Crohn's Disease Patients Research Articles

Association of endoscopic findings and histological alterations in pediatric Crohn's disease.

Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) characterized by chronic, transmural, and relapsing inflammation that can affect any segment of the gastrointestinal tract, from the oral cavity to the anus (1). The clinicopathological association of various endoscopic abnormalities in CD is under study. An analytical study was conducted on patients under the age of 15 who underwent esophagoscopy and/or colonoscopy for suspected IBD at a pediatric hospital between 2015 and 2022 (Reg. No. 3318-0000206). Subjects with normal histopathological findings and those with a histological diagnosis of CD were included. The prevalence of different endoscopic alterations and their association with histopathological abnormalities were compared between patients with Crohn's disease (CD) and those with normal histology (NCD). Of the 502 endoscopies performed during this period, 22 subjects with CD and 14 children with NCD were included. Endoscopic normality, defined as the absence of mucosal abnormalities, was higher among NCD patients (43%), while the most prevalent macroscopic abnormality in CD patients was the presence of ulcers.

Crohn's disease and ulcerative colitis share two molecular subtypes with different mechanisms and drug response.

Several therapies have been approved to treat crohn's disease (CD) and ulcerative colitis (UC), indicating that both diseases may share the same molecular subtypes. The aim of this study is to identify shared patient subtypes with common molecular drivers of disease. Five public datasets with 406 CD and 421 UC samples were integrated to identify molecular subtypes. Then, the patient labels from six independent datasets and eight treatment datasets were predicted for validating subtypes and identifying the relationship with response status of corticosteroids, infliximab, vedolizumab, and ustekimumab. Two molecular subtypes were identified from the training datasets, in which CD and UC patients were relatively evenly represented in each subtype. We found six S1-specific gene modules related to innate/adaptive immune responses and tissue remodeling and nine S1-specific cell types (cycling T, Tregs, cd8+ lamina propria, follicular B, cycling B plasma, inflammatory monocytes, inflammatory fibroblast, and post-capillary venules). Subtype S2 was associated with three modules related to metabolism functions and four cell types (immature enterocytes, transit amplifying, immature goblet and WNT5B+). The subtypes can be replicated in six independent datasets based on a 20-gene classifier. Furthermore, response rates to four treatments in subtype S2 were significantly higher than those in subtype S1. This study discovered and validated a robust transcriptome-based molecular classification shared by CD and UC and built a 20-gene classifier. Because two subtypes have different molecular mechanisms and drug response, our classification may aid interpretation of heterogeneous molecular and clinical information in IBD patients.

S1221 Risankizumab Sustains Remission and Improves Anti-TNF-Induced Psoriasiform Dermatitis in Well Controlled Crohn's Disease Patients Switched From Anti-TNF Therapy

S1221 Risankizumab Sustains Remission and Improves Anti-TNF-Induced Psoriasiform Dermatitis in Well Controlled Crohn's Disease Patients Switched From Anti-TNF Therapy

S1142 Recurrence Patterns in Crohn's Disease Patients With End Ostomies: Insights From the Cleveland Clinic IBD Ostomy Research Registry

S1142 Recurrence Patterns in Crohn's Disease Patients With End Ostomies: Insights From the Cleveland Clinic IBD Ostomy Research Registry

The Effect of Drugs on the Intestinal Microbiota in Crohn's Disease.

We took advantage of a single-center cross-sectional study to investigate the effect of different drugs on intestinal microbiota and function in Crohn's disease. We studied the difference in fecal microbiota of Crohn's disease patients treated with mesalazine, azathioprine, and infliximab, as well as untreated patients, by metagenome and screened for differential microbiota. Further, we investigated functional differences in intestinal microbiota among the four groups. Through metagenomic sequencing, we found that there was no difference between the four groups in ACE and Chao1 indices, but IFX and mesalazine improved species diversity and homogeneity compared to the untreated group, as evidenced by statistically significant differences in the Shannon index, Simpson index, and pielou_evenness. In addition, beta diversity suggested a difference between groups, but the difference was not significant. Non-parametric tests revealed differences between the four groups at the phylum level, class level, and genus level. Further analysis by LEfSe analysis revealed that the level of short-chain fatty acid-producing microbiota was increased in the treated groups, while there was no difference between the treated groups when compared to each other. Finally, the KEGG database and EggNOG database revealed that there were functional differences in intestinal microbiota among the four groups, including microbial metabolism pathway, cysteine and methionine metabolism pathway, cytoskeleton, etc. Conclusions: Mesalazine, azathioprine, and infliximab can all affect the intestinal microbiota and function in patients with Crohn's disease, and the drugs may alleviate intestinal inflammation in patients with Crohn's disease by modulating the intestinal microbiota.

