Pro-motility Preparation Protocol May Reduce the Rates of Failed Patency Capsule Among Patients with Crohn's Disease in Clinical Remission.

BACKGROUND: Patency capsule (PC) ingestion is commonly used to minimize capsule retention in high-risk patients with Crohn's disease (CD). However, false-positive rates remain high, precluding the use of video capsule endoscopy (VCE). We aimed to compare the efficacy of two preparation protocols in reducing failed PC rates in patients with CD. METHODS: This bi-center retrospective case-control study included adult patients with small-bowel CD in clinical remission who underwent PC ingestion. The pro-motility group followed a low-residue diet, then a clear fluid diet, and took bisacodyl after ingestion, while the control group followed only a clear fluid diet. The primary outcome was failed PC, defined as the absence of PC excretion or presence on abdominal X-ray at 30 h post-ingestion. Multivariable logistic regression was used to identify predictors of failed PC. RESULTS: Among 273 patients (83 in the pro-motility group, 190 controls), the pro-motility group was older (median 36 [27-48] vs. 31 [24-43], p = 0.012) and had a lower rate of B2/3 disease phenotype (32.5 vs. 53.1%, p = 0.002) compared to controls. The pro-motility group also had a lower failed PC rate (12.0 vs. 24.7%, p = 0.023). Longer disease duration (adjusted odds ratio (AOR) 1.053, 95% confidence interval (CI) 1.016-1.091, p = 0.005) increased the odds of failed PC, while the pro-motility protocol was protective (AOR 0.438, 95% CI 0.200-0.956, p = 0.038), outweighing the influence of B2/3 disease phenotype (AOR 1.743, 95% CI 0.912-3.332, p = 0.093). CONCLUSIONS: The pro-motility preparation protocol could substantially improve the success rates of the small-bowel patency test in patients with CD undergoing PC ingestion, potentially reducing the risk of capsule retention and associated complications.

Defining mucosal healing in randomized controlled trials of inflammatory bowel disease: A systematic review and future perspective.

BACKGROUND: Mucosal healing (MH) is an established treatment goal in inflammatory bowel disease (IBD). However, various definitions of MH exist. We aimed to identify how MH is defined in randomized controlled trials (RCTs) in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We searched MEDLINE, EMBASE, and the Cochrane library from inception to December 2023 for phase 2 and 3 RCTs of advanced therapies in IBD. RESULTS: One hundred forty-four studies were included, 72 in UC and 72 in CD, published between 1997 and 2023. In UC, 64% (46/72) RCTs reported MH as an endpoint. 12 definitions of MH were found, from endoscopic assessment alone (35/46; 76%) to the more recent combination of histology and endoscopy (10/46; 22%). 96% (44/46) of studies used the Mayo Endoscopic Subscore. In CD, reporting of MH lagged behind UC, with only 12% (9/72) of trials specifically defining MH as an endpoint, 7 as "absence of ulceration," 2 as Simplified Endoscopic Score for CD score ≤2 or 0. Histological assessment was performed in 3 RCTs of CD. Centralized reading of endoscopy was used in 48% (35/72) of RCTs of UC and 22% (16/72) of CD. Only 1 RCT included transmural healing as an endpoint. CONCLUSIONS: A standard definition of MH in IBD is lacking. Definitions have evolved particularly in UC, which now includes the addition of histological evaluation. Transmural healing holds promise as a future target in CD. We support a greater standardization of definitions as we expect endpoints to become increasingly stringent and multimodal with computers automating the assessment.

Serum matrix metalloproteinase-7, Syndecan-1, and CA 19-9 as a biomarker panel for diagnosis of pancreatic ductal adenocarcinoma.

