Comparison between tofacitinib and ustekinumab as a third-line therapy in refractory ulcerative colitis: A multicenter international study.

BACKGROUND: Ustekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third-line therapies in UC patients in whom anti-TNF and vedolizumab had failed. METHODS: This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC-related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C-reactive protein, endoscopic remission, treatment withdrawal, and adverse events. RESULTS: One-hundred seventeen UC patients were included in the study and followed for a median time of 11.6 months (q1 -q3, 5.5-18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow-up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 [95% CI: 1.06-3.50] p = 0.030). Twenty-eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow-up period (log-rank test, p < 0.054). No significant differences were observed for the secondary outcomes. Six and 22 adverse events occurred in the ustekinumab and tofacitinib groups, respectively (15% vs. 31%, p = 0.11). CONCLUSIONS: Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head-to-head clinical trials are needed as to confirm these data.

Baseline Data and Measurement Instruments Reported In Observational Studies In Inflammatory Bowel Disease: Results From A Systematic Review.

BACKGROUND: Heterogeneity in demographic and outcomes data with corresponding measurement instruments (MI) creates barriers for data pooling and analysis. Several core outcome sets developed in inflammatory bowel disease (IBD) homogenise outcomes data. A parallel Minimum Data Set (MDS) for baseline characteristics is lacking. We conducted a systematic review to develop the first MDS. METHODS: A systematic review of observational studies from 3 databases (2000 to 2021). Titles and abstracts were screened; full-text articles reviewed, and data extracted by two reviewers. Baseline data were grouped into 10 domains: demographics, clinical features, disease behaviour/complications, biomarkers, endoscopy, histology, radiology, healthcare utilisation and patient-reported data. Frequency of baseline data and MI within respective domains are reported. RESULTS: From 315 included studies (600,552 subjects), most originated from Europe (196; 62%), and North America (59; 19%), and were published between 2011 and 2021 (251; 80%). The most frequent domains were demographics (311; 98.7%) and clinical (289; 91.7%); 224 (71.1%) studies reported on the triad of sex (306; 97.1%), age (289; 91.7%) and disease phenotype (231; 73.3%). Few included baseline data for radiology 19; 6%), healthcare utilisation (19; 6%) and histology (17; 5.4%). Ethnicity (19; 6%), race (17; 5.4%) and alcohol/drug consumption (6; 1.9%) were least reported demographics. From 25 MI for clinical disease activity, Harvey Bradshaw Index (n=53) and Mayo score (n=37) were most frequently used. CONCLUSIONS: Substantial variability exists in baseline population data reporting. These findings will inform a future consensus for MDS in IBD to enhance data harmonisation and credibility of real-world evidence.

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.

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.

Artificial Intelligence-Assisted Colonoscopy in Real-World Clinical Practice: A Systematic Review and Meta-Analysis.

INTRODUCTION: Artificial intelligence (AI) could minimize the operator-dependent variation in colonoscopy quality. Computer-aided detection (CADe) has improved adenoma detection rate (ADR) and adenomas per colonoscopy (APC) in randomized controlled trials. There is a need to assess the impact of CADe in real-world settings. METHODS: We searched MEDLINE, EMBASE, and Web of Science for nonrandomized real-world studies of CADe in colonoscopy. Random-effects meta-analyses were performed to examine the effect of CADe on ADR and APC. The study is registered under PROSPERO (CRD42023424037). There was no funding for this study. RESULTS: Twelve of 1,314 studies met inclusion criteria. Overall, ADR was statistically significantly higher with vs without CADe (36.3% vs 35.8%, risk ratio [RR] 1.13, 95% confidence interval [CI] 1.01-1.28). This difference remained significant in subgroup analyses evaluating 6 prospective (37.3% vs 35.2%, RR 1.15, 95% CI 1.01-1.32) but not 6 retrospective (35.7% vs 36.2%, RR 1.12, 95% CI 0.92-1.36) studies. Among 6 studies with APC data, APC rate ratio with vs without CADe was 1.12 (95% CI 0.95-1.33). In 4 studies with GI Genius (Medtronic), there was no difference in ADR with vs without CADe (RR 0.96, 95% CI 0.85-1.07). DISCUSSION: ADR, but not APC, was slightly higher with vs without CADe among all available real-world studies. This difference was attributed to the results of prospective but not retrospective studies. The discrepancies between these findings and those of randomized controlled trials call for future research on the true impact of current AI technology on colonoscopy quality and the subtleties of human-AI interactions.