Assessing the impact of dietary interventions on nutritional adequacy in adult Crohn's disease patients: preliminary results

Assessing the impact of dietary interventions on nutritional adequacy in adult Crohn's disease patients: preliminary results

The impact of achieving remission in inflammatory bowel disease on plasma matrix -carboxyglutamate protein levels

Matrix -carboxyglutamic acid (MGLA) protein is a vitamin K dependent peptide which contributes to the immunomodulatory activity of mesenchymal stromal cells. There is a possible association between MGLA protein and inflammatory bowel disease (IBD) which is divided into Crohn’s disease (CD) and ulcerative colitis (UC). However, little is known about the clinical utility of MGLA protein in IBD patients. This study aimed to assess the impact of achieving remission on the serum MGLA protein levels in IBD patients. This prospective observational study included 60 newly diagnosed IBD patients. All patients were subjected to full clinical, laboratory, radiological, and histopathological assessment of IBD at baseline and six months after initiating treatment. Serum MGLA protein level was assessed using an enzyme-linked immunosorbent assay. There were 29 (48.3%) UC cases and 31 (51.67%) CD cases. We observed a significant decrease in serum MGLA protein levels after 6 months of treatment compared to pretreatment values in UC patients (120.490 ± 26.273 vs. 26.320 ± 17.378 nmol/L, p<0.001) and CD patients (125.576 ± 28.208 vs. 28.520 ± 18.443 nmol/L, p<0.001). Serum MGLA protein levels were significantly higher in non-remittent patients compared to remittent UC patients before treatment (142.556 ± 17.096 vs. 110.560 ± 23.659 nmol/L, p<0.001) and after six months of treatment (51.222 ± 4.410 vs. 15.114 ± 3.302 nmol/L, p<0.001). Serum MGLA protein levels were significantly higher in non-remittent patients compared to remittent CD patients before treatment (150.727 ± 7.198 vs. 111.743 ± 25.718 nmol/L, p<0.001) and after six months of treatment (52.182 ± 5.269 vs. 15.506 ± 4.475 nmol/L, p<0.001). This response was irrespective of the therapeutic modality. In conclusion, achievement of remission in IBD patients resulted in a significant decrease in serum MGLA protein levels.

Predicting mucosal inflammation in IBD patients using patient-reported symptom scores and a faecal calprotectin home test: protocol for a multicentre prospective validation study

IntroductionCrohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) with a relapsing-remitting nature. With adequate non-invasive prediction of mucosal inflammation, endoscopies can be prevented and treatment optimised earlier...

The Epidemiology and Clinical Management of Short Bowel Syndrome and Chronic Intestinal Failure in Crohn's Disease in Italy: An IG-IBD Survey.

Limited data exist on the epidemiology and clinical management of short bowel syndrome (SBS) and chronic intestinal failure (CIF) in Crohn's disease (CD). This study aimed to evaluate these aspects in Italy. Members of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) were invited to complete a cross-sectional web survey. A subgroup analysis examined the influence of different clinical settings on SBS and CIF management in CD. A total of 47/128 (36.7%) IG-IBD centers participated. Among them, 31.9% were teduglutide (TED) prescribers, and 48.9% were academic centers. The median estimated prevalence of CIF among small bowel CD patients was 1%, and it was significantly higher in academic centers (2.0% [IQR 1-5%] vs. 0.13% [IQR 0-1%], p = 0.02). Seventy-eight percent of centers managed fewer than 10 SBS and CD patients. Routine small bowel measurement and nutritional assessment were performed in only 15% and 42.6% of centers, respectively. TED was prescribed by 12 centers to 35 patients, with a treatment success rate exceeding 50% in 81.8% of centers. The estimated prevalence of CIF in CD patients with small bowel involvement in Italy is 1%. The diagnosis and management practices for SBS and CIF are suboptimal, and TED use is limited.

