration of MED into clinical practice in IBD care. In future research, the efficacy of MED in specific IBD phenotypes should be assessed.

Amino acid-based enteral nutrition is effective for pediatric Crohn's disease: a multicenter prospective study.

Exclusive enteral nutrition (EEN) therapy effectively induces remission in pediatric Crohn's disease (CD). However, this may depend on the type of enteral formula used. Moreover, data on the efficacy of amino acid-based EEN are limited. Thus, we aimed to prospectively evaluate the efficacy of amino acid-based formulas for EEN in pediatric patients with active CD. Patients with active CD aged between 6 and 17 years were recruited into this prospective study from four hospitals in China between March 2019 and December 2021. Patients received EEN for 8 weeks. Inflammatory and nutrition-associated indices were evaluated at 0, 4, and 8 weeks after treatment. Paired t-tests and Wilcoxon signed-rank tests were used to compare continuous and categorical variables before and after intervention, respectively. Twenty-four patients were included in the analysis. After an 8-week intervention period, the CD activity index significantly decreased (26.3 ± 12.2 vs 7.1 ± 8.3, P < 0.001). Most patients (66.7%) achieved complete clinical remission. Among the 22 patients who had ulcers and erosions diagnosed endoscopically at baseline, 10 (45.5%) achieved complete mucosal healing. The degree of thickening of the intestinal wall was significantly reduced after EEN intervention, with a transmural healing rate of 42.9%. Furthermore, the serum inflammatory markers decreased and there was a significant improvement in the nutrition-related indices (P < 0.05). There were no severe adverse effects. Amino acid-based EEN is effective and safe for treating pediatric-onset CD. Studies with larger sample sizes and mechanistic and follow-up studies are required to further validate these findings.

Long-term safety of brazikumab in the open-label period of a randomized phase 2a study of patients with Crohn’s disease

BackgroundShort-term efficacy and safety of brazikumab (MEDI2070), a human monoclonal antibody and anti-p19 subunit inhibitor of interleukin-23, was demonstrated in a phase 2a trial in patients with moderate-to-severe active Crohn’s disease (CD). We report brazikumab long-term safety and tolerability from the open-label period of this phase 2a study.MethodsPatients who completed the 12-week, double-blind induction period were eligible for inclusion in an open-label period where all patients received subcutaneous brazikumab (210 mg) every 4 weeks for 100 weeks. Patients had moderate-to-severe active CD and had failed or were intolerant to ≥ 1 anti-tumour necrosis factor alpha (TNFα) agent. Safety assessments included treatment-emergent adverse events (TEAEs); further assessments were pharmacokinetics and immunogenicity.ResultsOf the 104 patients who entered the open-label period, 57 (54.8%) continued to the end of the open-label period and 47 (45.2%) discontinued brazikumab. The most common reasons for discontinuation were lack of response (14.4%), patient decision (12.5%), and TEAEs (11.5%). In total, 44 (84.6%) in the group switching from placebo to brazikumab (placebo/brazikumab) and 43 (82.7%) in the group continuing brazikumab (brazikumab/brazikumab) experienced 1 or more TEAEs. Most TEAEs were mild-to-moderate in severity. Common TEAEs included nasopharyngitis and headache. Numbers of treatment-emergent serious adverse events (TESAEs) were similar between groups. Infections occurred in 40.4% of patients in the placebo/brazikumab group and 50% in the brazikumab/brazikumab group. There were 5 TESAEs of infection, none of which were opportunistic. No major adverse cardiac events, malignancies, or deaths were reported.ConclusionsBrazikumab was well tolerated with an acceptable safety profile over a 100-week period in patients with moderate-to-severe active CD who failed or were intolerant to 1 or more anti-TNFα agents.Trial registrationNCT01714726; registered October 26, 2012.

Blood-Based Biomarkers Reflecting Protease 3 and MMP-12 Catalyzed Elastin Degradation as Potential Noninvasive Surrogate Markers of Endoscopic and Clinical Disease in Inflammatory Bowel Disease.

Chronic inflammation in inflammatory bowel disease (IBD) triggers significant extracellular matrix remodeling, including elastin remodeling, leading to severe clinical complications. Novel methods to assess intestinal tissue destruction may act as surrogate markers of endoscopic disease activity, relieving patients of invasive endoscopy. We explored the noninvasive blood-based biomarkers ELP-3 and ELM-12, measuring elastin degradation in IBD. In a study involving 104 Crohn's disease (CD), 39 ulcerative colitis (UC), and 29 healthy donors, we assessed these biomarkers' association with endoscopic and clinical disease activity using ELISA. Patients were evaluated based on the SES-CD and CDAI for CD patients and modified MES and partial Mayo for UC patients. ELP-3 and ELM-12 were elevated in patients with IBD. Discerning CD patients in endoscopic remission and mild from moderate to severe, ELP-3 provided an AUC of 0.69 and ELM-12 an AUC of 0.73. The ELP-3 biomarker was associated with UC patients and provided the highest diagnostic power of 0.87 for remission vs. active clinical disease. The data suggest an association of ELP-3 with active CD and ELM-12 with endoscopic remission in CD patients. Additionally, ELP-3 could identify UC patients with active clinical disease from patients in remission. The noninvasive biomarkers ELP-3 and ELM-12 could be potential surrogate biomarkers of elastin degradation and endoscopic and clinical disease markers.

Differentiation of Crohn’s disease, ulcerative colitis, and intestinal tuberculosis by dual-layer spectral detector CT enterography

AIMTo investigate the value of radiological features and energy spectrum quantitative parameters in the differential diagnosis of Crohn’s disease (CD), ulcerative colitis (UC), and intestinal tuberculosis (ITB) by dual-layer spectral detector computed tomography (CT) enterography (CTE). MATERIALS AND METHODSClinical and CTE data were collected from 182 patients with CD, 29 with UC, and 51 with ITB. CT images were obtained at the enteric phases and portal phases. The quantitative energy spectrum parameters were iodine density (ID), normalised ID (NID), virtual non-contrast (VNC) value, and effective atomic number (Z-eff). The area under curve (AUC) of the receiver operating characteristic curve (ROC) was calculated. RESULTSThe vascular comb sign (p=0.009) and enlarged lymph nodes (p=0.001) were more common in patients with CD than UC or ITB. In the differentiation of moderate–severe active CD from UC, enteric phase NID (AUC, 0.938; p<0.001) and portal phase Z-eff (AUC, 0.925; p<0.001) had the highest accuracy, which were compared separately. In the differentiation of moderate–severe active CD from ITB, enteric phase NID (AUC, 0.906; p<0.001) and portal phase Z-eff (AUC, 0.947; p<0.001) had the highest accuracy; however, the AUC value was highest when the four parameters are combined (AUC, 0.989; p<0.001; AUC, 0.986; p<0.001; AUC, 0.936; p<0.001; and AUC, 0.986; p<0.001). CONCLUSIONThe present study shows that the combined strategies of four parameters have higher sensitivity and specificity in differentiating CD, UC, and ITB, and may play a key role in guiding treatment.