Introduction

Inflammatory bowel disease (IBD) management faces significant care gaps, particularly in areas such as diet and mental health support. Digital health applications provide remote support to patients with IBD to improve health, however few digital applications have published evidence of efficacy.

Aims & Methods

The purpose of this randomized controlled trial (RCT) was to identify if use of the LyfeMD digital health platform results in significant changes in health behaviours among patients in remission with Crohn’s Disease (CD) and Ulcerative Colitis (UC). LyfeMD is an integrated digital and human platform designed to improve physical and mental health. Patients over the age of 18 with UC or CD in remission were recruited in Calgary, Alberta. Participants were randomly assigned to the LyfeMD intervention (n=10) or the standard care control (n=10) group. The intervention group was given access to the LyfeMD mobile app for 8 weeks and assigned a health coach. Self-reported validated measures were collected at baseline and week 8 including demographics, leisure-time physical activity (LTPA), stress score (SS), depression and anxiety risk, sleep, screen-time outside of work, and sitting time. Diet intake was collected using 2 consecutive 24-hour recalls (ASA-24) at baseline and week 12. Intake data was used to calculate the healthy eating index (HEI). Independent and paired sample t-tests were used to identify significant differences between and within groups.

Results

Twenty people were recruited for this study (N=10 per group); 65% were female, with a mean age of 45.3 years (standard deviation) [SD] =9.9). Mean body mass index was 28.1kg/m2 (7.0) and 80% of the participants had CD. After 8 weeks the intervention group showed significant improvements in risk of anxiety (mean = -1.9/21 [2.3]) screen time (mean = -7.2/168 hours/week [11.3]), sitting hours (-10.6/168 hours/week, [12.9], and overall well-being (mean = +12.5/100 [21.2]) (p<0.05). At week 12 the intervention group also showed significant improvements in both overall diet quality (mean = +12.2/100 [16.6]) and moderation scores (mean= +5.6/50 [5.0]). Between the groups we see significant differences for both sitting time and for the moderation component of the HEI (p<0.05).

Conclusion

The LyfeMD digital health platform is a safe option for patients with IBD, providing accessible lifestyle therapy thus, reducing current gaps in the healthcare system. Future studies should focus on an increased sample size and targeting remote populations where this program may be even more valuable to healthcare providers and patients.

Disclosure

Lorian Taylor, Puneeta Tandon and Maitreyi Raman are cofounders of LyfeMD. Vidya Rajagopalan at the time of this study worked for the University of Calgary and presently works for LyfeMD.

Introduction

Patients with inflammatory bowel disease (IBD) have increasedrisk to develop bacterial enteric infections (Clostridium difficile infection [CDI] and non-CDI). Thus, when hospitalized due to IBD flare, they often undergo assessment for enteric infection. Our study aimed to assess the impact of enteric infections on hospitalized patients with IBD on the disease course, morbidity, and mortality.

Aims & Methods

In our retrospective study, we included patients hospitalized due to IBD exacerbation who were further stratified in those with enteric infection (Clostridium difficile infection (CDI) and non-CDI) and those without infections. We collected demographic and clinical data including disease location and behavior, previous treatments and surgery, comorbidities, medications for IBD, symptoms at the time of admission at the emergency department (ED), number and type of blood and stool tests for enteric infections, CRP levels, therapies during hospitalization and after discharge, post discharge related hospitalization, post discharge surgery, post discharge mortality. Continuous variables are reported as median and IQR (interquartile range [25th percentile, 75th percentile]) while categorical ones as counts and percents. Similarity between distributions is tested using the Kolmogorov-Smirnov test. Pearson’s Chi Squared (with Yate’s continuity correction) and Fisher’s exact test are used for categorical variables, while Wilcoxon rank sum test (with continuity correction) it is used for continuous ones. Statistical analysis was performed using R (v. 4.2.2 - 2022).

Results

We included 267 patients hospitalized due to IBD exacerbation with a concomitant enteric infections and 89 IBD patients without. At baseline characteristics, IBD patients with enteric infections had longer median times of hospitalization than those without (10vs 6 days, p<0.001), and they presented higher CRP levels (36 vs 17, p<0.001). Post-discharge, 29/89 (32.6%) and 57/267 (21.3%) of patients with and without enteric infections, respectively, were readmitted to ED for a flare (p=0.04). Moreover, infected patients had higher steroid dependency after discharge (p=0.003) compared to those without enteric infection. Post-discharge, we did not find any difference in biological therapy optimization between the two groups (p=0.07). We then stratified IBD patients with infections in two sub-groups: patients with CDI (n=19) and patients with non-CDI (n=70). We found a statistically significant difference in IBD related re-hospitalization between the two groups (0% in CDI vs 22.9% in non-CDI, p=0.02).