Targeting NCAPD2 as a Therapeutic Strategy for Crohn's Disease: Implications for Autophagy and Inflammation.

Our earlier studies identified that non-SMC condensin I complex subunit D2 (NCAPD2) induces inflammation through the IKK/NF-κB pathway in ulcerative colitis. However, its role in the development of Crohn's disease (CD) and the specific molecular mechanism still need to be further studied. NCAPD2 expression in clinical ileal CD mucosa vs normal mucosa was examined, alongside its correlation with CD patients' clinical characteristics via their medical records. The biological function and molecular mechanism of NCAPD2 in CD were explored using a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD mouse model, along with immunofluorescence, western blot, quantitative real-time PCR, immunohistochemistry, hematoxylin and eosin staining, and cell functional analysis. NCAPD2 was overexpressed in CD tissues and significantly correlated with disease activity in CD patients (P = .016). In a TNBS-induced CD mouse model, NCAPD2 knockdown inhibited the development of TNBS-induced intestinal inflammation in mice. In addition, we found that NCAPD2 inhibited autophagy. Mechanistically, NCAPD2 promoted the phosphorylation of mammalian target of the rapamycin (mTOR) and its direct effector S6K and downregulated the expression of autophagy-related proteins Beclin1, LC3II, and Atg5. In addition, NCAPD2 activates the NF-κB signaling pathway, and the downstream inflammatory factors are continuously released, leading to the persistence of inflammation. Our results show that NCAPD2 suppresses autophagy and worsens intestinal inflammation by modulating mTOR signaling and impacting the NF-κB pathway, suggesting a critical role in CD progression. Targeting NCAPD2 could be a promising therapeutic approach to stop CD advancement.

Real-life effectiveness of allogeneic expanded adipose-derived mesenchymal stem cell therapy for perianal fistulizing refractory Crohn's disease

BackgroundReal life data about the long-term efficacy of darvadstrocel for treating perianal fistulas in Crohn's disease (CD) remain scarce. Aim: To report the effectiveness and safety of darvadstrocel therapy to close perianal fistula in a real-life cohort of CD patients. MethodsAll patients with CD suffering complex draining perianal fistulas who consecutively underwent administration of a single local injection of darvadstrocel at two centres were followed up and evaluated. The primary endpoint was clinical remission (closure of all external openings with no discharge at pressure) at week 24. Combined remission (defined as clinically plus MRI-assessed fistula closure) were also assessed at week 24 and 52. ResultsA total of 36 CD patients (19 Male, mean age 38.5 years) were included with a median follow up of 16 months. Clinical remission was achieved in 17 out of 36 patients (47.2 %) and combined remission in 15 out of 36 patients (41.6 %) at week 24. At week 52, clinical and combined remission was achieved in 17 out of 36 patients (47.2 %) and in 15 out of 33 evaluable patients (45.4 %), respectively. ConclusionIn this real-world setting, a successful response to darvadstrocel therapy based on clinical remission was reported in around half of the patients and combined remission including radiological assessment in more than 4 out of 10 patients.

A trend analysis of inflammatory bowel disease in non-endemic era (1993-2023)