AIMS AND BACKGROUND: Matrix metalloproteinase-7 (MMP-7) and Syndecan-1 (SDC1) are involved in multiple functions during tumorigenesis. We aimed to evaluate the diagnostic and prognostic performance of these serum proteins, as potential biomarkers, in patients with pancreatic ductal adenocarcinoma (PDAC) and benign pancreatic cysts. METHODS: In this case-control study, patients with newly diagnosed PDAC (N = 121) were compared with the benign cyst (N = 66) and healthy control (N = 48) groups. Serum MMP-7 and SDC1 were measured by ELISA. The diagnostic accuracy of their levels for diagnosing PDAC and pancreatic cysts was computed, and their association with survival outcomes was evaluated. RESULTS: MMP-7 median serum levels were significantly elevated in the PDAC (7.3 ng/mL) and cyst groups (3.7 ng/mL) compared with controls (2.9 ng/mL) (p < 0.001 and 0.02, respectively), and also between the PDAC and cyst groups (p < 0.001), while SDC1 median serum levels were significantly elevated in PDAC (43.3 ng/mL) compared with either cysts (30.1 ng/mL, p < 0.001) or controls (31.2 ng/mL, p < 0.001). The receiver operating characteristic curve analysis area under the curve in PDAC versus controls was 0.90 and 0.78 for MMP-7 and SDC1, respectively, while it was 1.0 for the combination of the two and CA 19-9 (p < 0.001). The combination of the three biomarkers had a perfect sensitivity (100%). CONCLUSIONS: Due to its high sensitivity, this biomarker panel has the potential to rule out PDAC in suspected cases.

Differences in disease characteristics and treatment exposures between paediatric and adult-onset inflammatory bowel disease using a registry-based cohort.

BACKGROUND: Previous studies highlighted a more extensive phenotype for paediatric-onset than adult-onset inflammatory bowel disease (IBD). However, most lacked long-term follow-up, and some were conducted before the era of biologics. AIMS: The aim of this study is to compare disease characteristics and treatment exposures between paediatric-onset and adult-onset IBD. METHODS: From a registry that periodically and uniformly retrieves demographics, disease characteristics/phenotype, and treatments, we compared the characteristics of paediatric-onset (diagnosed at ≥6 and <18 years) and adult-onset IBD, diagnosed during 2000-2022 and with ≥12 months follow-up. RESULTS: Of the 2837 patients with Crohn's disease and 1332 with ulcerative colitis, 3316 had adult-onset and 853 paediatric-onset IBD. The median follow-up was 6 years. Patients with paediatric-onset presented with more extensive disease and received more intensified therapies, including biologics and JAK inhibitors than those with adult-onset IBD. Paediatric-onset ulcerative colitis showed a higher prevalence of E3 extensive colitis including pancolitis and a greater requirement for systemic steroids, immunomodulators, and biologics than adult-onset ulcerative colitis. Paediatric-onset versus adult-onset Crohn's disease exhibited greater L3 ileocolonic involvement and perianal disease phenotype, and higher exposure to immunomodulators and biologics. Kaplan-Meier curve and Cox proportional hazards analyses showed significantly lower 15-year biologic-free survival from diagnosis among those with paediatric-onset IBD than with adult-onset IBD (p = <0.001), indicating greater and earlier use of biologics in the former. CONCLUSIONS: Paediatric-onset presents with more extensive disease with higher exposures to immunomodulators and biologic therapies than adult-onset IBD.

Fecal calprotectin diagnostic level gradient along the small bowel in patients with Crohn's disease.