Conclusion

Our findings suggest that enteric infections in IBD patients play an important role on complications like hospitalization and steroid dependency. Early detection, appropriate management, and prevention strategies are crucial to avoid their deleterious outcomes.

Disclosure

none

Introduction

Children with inflammatory bowel diseases (IBD) are particularly vulnerable to Clostridioides difficile infections (CDI) and experience significantly worse health outcomes including increased hospitalisation and shorter time to their first bowel resection. Previous studies have correlated these outcomes to specific gastrointestinal microbiome features. However, data regarding features that may predispose PIBD patients to CDI is lacking. Furthermore, it is not known whether CDI has long-term impacts on the microbiome of PIBD patients in remission.

Aims & Methods

Our primary aims were to investigate whether PIBD-CDI patients had a distinct microbiota at baseline compared to PIBD controls, to examine whether PIBD-CDI patients had a distinct microbiome during remission than those without CDI, and whether there were changes in their stool short chain fatty acids (SCFA) composition. Finally, we aimed to assess whether PIBD patients with CDI had worse outcome.
Patients aged 2-17 years and newly diagnosed with IBD between November 2014 and March 2019 were invited to participate. Each patient was requested to submit 4 stool samples in an interval of six months between samples and follow up continued until June 2021. Patients were divided into those that developed CDI (IBD-CDI) and those who did not (IBD controls). DNA was extracted from stool samples and the microbiota of each was profiled using 16S rRNA amplicon sequencing on an Illumina MiSeq. SCFA were quantified from the stool samples. Data analysis was further divided into 2 cohorts: Cohort 1 represented microbiome data from samples of patients who developed CDI and were collected prior to the infection. Cohort 2 represented microbiome data from samples of patients in remission who had CDI. Microbial composition and SCFAs were compared to non-CDI controls within each cohort. Hazard ratio (HR) was calculated to progression to biologic treatment and surgeries in patients who had a CDI compares to those who did not. Random forest classification model was used to predict CDI using microbial composition.

Results

Patients who had CDI were more likely to progress to a biologic therapy (HR 1.85 P =0.06) and had significantly more hospitalisations (RR 2.20, P< 0.001) and surgery (HR 3.15, P= 0.019).
Cohort 1:
Patients who did not develop CDI had higher abundance of Bifidobacterium bifidum, Blautia hydrogenotrophica, Clostridium sensu stricto 2 cadaveris, Eubacterium, Ruminococcus torques group, and Lachnoclostridium.
The Eubacterium, Blautia hydrogenotrophica, Ruminococcus torques group and Lachnoclostridium were associated with high levels of stool SCFAs.
Random forest classification model was able to predict patient who did not develop CDI.
Cohort 2:
Patients post CDI had significantly lower beta diversity.
The Oscillospirales CAG 352, NK4A214 group and UCG 002 were all less abundant in post-CDI patients, and were associated with higher SCFA production. Specifically, propionic acid (CAG 352), isovaleric and isobutyric acid (NK4A214 and UCG 002). Additionally, alistipes was associated with higher levels of isovaleric and isobutyric acids.

Conclusion

We were able to predict paediatric IBD patients that were protected from CDI based on baseline microbial composition. Paediatric IBD patients who developed CDI during the course of the disease developed more severe outcome with more surgeries and hospitalisations. They had long term changes to their microbiome.

References

Pascarella F, Martinelli M, Miele E, Del Pezzo M, Roscetto E, Staiano A. Impact of Clostridium difficile infection on pediatric inflammatory bowel disease. J Pediatr. 2009 Jun;154(6):854–8.
Hellmann J, Andersen H, Fei L, Linn A, Bezold R, Lake K, et al. Microbial shifts and shorter time to bowel resection surgery associated with c. difficile in pediatric Crohn’s disease. Inflamm Bowel Dis. 2020;
Sokol H, Jegou S, McQuitty C, Straub M, Leducq V, Landman C, et al. Specificities of the intestinal microbiota in patients with inflammatory bowel disease and Clostridium difficile infection. Gut Microbes. 2018;

Disclosure

No conflict of interest

Introduction

Crohn's disease (CD) is a chronic inflammatory bowel disease that is characterized by periods of active inflammation followed by periods of remission. Current Methods for defining Crohn's disease activity are limited by various factors including low specificity, bias, invasiveness, high costs, radiation exposure and patient preference. Therefore, an easy, noninvasive, inexpensive, user-friendly, and repeatable method for the assessment of disease activity is warranted. Abnormal body temperature is a natural indicator of illness. Infrared thermography (IRT) can map body surface temperature remotely. With the advent of modern infrared cameras, data acquisition, and processing techniques, it is now possible to have real-time high-resolution thermographic images. Inflamed bowel loops are hyper-vascular and hyperemic, as detected by high doppler signs of intestinal ultrasound and bowel wall contrast enhancement in MRE, and therefore can be detected using IRT.