Aims: In this study, we aimed to evaluate the demographic and epidemiological trends of ulcerative colitis (UC) and Crohn’s disease (CD) in non-endemic era for inflammatory bowel disease (IBD) during the past three decades. Methods: UC and CD patients who had follow-up at least 6 months between June 1993 and February 2023 were evaluated retrospectively. Electronic medical databases, personal queries and IBD registries have all been used to collection data on the clinical and demographic characteristic of all patients. Results: A total of 1549 adult patients with UC and CD were admitted to study. UC was diagnosed in 873 (56.4%) patients (male 538, 61.6%) and CD was diagnosed in 676 (43.6%) patients (male 404, 59.8%). Median total disease duration was 8.3 years in UC group, as well as 6.8 years in CD group. In patients with UC, proctitis was 154 (17.6%), left sided colitis was 410 (47%) and extensive colitis was 309 (35.4%). In CD patients, ileal involvement was found in 297 (43.9%), colonic in 76 (11.2%), ileo-colonic in 299 (44.2%) and isolated upper gastrointestinal involvement in 4 (0.6%) cases. 529 (78.3%) patients had inflammatory disease (non-stenosing non-penetrating behavior), 45 (6.7%) had stenosing behavior, 102 (15.1%) had penetrating behavior, as well as 196 (29%) patients had perianal disease. Mesalazine 658 (75.4%) and thiopurine 397 (45.5%) were the most frequently used conventional treatments for UC, while thiopurine 304 (45%) was most commonly used for CD patients. In the last two-decade, proportion of the biologic usage were 27.9% and 32.1% in UC patients 28.5% and 31.4% in CD patients respectively. Over the three decades, abdominal surgery was 49.2%, 27.8% and 36.3% in CD and colectomy rates was 2.0%, 2.7% and 3.7% in UC patients. While the rate of UC patients has slightly decreased to 98 (61.6%), 401 (58.5%) and 374 (53%) frequency of CD patients has increased to 61 (38.4%), 284 (41.5%) and 331 (47%). Over the course of three decades, there were more UC patients than CD patients, however proportion of UC/CD has been continuously decreased (1.61, 1.41 and 1.13) for three decades respectively. Conclusion: Our study showed that the frequency of UC and CD has significantly increased during the previous three decades in non-endemic era for IBD. While the frequency of UC patients has slightly decreased, that of CD patients has steadily increased over the past three decades. Although the use of biologics has significantly increased, proportions of the major abdominal surgeries and colectomies has not prominently changed.

Biochemical Modulators of Tight Junctions (TJs): Occludin, Claudin-2 and Zonulin as Biomarkers of Intestinal Barrier Leakage in the Diagnosis and Assessment of Inflammatory Bowel Disease Progression.

Considering the increasing worldwide prevalence of inflammatory bowel disease (IBD), the early diagnosis of this disease is extremely important. However, non-invasive diagnostic methods remain limited, while invasive techniques are the most commonly used in daily practice. Therefore, there is a serious need to find new non-invasive biomarkers of IBD. The serum profiles of occludin, claudin-2, and zonulin were assessed in IBD patients using the ELISA method. The levels of the analyzed biomarkers were measured before and after a year of anti-inflammatory treatment, which was a tumor necrosis factor α (TNF-α) inhibitor (adalimumab) in patients with ulcerative colitis (UC) and conventional therapy in patients with Crohn's disease (CD). In IBD patients, the serum level of occludin (p < 0.001) decreased compared to healthy individuals, while the level of claudin-2 (p < 0.001) increased. Additionally, zonulin (p < 0.01) concentration increased in CD patients compared to the control group. The highest diagnostic ability was presented by occludin measurements with the area under the curve (AUC) of 0.959 (95% CI 0.907-1) in UC and 0.948 (95% CI 0.879-1) in CD. Claudin-2 also demonstrated very good ability in diagnosing UC and CD with AUC values of 0.864 (95% CI 0.776-0.952) and 0.896 (95% CI 0.792-0.999), respectively. The ability of zonulin to diagnose CD was estimated as good with an AUC of 0.74 (95% CI 0.598-0.881). Moreover, a significant correlation was identified between C-reactive protein (CRP), claudin-2 (r = -0.37; p < 0.05), and zonulin (r = -0.44; p < 0.05) in UC patients. Treatment with adalimumab improved the level of occludin, claudin-2, and zonulin in UC patients, while anti-inflammatory conventional therapy decreased the concentration of zonulin in CD. Occludin and claudin-2 measurements present significant utility in diagnosing both UC and CD, while zonulin assessments may be useful in CD diagnosis. Additionally, claudin-2 and zonulin measurements may be helpful in evaluating the intensity of the inflammatory process. Anti-TNF-α treatment improved the value of occludin, claudin-2, and zonulin, indicating its beneficial effect on the integrity of tight junctions in UC.

Risk Factors for Gallstones in Crohn's Disease: A Systematic Review and Meta-Analysis.