BACKGROUND AND AIMS: Fecal calprotectin (FC) is known to be a sensitive biomarker of colonic inflammation but to a lesser degree of small bowel (SB) inflammation. Moreover, data on FC's diagnostic levels in different SB segments are scarce. We aimed to examine FC's diagnostic levels along the SB-axis in CD. METHODS: This was a post-hoc aggregated analysis of five prospective studies of adult CD patients, who underwent FC testing and SB video capsule endoscopy (VCE). Lewis score (LS) inflammation in different SB segments was tested for correlation with FC level after exclusion of colonic disease. The diagnostic levels of FC for SB inflammatory topographical-gradient were assessed using a receiver operating characteristic. RESULTS: 214 patients were included (age:30 [24-43] year-old, males-57%). For a similar SB inflammatory-activity (LS≥135), FC levels incrementally increased from proximal to distal SB segments (63 [30-121] versus 190 [78-549], p=0.005) and from distal SB segment to the colon (190 [78-549] versus 542 [185-1000], p=0.010). The best FC cutoffs to identify isolated mild proximal/distal SB-inflammation (LS≥135) were 77µgg and 123µgg, respectively. A cutoff of 234µgg was best to detect more significant proximal inflammation (LS≥350) when only mild distal SB-inflammation was present. In sensitivity analyses, this proximal-to-distal FC gradient was maintained when LS≥350 and LS≥790 were used as the inflammatory reference-values. Unlike FC, the magnitude of CRP elevation was unrelated to the topography of inflammation along the SB-axis. CONCLUSIONS: FC may serve as a topographical biomarker of CD-activity, with its sensitivity to identify mucosal inflammation increases from proximal to distal SB segments.

Unsedated colonoscopy utilizing virtual reality distraction: a pilot-controlled study.

BACKGROUND: Sedation increases colonoscopy risks and prolongs recovery time. We examined whether virtual reality (VR) can substitute for sedation. The primary outcome was the overall satisfaction of patients who underwent colonoscopy with VR headset compared with patients who underwent standard sedation. Pain during the procedure, polyp detection rate (PDR), colonoscopy duration, post-colonoscopy adverse events, post-colonoscopy recovery, time-to-return to daily functions, and turnaround time at the endoscopy unit were secondary outcomes. METHODS: The study was approved by Sheba Medical Center's ethics committee IRB number 21-8177-SMC. Sixty patients were sequentially enrolled in a 1:1 ratio to either standard sedated colonoscopy or VR-unsedated procedure, and all patients signed a written informed consent. 28/30 patients successfully completed the colonoscopy using VR headset. Overall satisfaction score was comparable between the groups. RESULTS: There was no difference between VR and controls in colonoscopy duration, or PDR. VR patients had numerically lower rate of post-colonoscopy adverse events than controls. The proportion of VR patients who reported resuming daily activities on the day of the procedure was significantly higher than in the control group. The VR group patients spent significantly less time in the hospital compared to the control group. CONCLUSIONS: VR technology can provide adequate substitution for sedation for most patients undergoing colonoscopy and offers comparable patient satisfaction and faster return to daily activities.

Reactive Immunomodulator Addition to Infliximab Monotherapy Restores Clinical Response in Inflammatory Bowel Disease: A Meta-Analysis.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) receiving infliximab (IFX) commonly experience immunogenic loss of response (LOR) by formation of anti-drug antibodies (ADAs). An immunomodulator (IMM) used in combination with initial IFX induction is known to reduce ADA development and improve clinical outcomes. We aimed to assess the impact of reactively adding an IMM to patients on IFX monotherapy. METHODS: We conducted a retrospective cohort study and systematic review with meta-analysis of patients with IBD demonstrating immunologic LOR, with or without clinical LOR, that had an IMM (azathioprine, 6-mercaptopurine, or methotrexate) reactively added (reactive combination therapy; rCT) to combat elevated ADAs and raise IFX level. Data were extracted for pooled effect size estimation using random-effects models, and ADA and IFX trough levels were compared pre- and post-IMM initiation. RESULTS: We identified 6 patients who received rCT due to rising ADA titers and low IFX levels. Median ADA titer decreased from 506 ng/mL (interquartile range (IQR) [416-750]) to 76.5 ng/mL (IQR [25.8-232]), an 85% decrease (p = 0.031). Median IFX trough increased from 0.4 µg/mL (IQR [0.4-0.48]) to 8.25 µg/mL (IQR [3.7-9.6]), a 20.6-fold increase (p = 0.038). Meta-analysis pooled effect size of 7 studies with 89 patients showed an 87% ADA titer reduction [95% confidence interval (CI) = 72-94%], 6.7-fold increased IFX trough (95% CI = 2.4-18.7), and 76% clinical remission rescue rate (95% CI = 59-93%). CONCLUSIONS: These results suggest rCT is a valid rescue strategy in patients with immunogenic LOR to IFX to reduce ADA titers, restore therapeutic IFX levels, and recapture clinical remission of IBD.