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.

Jejunal Inflammation in Crohn's Disease: Comparison between Diffusion Weighted Magnetic Resonance Imaging and Video Capsule Endoscopy.

BACKGROUND: Jejunal disease is associated with worse prognosis in Crohn's disease. The added value of diffusion weighted imaging for evaluating jejunal inflammation related to Crohn's Disease is scarce. OBJECTIVES: To compare diffusion weighted imaging, video capsule endoscopy, and inflammatory biomarkers in the assessment of Crohn's disease involving the jejunum. METHODS: Crohn's disease patients in clinical remission were prospectively recruited and underwent magnetic resonance (MR)-enterography and video capsule endoscopy. C-reactive protein and fecal-calprotectin levels were obtained. MR-enterography images were evaluated for restricted diffusion, and apparent diffusion coefficient values were measured. The video capsule endoscopy-based Lewis score was calculated. Associations between diffusion weighted imaging, apparent diffusion coefficient, Lewis score, and inflammatory biomarkers were evaluated. RESULTS: The study included 51 patients, and 27/51 (52.9%) with video capsule endoscopies showed jejunal mucosal inflammation. Sensitivity and specificity of restricted diffusion for video capsule endoscopy mucosal inflammation were 59.3% and 37.5% for the first reader, and 66.7% and 37.5% for the second reader, respectively. Diffusion weighted imaging was not statistically associated with jejunal video capsule endoscopy inflammation (P = 0.813). CONCLUSIONS: Diffusion weighted imaging was not an effective test for evaluation of jejunal inflammation as seen by video capsule endoscopy in patients with quiescent Crohn's disease.

Watchful Waiting After Radiological Guided Drainage of Intra-abdominal Abscess in Patients With Crohn's Disease Might Be Associated With Increased Rates of Stoma Construction.

Background: Management of spontaneous intra-abdominal abscess (IAA) in patients with Crohn's disease (CD) with radiologically guided percutaneous drainage (PD) was debated. Methods: This is a secondary analysis from a multicenter, retrospective cohort study of all the patients with CD who underwent PD followed by surgery at 19 international tertiary centers. Results: Seventeen patients (4.8%) who did not undergo surgery after PD were compared to those who had PD followed by surgical intervention 335/352 (95.2%). Patients who had PD without surgery were those with longer disease duration, more frequently had previous surgery for CD (laparotomies/laparoscopies), enteric fistula, on steroid treatment before and continue to have it after PD. Patients who had PD without subsequent surgical resection had a higher risk of stoma construction at later stages 8/17 (47.1%) versus 90/326 (27.6%) (P < .01). Patients with PD with no subsequent surgery had numerically higher rates of abscess recurrence 5/17 (29.4%) compared to those who had PD followed by surgery 45/335 (13.4%) the difference was not statistically significant (P = .07). Conclusions: Even with the low number of patients enrolled in this study who had PD of IAA without subsequent surgery, the findings indicate a markedly worse prognosis in terms of recurrence, length of stay, readmission, and stoma construction. Watchful waiting after PD to treat patients with spontaneous IAA might be indicated in selected patients with poor health status or poor prognostic factors.

Towards AI-Augmented Clinical Decision-Making: An Examination of ChatGPT's Utility in Acute Ulcerative Colitis Presentations.

This study explores the potential of OpenAI's ChatGPT as a decision support tool for acute ulcerative colitis presentations in the setting of an emergency department. We assessed ChatGPT's performance in determining disease severity using TrueLove and Witts criteria and the necessity of hospitalization for patients with ulcerative colitis, comparing results with those of expert gastroenterologists. Of 20 cases, ChatGPT's assessments were found to be 80% consistent with gastroenterologist evaluations and indicated a high degree of reliability. This suggests that ChatGPT could provide as a clinical decision support tool in assessing acute ulcerative colitis, serving as an adjunct to clinical judgment.

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.

Where does capsule endoscopy fit in the diagnostic algorithm of small bowel intussusception?