Crohn's disease (CD) have an increased risk of gallstone disease. We aimed to systematically evaluate the prevalence rate and relevant risk factors of gallstones in CD patients. A comprehensive search of PubMed, Embase, and Web of Science databases from inception to September 10, 2023, identified studies investigating risk factors for gallstone development among CD patients. Gender, age, body mass index, disease duration, disease site, stenosis, prior surgery, hospitalization times, corticosteroids, immunomodulators, and total parenteral nutrition (TPN) were assessed as potential risk factors. Odds ratios (OR) and confidence intervals (CI) were calculated. Among 1184 articles, 11 observational studies (3588 patients) were included. The prevalence of CD patients with gallstones was approximately 14.7%. Factors significantly associated with increased gallstone risk included Age ≥ 40years old (OR 3.06, 95% CI 2.09- 4.48), disease duration > 15years (OR 3.01, 95% CI 2.06-4.42), lifetime surgery(OR 2.50, 95% CI 1.99-3.12), disease located in ileocolon (OR 1.38, 95% CI 1.04-1.83) and ileocecal(OR 1.93, 95% CI 1.16-3.21), multiple hospitalizations(OR 4.26, 95% CI 2.43-7.46), corticosteroid treatments(OR 2.65, 95% CI 1.52-4.63), immunomodulator therapy(OR 1.94, 95% CI 1.12-3.38), and TPN use(OR 2.66, 95% CI 1.29-5.51). Sex, stenosis, overweight, or low weight did not significantly increase the risk of gallstone developing. Age, long disease duration, specific disease locations (ileocolon, ileocecal), surgery, number of hospitalizations, corticosteroids, immunomodulator therapy, and TPN were identified as factors that increased the risk of gallstones in CD patients. About 14.7% of CD patients experience gallstones, so raising awareness and implementing prevention are needed. PROSPERO (CRD42023449299).

Subcutaneous infliximab in Crohn’s disease patients with previous immunogenic failure of intravenous infliximab

PurposeImmunogenicity is a major reason for secondary loss of response to infliximab (IFX). Recent work suggested potentially lower immunogenicity of subcutaneous (SC) compared to intravenous (IV) IFX. However, it is unknown whether re-exposure to IFX SC after secondary loss of response and immunogenicity to its intravenous formulation is safe and effective.MethodsIn a retrospective cohort study conducted at two medical centers, patients with clinically (Harvey-Bradshaw Index ≥ 5) and/or biochemically (fecal calprotectin > 250 µg/g) active Crohn’s disease (CD) and previous immunogenic failure of IFX IV underwent exposure to IFX SC. Harvey-Bradshaw Index, fecal calprotectin, IFX serum concentration, and anti-drug antibodies were assessed until month 12.ResultsTwenty CD patients were included. The majority of patients (90%) had previous treatment with three or more biologics. Fifteen (75%) and ten (50%) of 20 patients continued IFX SC treatment until months 6 and 12, respectively. No immediate hypersensitivity reactions were observed. Two patients discontinued IFX SC treatment because of delayed hypersensitivity at week 2 and week 4. IFX serum concentrations increased from baseline to month 12, while anti-drug antibody levels decreased. Combined clinical and biochemical remission at month 12 was observed in seven of 20 patients (35%).ConclusionSubcutaneous infliximab treatment of Crohn’s disease patients with previous immunogenic failure of intravenous infliximab was well tolerated and effective in a cohort of patients with refractory Crohn’s disease.

Epidemiological investigation of different types of Crohn's disease patients undergoing first abdominal surgery in the era of biological agents: a population-based cohort study.