Diet-omics in the Study of Urban and Rural Crohn disease Evolution (SOURCE) cohort.

Crohn disease (CD) burden has increased with globalization/urbanization, and the rapid rise is attributed to environmental changes rather than genetic drift. The Study Of Urban and Rural CD Evolution (SOURCE, n = 380) has considered diet-omics domains simultaneously to detect complex interactions and identify potential beneficial and pathogenic factors linked with rural-urban transition and CD. We characterize exposures, diet, ileal transcriptomics, metabolomics, and microbiome in newly diagnosed CD patients and controls in rural and urban China and Israel. We show that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which mirror those seen in CD. Ileal transcriptomics highlights personal metabolic and immune gene expression modules, that are directly linked to potential protective dietary exposures (coffee, manganese, vitamin D), fecal metabolites, and the microbiome. Bacteria-associated metabolites are primarily linked with host immune modules, whereas diet-linked metabolites are associated with host epithelial metabolic functions.

Pan-enteric Crohn's capsule (Eliakim) score reliability and responsiveness to change in active Crohn's disease.

BACKGROUND AND AIMS: Pan-enteric capsule endoscopy (PillCam Crohn's capsule [PCC]) is a useful tool in diagnosing and monitoring Crohn's disease (CD). Eliakim score [ES] reliability and strong correlation to Lewis score (LS) and inflammatory biomarkers have been previously demonstrated using PCC in quiescent CD. We aimed to examine ES performance in active CD and its responsiveness to clinical/biochemical change over time. METHODS: Patients with CD who have started biologics were included, and were prospectively followed with clinical visits, biomarkers, and PCC at baseline, after 14 and 52 weeks. Crohn's disease activity index (CDAI), C-reactive protein (CRP) and fecal-calprotectin (FC) levels were collected, and LS and ES were calculated (independently reviewed by two experienced readers). Inter-class classification (ICC), Spearman's baseline correlation, and repeated-measures correlation (RMC) analyses were performed. RESULTS: 74 patients were included (age: 30.5 [23.3-45.0] years-old, male-50%). 142 PCCs were read (baseline-62, week-14-58, week-52-22). Inter-rater agreement was high for both LS and ES (ICC: 0.872 [p<0.001] and 0.925 [<0.001], respectively). Baseline correlations between FC&ES (r=0.509 [p<0.001]) and FC&LS (r=0.467 [p<0.001]) were comparable (p=0.56). RMC between the inflammatory biomarkers and ES were higher than between the former and LS (Reader-1: CRP- r=0.306 vs. r=0.138 [p=0.057], FC- r=0.479 vs. r=0.297 [p=0.034]; Reader-2 CRP- r=0.376 vs. r=0.204 [p=0.035], FC- r=0.549 vs. r=0.412 [p=0.075]). Moreover, ES was better correlated to CDAI than LS (p=0.036). CONCLUSIONS: ES is a reliable scoring system in assessing pan-enteric mucosal inflammation in active CD, and might have a better responsiveness to clinical/biochemical change over time compared to LS.

Ecogastroenterology: cultivating sustainable clinical excellence in an environmentally conscious landscape.