Aims & Methods

Our aim was to examine thermal imaging using IRT as a noninvasive tool for detecting bowel wall inflammation and disease activity in Crohn's disease patients.
The design of the study was prospective non -interventional. Consecutive adult CD patients referred for an intestinal ultrasound (IUS) exam were included, and adult healthy volunteers were recruited from the general population. Thermal images were captured using a FLIR ONE thermal camera device (FLIR Systems, Inc. Wilsonville, OR, USA) that connects directly to smartphones and utilizes a frame rate frequency of 8.7 Hz, an object temperature range of -20°C to 120°C and thermal sensitivity of 100 mK . Disease activity was defined using IUS. Thermal images of the study population were processed and compared to the results of IUS in all participants. Our novel thermal image processing algorithms extracted texture and shape features of temperature distribution across the skin covering the region of interest (ROI).

Results

The study cohort included 147 CD patients and 14 healthy volunteers. Using IUS, disease activity was found in 100 CD patients (68%). All 14 healthy volunteers had a normal IUS. The average abdominal temperature measured in the Crohn's patients (both active and inactive) was significantly higher than that of the healthy volunteers (30.4⁰±2.9⁰ C vs. 28⁰±2.9⁰ C, p=0.0032). The average abdominal temperature measured in the Crohn's group with the active disease was also found to be significantly higher than that of the healthy volunteers (30.4±2.99 C vs. 28⁰±2.9⁰ C, p=0.0035). To differentiate between active CD and CD in remission, a new parameter was defined and extracted: the fractal dimension of gradient magnitude (FDGM). The mean FDGM was significantly higher in patients with active disease than in patients with normal IUS (1.66 vs 1.63, p=0.045).

Conclusion

We describe a novel easy-to-use tool for monitoring disease activity in CD. This new method can potentially be used by patients at home as well as an office-based exam that allows precise disease follow-up and disease activity monitoring.

Disclosure

Dan Carter: Consulting fees from Takeda, Abbvie, Taro, and Lapidot; speaker fees and/or research support from Takeda, Abbvie, Janssen, and Lapidot.

Introduction

Endoscopic scoring systems like Mayo endoscopic score (MES) is the gold standard for the assessment of disease activity in patients with ulcerative colitis. Intestinal ultrasound (IUS) is an attractive tool for assessing Ulcerative colitis (UC) disease activity. A novel IUS Score for UC was proposed by us in 2019 using simple IUS parameters which correlated well with MES.

Aims & Methods

Aims: We aim to internally validate our Intestinal UltraSound – Colitis Severity Index (IUS-CSI) scoring system.
Methods: Consecutive patients with UC undergoing colonoscopy for diagnosis, screening, or flare of symptoms were included in the study. These patients were evaluated with IUS within 1 week of their colonoscopy. The colon was divided into segments – sigmoid, left, transverse, and right colon. Rectum was excluded from the study. Endoscopic disease activity was graded using MES for each colonic segment. IUS-CSI score was calculated for each colonic segment using Bowel wall thickness (BWT), Colour doppler signal score (CDS) and bowel wall stratification (BWS). The correlation of IUS-CSI with MES for that segment was studied.

Results

45 consecutive patients with UC who underwent colonoscopy were included in the study. IUS was performed in 42 patients; 3 patients could not be evaluated in view of thick abdominal wall. Total of 168 colonic segments were assessed both by colonoscopy and IUS. 32 colonic segments had MES 0, 28 segments had MES 1, 92 segments had MES 2 and 16 segments had MES 3.
Mean BWT for MES 0, 1, 2 and 3 were 2.1mm, 2.5mm, 3.4mm and 5.1mm respectively. Of all the IUS parameters, BWT and CDS had consistent correlation with MES (p=<0.001).
The IUS-CSI was calculated for each colonic segment and correlated with the MES for that segment. A linear positive correlation was seen between IUS-CSI & MES for each colonic segment using Pearson’s correlation coefficient (r) and is as follows: Sigmoid colon r= 0.88(0.79,0.93), left colon r= 0.85(0.74,0.92), transverse colon r=0.89(0.8,0.94) and right colon r=0.79(0.64,0.88). The IUS-CSI for sigmoid colon correlated with the overall MES (r =0.83; p = 0.0001).