Before the era of biological agents, most Crohn's disease patients required at least one intestinal resection surgery after diagnosis. However, clinical data regarding the abdominal surgery rates for Crohn's disease patients in the era of biological agents is not yet fully clear and needs to be updated. We retrospectively collected clinical data from 1115 Crohn's disease patients diagnosed and treated medically at The Second Xiangya Hospital of Central South University from January 2016 to January 2024. Using abdominal intestinal resection surgery as a clinical outcome, propensity score matching was employed to eliminate confounding factors. We explored the timing and proportion of abdominal surgery in patients with different Montreal classifications of Crohn's disease during the natural course of the disease, as well as the impact of the duration of the natural course and the use of biological agents on surgical outcomes. Montreal classification type B had the greatest impact on Crohn's disease surgery, especially with a higher proportion of type B3 patients undergoing surgery. Type A1 Crohn's disease patients underwent surgery earlier than types A2 and A3. The occurrence of behavior changes (B Change) during the natural course of the disease is a poor prognostic signal, indicating a significantly increased likelihood of surgery. The duration of the natural course from the onset of gastrointestinal symptoms to diagnosis and clinical observation outcomes did not directly affect the likelihood of surgery in Crohn's disease patients. Compared with Crohn's disease patients who did not receive biological agents, the surgery rate was significantly lower in patients who used biological agents. Additionally, Crohn's disease patients who received biological agents within 1 month of diagnosis had a significantly lower likelihood of undergoing surgical intervention. Moreover, Crohn's disease patients who received biological agent treatment within 19 months of the onset of gastrointestinal symptoms also had a significantly lower likelihood of undergoing surgery than other Crohn's disease patients. In the era of biological agents, the risk of surgical intervention varies among Crohn's disease patients with different Montreal classifications, particularly when there is type B3 disease or a B Change. Clinicians should pay closer attention to surgical indications in such cases. For Crohn's disease patients, shortening the natural course before diagnosis and early use of biological agents after diagnosis can significantly reduce the risk of abdominal surgery.

Evaluation of Selenium Concentrations in Patients with Crohn's Disease and Ulcerative Colitis.

In this study, serum selenium levels in patients with Crohn's disease (CD) and ulcerative colitis (UC) were evaluated to identify potential predictive markers of disease activity. Conducted in 100 inflammatory bowel disease (IBD) patients (54 CD, 46 UC) and 100 healthy controls, this research provides novel insights through focusing on the regional selenium status of people with IBD in the Polish population, a demographic with limited existing data. Selenium concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). Significantly lower levels of selenium were observed in CD (64.79 µg/L ± 12.15 µg/L) and UC (68.61 µg/L ± 11.43 µg/L) patients when compared with the controls (90.52 ± 12.00 µg/L, p < 0.0001). Regression analysis identified leukocyte and erythrocyte counts and bilirubin as significant predictors of selenium levels in UC patients, while no significant predictors were found for CD. The findings suggest that selenium deficiency is linked to IBD and may serve as a non-invasive biomarker for disease severity, particularly in UC. This practical approach offers a potential alternative to invasive procedures such as endoscopy for monitoring disease progression. However, further research is needed to confirm these findings in larger populations and explore the therapeutic role of selenium supplementation in IBD management.

Detecting and characterizing creeping fat in Crohn’s disease: agreement between intestinal ultrasound and computed tomography enterography

ObjectivesCreeping fat (CF) is associated with stricture formation in Crohn’s disease (CD). This study evaluated the feasibility of intestinal ultrasound (IUS) for semiquantitative analysis of CF and compared the agreement between IUS and computed tomography enterography (CTE).MethodsIn this retrospective study, we recruited consecutive CD patients who underwent IUS and CTE. CF wrapping angle was analyzed on the most affected bowel segment and was independently evaluated by IUS and CTE. We evaluated the wrapping angle of CF in the cross- and vertical sections of the diseased bowel. CF wrapping angle was divided into < 180° and ≥ 180°. IUS performance was assessed using CTE as a reference standard, and IUS interobserver consistency was evaluated.ResultsWe enrolled 96 patients. CTE showed that CF wrapping angle was < 180° in 35 patients and ≥ 180° in 61 patients. We excluded three cases in which the observation positions were inconsistent between the IUS and CTE. Excellent agreement was shown between US and CTE (82/93, 88.2%). The eleven remaining cases showed inconsistencies mostly in the terminal ileum (n = 5) and small intestine (n = 4). Total agreement between IUS observers was 89.6% (86/96, κ = 0.839, p = 0.000), with perfect agreement for the ileocecal and colonic segments (35/37, 94.6% and 20/21, 95.2%, respectively) and moderate agreement for small intestinal segments (16/21, 76.2%).ConclusionsIUS could be of value and complementary to CTE for assessing CF, particularly in patients with affected terminal ileum and colon. IUS is a non-invasive technique for monitoring CD patients.Critical relevance statementIn our study, excellent agreement was shown between intestinal US observers as well as between US and CT enterography (CTE) for assessing creeping fat (CF), which showed that ultrasound could be of value and complementary to CTE.Key PointsCreeping fat (CF) is a potential therapeutic target in Crohn’s disease.Excellent agreement was shown between US and CT Enterography (CTE) for assessing CF.Ultrasound could be complementary to CTE for assessing CF.Graphical