INTRODUCTION: The investigation of small bowel (SB) intussusception is variable, reflecting the lack of existing standards. The aim of this study was to understand the role of small bowel capsule endoscopy (SBCE) to investigate this pathology. METHODOLOGY: This was a retrospective multi-centre study. Patients with intussusception on SBCE and those where SBCE was carried out due to findings of intussusception on radiological investigations were included. Relevant information was collected. RESULTS: Ninety-five patients (median age 39+/-SD19.1 years, IQR 30) were included. Radiological investigations were carried out in 71 patients (74.7%) prior to SBCE with intussusception being present in 60 patients on radiological investigations (84.5%). Thirty patients (42.2%) had intussusception on radiological investigations followed by a normal SBCE. Ten patients (14.1%) had findings of intussusception on radiological investigations, a normal SBCE and repeat radiological investigations that were also normal. Abnormal findings were noted on SBCE that could explain intussusception on imaging in (16 patients) 22.5% of patients. Five patients (5.3%) underwent radiological investigations and SBCE to investigate coeliac disease and intussusception. None had associated malignancy. Four patients (4.2%) underwent SBCE to investigate familial polyposis syndromes and went on to SB enteroscopy and surgery accordingly. Most patients (n = 14; 14.8%) with intussusception on initial SBCE (without prior radiological imaging) had suspected SB bleeding (n = 10, 10.5%). Four patients (4.2%) had additional findings of a mass on CT scan and went on to have surgery. CONCLUSION: SBCE should be used to complement radiology when investigating intussusception. It is a safe non-invasive test that will minimise unnecessary surgery. Additional radiological investigations following a negative SBCE in cases of intussusception noted on initial radiological investigations are unlikely to yield positive findings. Radiological investigations following intussusception noted on SBCE in case of patients presenting with obscure gastrointestinal bleeding, may yield additional findings.

Outcome of inflammatory bowel disease patients with prior malignancy.

Background: Inflammatory bowel disease (IBD) treatment options, such as anti-tumor necrosis factor (TNF) agents and thiopurines, are associated with an increased risk of certain malignancies. However, the management of IBD patients with prior malignancy is not well defined and the literature is scarce. The main aim of this study was to describe the outcome of IBD patients with prior malignancy, or malignancy before first exposure to IBD-related biologic or immunosuppressive treatment. Methods: The study cohort included adult IBD patients followed in a tertiary academic center, with at least one malignancy diagnosed before IBD diagnosis or before initiation of IBD-related treatment. The main outcome of interest was a relapse of the previous malignancy or development of a second malignancy. Results: Our database included 1112 patients with both IBD and malignancy. Of these, 86 (9%) who had their malignancy diagnosed before IBD-related treatment initiation were identified, while 10/86 patients (9%) were further diagnosed with a second primary malignancy. Twenty patients, (20/86, 23%) had recurrence of a previous malignancy, most commonly non-melanoma skin cancer (NMSC), found in 9/20 patients (45%). Treatment with infliximab was found to be significantly associated with recurrence of NMSC (P=0.003). Conclusions: Anti-TNF treatment may be associated with an increased risk of NMSC recurrence. This underscores the importance of rigorous dermatological follow up in IBD patients with previous NMSC treated with anti-TNFs.

Spatiotemporal analysis of small bowel capsule endoscopy videos for outcomes prediction in Crohn's disease.

Background: Deep learning techniques can accurately detect and grade inflammatory findings on images from capsule endoscopy (CE) in Crohn's disease (CD). However, the predictive utility of deep learning of CE in CD for disease outcomes has not been examined. Objectives: We aimed to develop a deep learning model that can predict the need for biological therapy based on complete CE videos of newly-diagnosed CD patients. Design: This was a retrospective cohort study. The study cohort included treatment-naïve CD patients that have performed CE (SB3, Medtronic) within 6 months of diagnosis. Complete small bowel videos were extracted using the RAPID Reader software. Methods: CE videos were scored using the Lewis score (LS). Clinical, endoscopic, and laboratory data were extracted from electronic medical records. Machine learning analysis was performed using the TimeSformer computer vision algorithm developed to capture spatiotemporal characteristics for video analysis. Results: The patient cohort included 101 patients. The median duration of follow-up was 902 (354-1626) days. Biological therapy was initiated by 37 (36.6%) out of 101 patients. TimeSformer algorithm achieved training and testing accuracy of 82% and 81%, respectively, with an Area under the ROC Curve (AUC) of 0.86 to predict the need for biological therapy. In comparison, the AUC for LS was 0.70 and for fecal calprotectin 0.74. Conclusion: Spatiotemporal analysis of complete CE videos of newly-diagnosed CD patients achieved accurate prediction of the need for biological therapy. The accuracy was superior to that of the human reader index or fecal calprotectin. Following future validation studies, this approach will allow for fast and accurate personalization of treatment decisions in CD.