Conclusion

IUS-CSI has an excellent correlation with MES. IUS-CSI assessment of the sigmoid colon correlates best with overall endoscopic activity.
IUS-CSI scoring system with intestinal ultrasound can be used to assess disease activity in UC non-invasively.

References

P Kakkadasam Ramaswamy, A Yelsangikar, K V Nagarajan, A Nagar, N Bhat, P154 Development of a novel ultrasound based score for assessing disease activity in ulcerative colitis: preliminary results, Journal of Crohn's and Colitis, Volume 13, Issue Supplement_1, March 2019, Page S166, https://doi.org/10.1093/ecco-jcc/jjy222.278

Introduction

Transcriptomic analysis has potential to evaluate the molecular basis and pathophysiology of inflammatory bowel disease (IBD), discover therapeutic targets, and identify biomarkers. However, the value of this technology in clinical trials is limited by substantial methodological heterogeneity, which confounds interpretation, generalisability, and comparison of data across studies.

Aims & Methods

We conducted a 2-part study that aimed to develop recommendations for standardising transcriptomic analysis in multicentre IBD clinical trials. First, 3 public databases were searched from inception to May 2021 to identify clinical trials that included patients with IBD and transcriptomic analyses. Studies that collected blood or intestinal samples and utilised microarray, RNA sequencing, or other global RNA analysis methods were eligible. Data on study design and methodological approaches to transcriptomic research ranging from biopsy location to data analysis and reporting were extracted by 2 independent reviewers. The results of the systematic review (SR) informed the second part of the study, in which a panel of 16 IBD translational researchers participated in a modified Research and Development/University of California Los Angeles appropriateness methodology (RAM) process. A list of statements focused on topics with substantial methodological heterogeneity (Table) was developed based on the SR and panel opinion and formed the basis for creation of a formal survey. Panellists rated the appropriateness of survey statements in 2 rounds, with panel input and survey modification between rounds.

Table. Overview of RAM survey topics

Results

The SR identified 37 reports (22 abstracts; 15 manuscripts) of 22 clinical trials (13 ulcerative colitis [UC]; 6 Crohn’s disease [CD]; 3 UC and CD) that included transcriptomic analyses. The earliest report was published in 2009, with most (>75%) reports published between 2017 and 2021. Most (59%) analyses were conducted at phase 1b or 2 of clinical development. The appropriateness of 416 statements were rated by 15 panellists in the first survey. The final survey included 305 statements, of which 14 panellists rated 75% appropriate, 1% inappropriate, and 24% uncertain. In general, transcriptomic analysis for multiple research objectives using either mucosal biopsy or blood samples was considered appropriate at all phases of clinical development in patients with active disease. Validation of results with external datasets and/or orthogonal methods was considered appropriate, as was the complete reporting of individual patient metadata (ex, patient demographics, disease/treatment history, sample location, and local disease activity); the latter of which was viewed as a critical component for further analysis and utility of transcriptomic data.

Conclusion

Although inclusion of transcriptomic analysis in IBD clinical trials has increased over the past decade, persistence of existing methodologic heterogeneity will continue to limit the interpretation and generalisability of the results of this important research. This study provides an initial framework for expert recommendations to address and overcome these discrepancies and increase the value of this research in clinical development.