Outcomes of patients with prior biologic intolerance are better than those with biologic failure in clinical trials of inflammatory bowel disease

Abstract Background and Aims Inflammatory bowel disease (IBD) trials often stratify patients by prior biologic exposure, including prior biologic failure or intolerance. This study aimed to assess clinical outcomes in IBD patients with prior biologic failure versus intolerance treated with ustekinumab or vedolizumab. Methods A post-hoc analysis of ulcerative colitis (UC) and Crohn’s disease (CD) clinical trials for ustekinumab (UNITI, UNIFI) and vedolizumab (GEMINI-1, GEMINI-2) was performed. Clinical response, clinical remission, and endoscopic improvement (for UC) were compared among biologic naïve, biologic-failure, and biologic intolerant patients. Statistical analyses, including chi-square tests and logistic regression, were performed. Results 1178 UC and 1439 CD patients received either ustekinumab or vedolizumab. In UC, biologic intolerant patients exhibited higher clinical response (54.7% vs. 38.8%, aOR 1.87 [95% CI 0.93-3.73]), clinical remission (25.0% vs. 11.0%, aOR 2.84 [95% CI 1.47-5.49]), and endoscopic improvement (40.6% vs. 24.8%, aOR 2.76 [95% CI 1.28-5.94]) compared to biologic failure, with outcomes similar to biologic naïve patients. In biologic-intolerant CD patients, clinical response was similar between prior biologic failure and intolerance (34.2% vs 32.8%), but after adjustment for potential confounders, biologic intolerance was associated with higher odds of clinical response (aOR: 1.67, 95% CI 1.09-2.55), with no significant difference observed for clinical remission (aOR: 1.48, 95% CI 0.88-2.49). Conclusion Improved treatment outcomes were generally observed in patients with biologic intolerance compared to failure, especially in UC, where outcomes were similar to biologic naïve patients. Future clinical trials should meticulously differentiate prior biologic failure versus intolerance to mitigate potential bias.

Prolonged Time to Diagnosis of Crohn’s Disease in Patients With Perianal Fistulas Negatively Affects Long-Term Outcomes

Abstract Background and Aim This study aims to evaluate the effect of time to Crohn’s disease (CD) diagnosis on perianal fistula (PAF) outcomes in patients with a fistula as the first manifesting sign. Methods In this multicenter, retrospective study, CD patients with a PAF preceding CD diagnosis between November 2015 and June 2022 were included. The primary outcome parameter was the time to CD diagnosis and its correlation with long-term outcomes. Results In total, 126 patients with a PAF prior to CD diagnosis were identified. The median time to CD diagnosis was 15.0 months (IQR 3.8-47.3). A total of 49 patients (38.9%) had a clinically closed fistula of which 21 patients (42.9%) achieved radiological healing. Twenty-five patients (19.8%) underwent defunctioning, of which 9 patients (36.0%) needed proctectomy. Median time to CD diagnosis was shortest in patients with radiological healing (4.0 months, IQR 2.0-16.5) or clinical closure without radiological healing (11.0 months, IQR 3.0-47.8). In patients without fistula closure (n = 51), the median time to CD diagnosis was significantly longer compared to patients with fistula closure, 18.0 months vs 8.0 months (p = 0.031). In patients who needed defunctioning, the median time to diagnosis was more than twice as long compared to patients without defunctioning, 30.0 months vs 12.0 months (p = 0.054). Conclusion A prolonged time to CD diagnosis in patients with a PAF as a manifesting sign is associated with worse long-term outcomes. Patients in whom radiological healing could be achieved had the shortest time to CD diagnosis, emphasizing the relevance of increased clinical awareness of underlying CD in fistula patients.