Capsule Endoscopy in Inflammatory Bowel Disease: Panenteric Capsule Endoscopy and Application of Artificial Intelligence.

Video capsule endoscopy (VCE) of the small-bowel has been proven to accurately diagnose small-bowel inflammation and to predict future clinical flares among patients with Crohn's disease (CD). In 2017, the panenteric capsule (PillCam Crohn's system) was introduced for the first time, enabling a reliable evaluation of the whole small and large intestines. The great advantage of visualization of both parts of the gastrointestinal tract in a feasible and single procedure, holds a significant promise for patients with CD, enabling determination of the disease extent and severity, and potentially optimize disease management. In recent years, applications of machine learning, for VCE have been well studied, demonstrating impressive performance and high accuracy for the detection of various gastrointestinal pathologies, among them inflammatory bowel disease lesions. The use of artificial neural network models has been proven to accurately detect/classify and grade CD lesions, and shorten the VCE reading time, resulting in a less tedious process with a potential to minimize missed diagnosis and better predict clinical outcomes. Nevertheless, prospective, and real-world studies are essential to precisely examine artificial intelligence applications in real-life inflammatory bowel disease practice.

Self-reported treatment effectiveness for Crohn's disease using a novel crowdsourcing web-based platform.

BACKGROUND AND AIMS: Internet and social media platforms have become an unprecedented source for sharing self-experience, potentially allowing the collection and integration of health data with patient experience. StuffThatWorks (STW) is an online open platform that applies machine learning and the power of crowdsourcing, where patients with chronic medical conditions can self-report and compare their individual outcomes using a structured online questionnaire. We aimed to conduct a cross-sectional, international, crowdsourcing, artificial-intelligence (AI) web-based study of patients with Crohn's disease (CD) self-reporting their outcomes. METHODS: A proprietary STW Bayesian inference model was built to measure improvement in CD severity (on scale of 1-5) for each treatment and ranked treatments using effectiveness. The effectiveness of first-line biological treatments was analyzed by multiple comparisons and by calculating odds ratios and 95% confidence intervals for each treatment pair. RESULTS: We included 7593 self-reported CD patients for the analysis. Most of the participants were female (75.8%) and from English-speaking countries (95.7%). Overall, anti-TNF drugs were the most reported tried treatment (52.8%). Infliximab (IFX) was ranked as the most effective treatment by the STW effectiveness model followed by bowel surgery (second), adalimumab (ADA, third), ustekinumab (UST, 4rd), and vedolizumab (VDZ, fifth). In paired comparison analyses, IFX was most effective, ADA had similar effectiveness compared to UST and all three were more effective than VDZ. CONCLUSION: We present the first online crowdsourcing AI platform-based study of self-reported treatment effectiveness in CD. Net-based crowdsourcing patient-reported outcome platforms can potentially help both clinicians and patients select the best treatment for their condition.

Do Vedolizumab trough Levels Predict the Outcome of Subsequent Therapy in Inflammatory Bowel Disease?

Background: Vedolizumab trough serum levels have been associated with clinical and endoscopic response in patients with inflammatory bowel disease (IBD). A recent study demonstrated that higher trough levels before dose escalation are associated with favorable outcomes. Objectives: We aimed to identify whether vedolizumab trough levels predict outcome of subsequent therapy. Methods: This retrospective study included IBD patients consecutively receiving vedolizumab therapy between November 2014 and June 2021. Only patients with a loss of response (LOR) to vedolizumab and available trough drug levels prior to therapy cessation were included. Clinical and endoscopic scores were recorded at 6 and 12 months post switching therapy. Results: Overall, 86 IBD patients (51 Crohn's disease, 35 ulcerative colitis) who discontinued vedolizumab were included; of those, 72 (83.7%) were due to LOR. Upon vedolizumab discontinuation, 66.3% of patients were switched to another biologic therapy. Trough vedolizumab levels at discontinuation due to LOR did not differ between patients with clinical response and LOR regarding subsequent therapy at 6 months [median 33.8 µg/mL (IQR 13.2-51.6) versus 31.7 µg/mL (IQR 9.1-64.8), p = 0.9] and at 12 months [median 29.6 µg/mL (IQR 14.3-51.6) versus 34.1 µg/mL (IQR 12.2-64.7), p = 0.6]. Patients progressing to subsequent surgery had numerically lower vedolizumab trough levels at LOR compared with patients who were treated with an additional medical therapy (median 14.3, IQR 4-28.2 µg/mL versus 33.5, IQR 13-51.6 µg/mL, p = 0.08). Conclusions: Vedolizumab trough levels upon LOR do not predict response to subsequent medical therapy; however, lower drug levels may suggest a more aggressive disease pattern and future need for surgery.