Disclosure

BL, EC, MIS, LS: employees of Alimentiv Inc
AS: research grants from Roche-Genentech, Abbvie, GSK, Scipher Medicine, Alimentiv Inc, Boehringer Ingelheim and Agomab (Origo Biopharma); consulting fees from Genentech, GSK, Pfizer, HotSpot Therapeutics, Alimentiv, Origo Biopharma, Thabor Therapeutics, Goodgut and Boxer Capital
BS: employee of Lilly
BV: research support from from AbbVie, Biora Therapeutics, Landos, Pfizer, Sossei Heptares and Takeda; speaker’s fees from Abbvie, Biogen, Bristol Myers Squibb, Celltrion, Chiesi, Falk, Ferring, Galapagos, Janssen, MSD, Pfizer, R-Biopharm, Takeda, Truvion and Viatris; consulting fees from Abbvie, Alimentiv, Applied Strategic, Atheneum, Biora Therapeutics, Bristol Myers Squibb, Galapagos, Guidepont, Mylan, Inotrem, Ipsos, Janssen, Pfizer, Progenity, Sandoz, Sosei Heptares, Takeda, Tillots Pharma and Viatris
DM: consulting fees from Prometheus Biosciences, Takeda, Pfizer and Prometheus Laboratories; owns stock in Prometheus Biosciences.
FR: consulting fees from Adiso, Adnovate, Agomab, Allergan, AbbVie, Arena,Astra Zeneca, Boehringer-Ingelheim, Celgene/BMS, CDISC,Celsius, Cowen,Ferring,Galapagos,Galmed,Genentech,Gilead,Gossamer,Granite,Guidepoint,Helmsley,Horizon Therapeutics,Image Analysis Limited, Index Pharma, Landos,Jannsen, Koutif, Mestag,Metacrine,Mopac,Morphic,Organovo,Origo,Pfizer,Pliant,Prometheus Biosciences,Receptos, RedX,Roche,Samsung,Sanofi,Surmodics,Surrozen,Takeda,Techlab,Teva,Theravance,Thetis,UCB,Ysios,89Bio
KA: grant support from Janssen, consulting fees from Johnson & Johnson/Janssen, Lilly, Takeda
MA: speaker/consultation fees or grants from Abbvie, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Ferring, Genentech, Gilead, IQVIA, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, and Tillots
RA: speaker/consultation fees or grants from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Celltrion, Dr Falk Pharma, Ferring, Galapagos, Gilead, InDex Pharmaceuticals, Janssen-Cilag, Kliniksa Pharmaceuticals, MSD Sharp & Dohme, Novartis, Pfizer, Roche Pharma, Samsung Bioepsis, Takeda, and Tillotts Pharma
SS: scientific advisory board fees from Pfizer, Pandion, Celgene, Lilly, Takeda, Cosmo Pharmaceuticals, Merck, Sonoma Biotherapeutics, and EcoR1; grant support from Pfizer, Amgen Takeda, and Novartis; consulting fees from Amgen, Kyverna, BMS, Merck, Third Rock, 89bio, GentiBio and Apple Tree Life Sciences
TR: research grants and/or speaker/consultation fees from Abbvie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Roche, Sandoz, Takeda, UCB and XAP therapeutics
BFG: grant/research support from AbbVie, Amgen, AstraZeneca/MedImmune, Atlantic Pharmaceuticals, Boehringer Ingelheim, Celgene, Celltech, Genentech/Hoffmann-La Roche, Gilead Sciences, GlaxoSmithKline, Janssen Research & Development, Pfizer, Receptos/Celgene International, Sanofi, Santarus, Takeda Development Center Americas, Tillotts Pharma AG, and UCB Pharma; consulting fees from Abbott/AbbVie, Akebia Therapeutics, Allergan, Amgen, Applied Molecular Transport, Aptevo Therapeutics, AstraZeneca, Atlantic Pharmaceuticals, Avir Pharma, Biogen Idec, BiomX Israel, Boehringer Ingelheim, Bristol Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring, Roche/Genentech, Galapagos, GiCare Pharma, Gilead, Gossamer Pharma, GlaxoSmithKline, Inception IBD, Johnson & Johnson/Janssen, Kyowa Hakko Kirin, Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nestle, Nextbiotix, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Receptos, Salix Pharmaceuticals, Shire, Sienna Biologics, Sigmoid Pharma, Sterna Biologicals, Synergy Pharma, Takeda, Teva Pharmaceuticals, TiGenix, Tillotts Pharma AG, UCB Pharma, Vertex Pharmaceuticals, Vivelix Pharmaceuticals, VHsquared, and Zyngenia; speakers bureau fees from Abbott/AbbVie, Johnson&Johnson/Janssen, Lilly, Takeda, Tillotts Pharma AG, and UCB Pharma; is a scientific advisory board member for Abbott/AbbVie, Allergan, Amgen, AstraZeneca, Atlantic Pharmaceuticals, Avaxia Biologics, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Centocor, Elan/Biogen, Galapagos, Genentech/Roche, Johnson & Johnson/Janssen, Merck, Nestle, Novartis, Novo Nordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharmaceuticals, Sterna Biologicals, Takeda, Teva, TiGenix, Tillotts Pharma AG, and UCB Pharma; Senior Scientific Officer of Alimentiv.
VJ: consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome, Sorriso Pharmaceuticals, Takeda, Teva, Topivert, Ventyx, and Vividion; speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen, Pfizer, Shire, Takeda, and Fresenius Kabi.
NVC: grant from R-Biopharm; personal fees from AcelaBio, Alimentiv, Pfizer, ProciseDX, Ventyx.
DA, DC, FU, LM, MN, VA, YH: none