Gastrointestinal practices, especially endoscopy, have a substantial environmental impact, marked by notable greenhouse gas emissions and waste generation. As the world struggles with climate change, there emerges a pressing need to re-evaluate and reform the environmental footprint within gastrointestinal medicine. The challenge lies in finding a harmonious balance between ensuring clinical effectiveness and upholding environmental responsibility. This task involves recognising that the most significant reduction in the carbon footprint of endoscopy is achieved by avoiding unnecessary procedures; addressing the use of single-use endoscopes and accessories; and extending beyond the procedural suites to include clinics, virtual care, and conferences, among other aspects of gastrointestinal practice. The emerging digital realm in health care is crucial, given the potential environmental advantages of virtual gastroenterological care. Through an in-depth analysis, this review presents a path towards sustainable gastrointestinal practices, emphasising integrated strategies that prioritise both patient care and environmental stewardship.

A Gastroenterologist's guide to drug interactions of small molecules for inflammatory bowel disease.

Small molecule drugs are becoming increasingly used in the treatment of inflammatory bowel diseases (IBD). However, unlike monoclonal antibody drugs, which have few interactions with other medications, the pharmacokinetics of small molecule drugs are complex and may be influenced by a myriad of drug-drug interactions (DDI) as well as by patient characteristics and food intake. This review aims to provide a concise practical guide to small molecule drug interactions for the use of IBD physicians. It starts with a brief overview of the main metabolizing enzymes and transporters involved in drug interactions and the Food and Drug Administration's (FDA) approach to determining drug-interaction hazard thresholds. It is then followed by a more detailed review of the pharmacokinetics of five novel small molecules approved in IBD: Tofacitinib, Upadacitinib, Filgotinib, Ozanimod, and Etrasimod, including their known interactions and specific warnings. This review will also inform readers on challenges in determining the actual magnitude of interactions and their clinical relevance, including the arbitrary nature of some hazard thresholds, the inference of the impact on metabolizing enzymes and transporters from single-drug assays which may not reflect poly-pharmaceutical regimens, and other challenges in this field which the IBD physician needs to be cognizant of. In practice, before administering a small molecule drug, it is advisable to evaluate any potential interactions with other medications the patient is receiving. An increased awareness by health care professionals and patients, may reduce the possible risks associated with DDI of small molecule IBD drugs.

Switching from intravenous to subcutaneous infliximab maintenance therapy in inflammatory bowel disease: Post hoc longitudinal analysis of a randomized trial.

BACKGROUND: Pharmacokinetic non-inferiority of subcutaneous (SC) to intravenous (IV) CT-P13 maintenance therapy was demonstrated in a randomized trial (NCT02883452). This post hoc analysis evaluated longitudinal clinical outcomes with the two infliximab treatment strategies. METHODS: Patients with Crohn's disease or ulcerative colitis received CT­P13 IV loading doses (5 mg/kg; Week [W] 0 and W2) before randomization (1:1) to receive CT-P13 SC (body weight-based dosing every 2 weeks [Q2W]; W6-54; 'SC maintenance group') or CT­P13 IV (5 mg/kg Q8W; W6-22) then CT-P13 SC (Q2W; W30-54; 'IV-to-SC switch group'). Paired W30/W54 patient-level data were analyzed. RESULTS: Fifty-three (IV-to-SC switch) and fifty-nine (SC maintenance) patients were analyzed. Median trough serum CT-P13 concentrations were significantly higher at W54 versus W30 in the IV-to-SC switch group (20.4 versus 2.3 µg/mL; p < 0.00001), while remaining consistent in the SC maintenance group. Statistically significant improvements in pharmacokinetics, efficacy, fecal calprotectin levels, and quality of life were seen following switch to SC administration at W30 in the IV-to-SC switch group; safety findings were similar pre- and post-switch. CONCLUSION: Formulation switching from IV to SC infliximab maintenance therapy was well tolerated and may provide additional clinical improvements. Findings require confirmation in larger prospective studies.

Early Initiation of Biologics and Disease Outcomes in Adults and Children With Inflammatory Bowel Diseases: Results From the Epidemiology Group of the Nationwide Israeli Inflammatory Bowel Disease Research Nucleus Cohort.