Real-world experience with Curcumin-QingDai combination for patients with active ulcerative colitis: A retrospective multicentre cohort study.

BACKGROUND: Curcumin and QingDai (QD, Indigo) have been shown to be effective for treating active ulcerative colitis (UC). AIM: To evaluate the real-world experience with the Curcumin-QingDai (CurQD) herbal combination to induce remission in active UC. METHODS: A retrospec-tive multicentre adult cohort study from five tertiary academic centres (2018-2022). Active UC was defined as a Simple Clinical Colitis Activity Index (SCCAI) ≥ 3. Patients were induced by CurQD. The primary outcome was clinical remission at weeks 8-12, defined as SCCAI ≤2 and a decrease ≥3 points from baseline. Secondary outcomes were clinical response (SCCAI decrease ≥3 points), corticosteroid-free remission, faecal calprotectin (FC) response (reduction ≥50%), FC normalisation (FC ≤100 µg/g for patients with FC ≥300 µg/g at baseline), and safety. All outcomes were analysed for patients who were maintaining stable treatment. RESULTS: Eighty-eight patients were included; 50% were biologics/small molecules experienced, and 36.5% received ≥2 biologics/small molecules. Clinical remission was achieved in 41 (46.5%), and clinical response in 53 (60.2%). Median SCCAI decreased from 7 (IQR:5-9) to 2 (IQR:1-3); p < 0.0001. Of the 26 patients on corticosteroids at baseline, seven achieved corticosteroid-free remission. Among 43 biologics/small molecules experienced patients, clinical remission was achieved in 39.5% and clinical response in 58.1%. FC normalisation and response were achieved in 17/29 and 27/33, respectively. Median FC decreased from 1000 µg/g (IQR:392-2772) at baseline to 75 µg/g (IQR:12-136) at the end of inductions (n = 30 patients with paired samples); p < 0.0001. No overt safety signals emerged. CONCLUSION: In this real-world cohort, CurQD effectively induced clinical and biomarker remission in patients with active UC, including patients who were biologics/small molecules experienced.

Impact of Vedolizumab on Extraintestinal Manifestations in Inflammatory Bowel Disease: Results From a Descriptive, Retrospective, Real-world Study.

BACKGROUND: Patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, may develop extraintestinal manifestations (EIMs). The EMOTIVE study aimed to analyze the effect of vedolizumab on EIMs in a real-world cohort of patients with IBD. METHODS: This multicenter, descriptive, retrospective study was conducted in Belgium, Denmark, Israel, the Netherlands, and Switzerland in adults with moderately to severely active IBD and concurrent active EIMs at vedolizumab initiation (index date), with a ≥6-month follow-up after the index date. The primary endpoint was resolution of all EIMs within 6 months of vedolizumab initiation. RESULTS: In 99 eligible patients, the most frequent EIMs were arthralgia (69.7%), peripheral spondyloarthritis (21.2%), and axial spondyloarthritis (10.1%). Within 6 and 12 months of vedolizumab initiation, 19.2% and 25.3% of patients reported resolution of all EIMs, while 36.5% and 49.5% of all EIMs were reported to be improved (combination of resolution and partial response), respectively. Vedolizumab treatment persistence at 12 months was 82.8%. Adverse events were reported in 18.2% of patients, with the most frequent being arthralgia (4.0%). CONCLUSIONS: This real-world study showed resolution of all EIMs in up to one-fourth of patients with IBD and improvement in up to half of EIMs within 12 months of vedolizumab treatment. Overall, vedolizumab was effective on EIMs in patients with IBD and showed a good safety profile.