BACKGROUND & AIMS: In this nationwide study, we explored whether early initiation of biologics is associated with improved outcomes in children and adults with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: All patients diagnosed with CD or UC in Israel (2005-2020) were included in the Epidemiology Group of the Israeli Inflammatory Bowel Disease Research Nucleus cohort, encompassing 98% of the population. We compared disease duration at biologics initiation (ie, 0-3 months, >3-12 months, >1-2 years, and >2-3 years) using the cloning, censoring, and weighting by inverse probabilities method to emulate a target trial, adjusting for time-varying confounders and selection bias. RESULTS: Of the 34,375 included patients (of whom 5240 [15%] were children), 7452 of 19,264 (39%) with CD and 2235 of 15,111 (15%) with UC received biologics. In CD, by 10 years postdiagnosis, the probability of CD-related surgery decreased gradually but modestly with earlier initiation of biologics; a significant difference was noted between >2-3 years (31%) and 0-3 months (18%; P = .02; number needed to treat, 7.7), whereas there was no difference between the 0-3-month and >3-12-month periods. The 10-year probability of steroid dependency for the 0-3-month period (19%) differed both from the >2-3-year (31%; P < .001) and 1-2-year periods (37%; P < .001). In UC, no significant differences in colectomy or steroid dependency rates were observed between the treatment initiation periods. Similar trends were noted in the pediatric population. CONCLUSIONS: Very early initiation of biologics was not associated with some outcomes except for a modest risk reduction of surgery and steroid dependency for CD, which requires confirmation in future studies. In UC, early introduction of biologics was not associated with reduced risk of colectomy or steroid dependency.

Curcumin-QingDai Combination for Patients With Active Ulcerative Colitis: A Randomized, Double-Blinded, Placebo-Controlled Trial.

BACKGROUND & AIMS: We evaluated the efficacy of herbal combination of curcumin-QingDai (CurQD) in active ulcerative colitis (UC). METHODS: Part I was an open-label trial of CurQD in patients with active UC, defined by a Simple Clinical Colitis Activity Index score of 5 or higher and a Mayo endoscopic subscore of 2 or higher. Part II was a placebo-controlled trial conducted in Israel and Greece, randomizing active UC patients at a 2:1 ratio to enteric-coated CurQD 3 g/d or placebo for 8 weeks. The co-primary outcome was clinical response (reduction in the Simple Clinical Colitis Activity Index of ≥3 points) and an objective response (Mayo endoscopic subscore improvement of ≥1 or a 50% fecal calprotectin reduction). Responding patients continued either maintenance curcumin or placebo alone for an additional 8 weeks. Aryl-hydrocarbon receptor activation was assessed by cytochrome P450 1A1 (CYP1A1) mucosal expression. RESULTS: In part I, 7 of 10 patients responded and 3 of 10 achieved clinical remission. Of 42 patients in part II, the week 8 co-primary outcome was achieved in 43% and 8% of CurQD and placebo patients, respectively (P = .033). Clinical response was observed in 85.7% vs 30.7% (P < .001), clinical remission in 14 of 28 (50%) vs 1 of 13 (8%; P = .01), a 50% calprotectin reduction in 46.4% vs 15.4% (P = .08), and endoscopic improvement in 75% vs 20% (P = .036) in the CurQD and placebo groups, respectively. Adverse events were comparable between groups. By week 16, curcumin-maintained clinical response, clinical remission, and clinical biomarker response rates were 93%, 80%, and 40%, respectively. CurQD uniquely up-regulated mucosal CYP1A1 expression, which was not observed among patients receiving placebo, mesalamine, or biologics. CONCLUSIONS: In this placebo-controlled trial, CurQD was effective for inducing response and remission in active UC patients. The aryl-hydrocarbon receptor pathway may merit further study as a potential UC treatment target. CLINICALTRIALS: gov ID: NCT03720002.

Prospective Observational Evaluation of the Time-Dependency of Adalimumab Immunogenicity and Drug Concentration in Ulcerative Colitis Patients: the POETIC II Study.

BACKGROUND AND AIMS: Home self-injection of the human anti-tumour necrosis alpha [anti-TNFα] monoclonal adalimumab complicates prospective serial-sampling studies. Although a recent study examined adalimumab levels and immunogenicity in Crohn's disease [CD] patients, prospective real-world data from ulcerative colitis [UC] patients are lacking. METHODS: A three-monthly home-visit programme from induction was established prospectively for UC patients. Clinical scores were determined at each visit, and sera were obtained for assessment of drug and anti-adalimumab antibody levels. Calprotectin was measured using a smartphone-based app. This cohort was compared to a parallel prospective cohort of adalimumab-treated CD patients [POETIC1]. RESULTS: Fifty UC patients starting adalimumab [median follow-up 28 weeks] were compared to 98 adalimumab-treated CD patients [median follow-up 44 weeks]. Only 11/50 UC patients [22%] continued treatment to the end of the follow-up compared with 50/98 [51%] CD patients (odds ratio [OR] = 0.27, p = 0.001). Loss of response was significantly more common in UC patients [OR = 3.2, p = 0.001]. Seventeen patients [34%] in the UC cohort developed anti-adalimumab antibodies, 9/17 [52.9%] as early as week 2. There was no difference between patient cohorts in the overall development of anti-adalimumab antibodies [34% vs 30.6%, respectively, OR = 1.67, p = 0.67], nor was there a difference in early immunogenicity [OR = 1.39, p = 0.35]. There was no difference in low drug levels [<3 µg/mL] between the two cohorts [OR = 0.87, p = 0.83]. CONCLUSIONS: Loss of response to adalimumab therapy was significantly more common in the UC compared to the CD cohort and was driven by a higher rate of non-immunogenic, pharmacodynamic parameters.

Biologic Treatment Modification Efficacy in Concurrent Inflammatory Bowel Disease and Ankylosing Spondylitis: A Retrospective Cohort Study at a Single Tertiary Center.

BACKGROUND: The link between ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) is well-established, with concurrent prevalence estimates ranging from 5-10%. However, there are still significant gaps in our understanding, and a comprehensive treatment guideline for these co-diagnosed patients has yet to be established. Our objective was to explore patterns of treatment alterations following the diagnosis of AS in patients previously diagnosed with IBD, and vice versa. Additionally, we sought to determine how these modifications influence clinical outcomes in both conditions. METHODS: This retrospective data-based cohort study included patients with coexisting IBD and AS that were diagnosed between the years 2009-2022 and were followed by the gastroenterology and the rheumatology units of the Sheba Medical Center, Israel. The data were extracted from the electronic health record and included demographic information, medication history, treatment modification at the time of second diagnosis, and the characteristics and activity of both IBD and AS at the index time and at the 3-month mark. RESULTS: The study included a total of 68 patients, with a male predominance (40 patients, 59%). The median age was 43 years (IQR 31-55) and 78% had Crohn's disease (CD). The median duration between the diagnosis of the first disease to the second one was 4 years (IQR 1-9.5). A significant proportion of patients (85%) underwent treatment modification at their second diagnosis. Out of the total cohort, 28% initiated biological therapy, 17.6% switched their biologic regimen, and 16.2% discontinued NSAIDS. Patients who underwent biologic modifications at time of the second diagnosis (the initiation/switch/augmentation of a concurrent regimen) experienced significantly higher rates of clinical improvement in either IBD or AS at the 90-day follow-up compared to patients who did not (68% vs. 32%, p = 0.004), and biologic modification was found to be an independent predictor for clinical improvement (OR 3.69, CI 1.08-12.58, p = 0.037). CONCLUSIONS: Our findings suggest that biologic therapy modification at the time of the second diagnosis was associated with a higher rate of improvement in AS/IBD at the 90-day follow-up.

Baseline Peripheral Blood Mononuclear Cell Transcriptomics Before Ustekinumab Treatment Is Linked With Crohn's Disease Clinical Response at 1 Year.

INTRODUCTION: Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin (IL)-12 and IL-23, is used for Crohn's disease (CD), and the documented clinical remission rate after 1 year was observed in approximately 50% of patients. We aimed to identify predictors for a clinical response using peripheral blood obtained from patients with CD just before ustekinumab treatment initiation. METHODS: RNA extraction from peripheral blood mononuclear cells was followed by mRNA paired-end sequencing. Differential gene expression was performed using DESeq2. RESULTS: We processed samples from 36 adults with CD (13 men, 36%) obtained at baseline before starting ustekinumab treatment. Twenty-two of 36 (61%) were defined as responders and 14/36 (39%) as nonresponders after 1 year based on Physician Global Assessment. Differential gene expression between responders (n = 22) and nonresponders (n = 14) did not show a gene expression signature that passed false discovery rate (FDR) correction. However, the analyses identified 68 genes, including CXCL1/2/3, which were induced in nonresponders vs responders with P < 0.05 and fold change above 1.5. Functional annotation enrichments of these 68 genes using ToppGene indicated enrichment for cytokine activity (FDR = 1.98E-05), CXCR chemokine receptor binding (FDR = 2.11E-05), IL-10 signaling (FDR = 5.03E-07), genes encoding secreted soluble factors (FDR = 1.73E-05), and myeloid dendritic cells (FDR = 1.80E-08). DISCUSSION: No substantial differences were found in peripheral blood mononuclear cell transcriptomics between responders and nonresponders. However, among the nonresponders, we noted an increased inflammatory response enriched for pathways linked with cytokine activity and chemokine receptor binding and innate myeloid signature. A larger cohort is required to validate and further explore these findings.

Middle small-bowel segment Lewis score may predict long-term outcomes among patients with quiescent Crohn's disease.

Background: Video capsule endoscopy (VCE) has been proven to accurately diagnose small-bowel inflammation and predict flares among patients with quiescent Crohn's disease (CD). However, data regarding its predictive role in this population over an extended follow-up are scarce. Objectives: To predict clinical exacerbation and to assess the yield of Lewis score in identifying CD patients with future clinical exacerbation during an extended follow-up (>24 months). Design: A post hoc analysis study. Methods: Adult patients with quiescent small-bowel CD who were followed with VCE, inflammatory biomarkers and magnetic resonance enterography in a prospective study (between 2013 and 2018). We extracted extended clinical data (up to April 2022). The primary composite outcome (i.e. clinical exacerbation) was defined as intestinal surgery, endoscopic dilation, CD-related admission, corticosteroid administration, or biological/immunomodulator treatment change during follow-up. Results: Of the 61 patients in the study [median age 29 (24-37) years, male 57.4%, biologic treatment 46.7%], 18 patients met the primary outcome during an extended follow-up [median 58.0 (34.5-93.0) months]. On univariable analysis, complicated [hazard ratio (HR) 7.348, p = 0.002] and stricturing disease phenotype (HR 5.305, p = 0.001) were associated with higher risk for clinical exacerbation during follow-up. A baseline VCE middle small-bowel segment Lewis score (midLS) ⩾ 135 identified patients with future exacerbation [AUC (area under the curve) 0.767, 95% confidence interval (CI) 0.633-0.902, p = 0.001, HR 6.317, 93% negative predictive value], whereas the AUC of the conventional Lewis score was 0.734 (95% CI: 0.589-0.879, p = 0.004). Sensitivity analysis restricted to patients with either complicated (n = 34) or stricturing (n = 26) disease phenotype revealed that midLS still predicted clinical exacerbation during follow-up (AUC 0.747/0.753, respectively), in these patients. Conclusion: MidLS predicts treatment failure in quiescent CD patients (median follow-up of 5 years) independently of disease phenotype.