Introduction

Deficiency of serum 25-hydroxyvitamin D [25(OH)D] was associated with decreased short-term response to anti-tumor necrosis factor-alpha (TNFα) agents in adults with inflammatory bowel disease (IBD). Data on the long-term outcome of pediatric IBD with 25(OH)D deficiency under anti-TNFα therapy are scarce. The aim of this study was to evaluate the relation between serum 25(OH)D levels and the long-term outcome of pediatric IBD under anti-TNFα therapy.

Aims & Methods

Children (<18 years) with IBD that were treated with anti-TNFα agents, and had 25(OH)D levels measured at the initiation of therapy and at least 12 months of follow up under this therapy were included. Demographic, clinical and laboratory data were retrospectively collected. IBD activity was measured by Pediatric Crohn's Disease Activity Index (PCDAI) or Pediatric ulcerative colitis activity index (PUCAI). IBD outcomes were defined as clinical response (reduction of PCDAI > 12.5 or PUCAI > 20 points), clinical remission (PCDAI or PUCAI < 10 points), laboratory remission (C-reactive protein < 5 mg/L and fecal calprotectin < 150 mcg/g), IBD exacerbation (relapse of clinical symptoms accompanied with an elevation above 10 points in the PCDAI or the PUCAI), IBD-related hospitalization, surgery and durability of therapy. Vitamin D deficiency was defined as serum 25(OH)D levels < 30 ng/ml.

Results

Of 530 children with IBD, 150 were treated with anti-TNFα agents and 84 [58 Crohn's disease, 26 ulcerative colitis, median age 15.2 (12.8-16.5) years] met the inclusion criteria. Their median 25(OH)D level was 23 (16.3-29.6) ng/ml, and 65 (77.4%) were 25(OH)D-deficient. 25(OH)D levels above 30 ng/ml were significantly associated with clinical response [HR=4 (1.43-11.11), P=0.008], clinical remission [HR=4.62 (2.56-8.33), P<0.001] and laboratory remission [HR=6.34 (3.39-11.84), P<0.001). Disease exacerbation, IBD-related hospitalization and surgery were non-significantly more prevalent among 25(OH)D-deficient children (12.2% vs. 5.3%, 13.8% vs. 0, 3.1% vs. 0, respectively, P=NS). While anti-TNFα trough levels were similar between 25(OH)D-deficient and non-deficient children, intensification of anti-TNFα therapy was more prevalent among 25(OH)D-deficient children (64.6% vs. 21.1%, P<0.001), as was discontinuation of anti-TNFα therapy (32.3% vs. 10.5%, P=0.061). In a multivariate analysis that included age, sex, IBD type, disease duration and anti-TNFα trough levels, 25(OH)D levels above 30 ng/ml were significantly associated with clinical response and remission [HR=3.92 (1.52-10.08), P=0.005 and HR=5.23 (1.88-14.55), P=0.002, respectively].

Conclusion

Deficiency of serum 25(OH)D is an independent predictor to poor IBD outcome under anti-TNFα therapy in children with IBD. Prospective studies are needed to determine whether supplementation of vitamin D can improve IBD outcome under anti-TNFα therapy.

Introduction

Colon Capsule Endoscopy (CCE) offers a non-invasive alternative to colonoscopy for lower gastrointestinal (GI) investigations. However, its adoption is limited by lengthy reading times, reader fatigue, and variable diagnostic accuracy. These factors are often influenced by bowel preparation quality and completion rates. Artificial intelligence (AI) has shown the potential to improve diagnostic accuracy of polyp detection and reduce reading times in capsule endoscopy.

Aims & Methods

Objective(s): The primary aim is to assess the diagnostic accuracy of Computer-Aided Detection (CADe) system (AiSPEED™) assisted CCE reading using full-video analysis in a real-world clinical setting. Secondary outcome was to assess a) non-inferiority compared to standard clinician reading in detecting polypoid lesions and b) mean reading time.
Methods: CESCAIL study is a multi-centre study of 14 UK centres recruited 720 participants between November 2021 and September 2024. Participants (prospectively and retrospectively enrolled ) included those ≥18 years referred for CCE under the urgent cancer pathway or for post-polypectomy surveillance. CCEs were performed using PillCam™ COLON 2 and analysed using AiSPEED™. CCE videos were evaluated by separate clinicians who provided standard readings, while AI-assisted reading included an AI-assisted pre-reader review and subsequent clinician validation.

Results

720 patients were enrolled, with 673 included in the final analysis. The capsule excretion rate before battery depletion was 77.1%, with adequate bowel preparation achieved at 78.1% (with standard) and 74.0% (with AI-assisted reading) (McNemar p=0.108). In the per-patient analysis, the diagnostic yield for detecting polyps was 63.6% (428/673) for standard reading and 70.6% (475/673) for AI-assisted reading, using the expert panel as the reference standard. These findings confirmed both non-inferiority (p<0.001) and superiority (p<0.001) of the AI-assisted reading. The diagnostic accuracy for detecting polyps requiring follow-up procedure (flexible sigmoidoscopy/colonoscopy) was 0.96 (95% CI: 0.95–0.98) for AI-assisted reading, compared to 0.91 (95% CI: 0.89–0.93) for standard reading (p<0.0001) (see Table 1). The mean reading time per video was 8.7 minutes for AI-assisted reading compared to 47.3 minutes for standard reading, representing a 5.4-fold reduction.

Conclusion

AI-assisted reading with AiSPEED™ offers the potential for greater accuracy in polyp detection and significantly reduced clinician reading times during CCE examination compared to standard reading methods.

References

1. Moen S, Vuik FER, Kuipers EJ, Spaander MCW. Artificial Intelligence in Colon Capsule Endoscopy-A Systematic Review. Diagnostics (Basel). 2022;12(8).
2. Mota J, Joao Almeida M, Mendes F, Martins M, Ribeiro T, Afonso J, et al. A Comprehensive Review of Artificial Intelligence and Colon Capsule Endoscopy: Opportunities and Challenges. Diagnostics (Basel). 2024;14(18).
3. Spada C, Piccirelli S, Hassan C, Ferrari C, Toth E, Gonzalez-Suarez B, et al. AI-assisted capsule endoscopy reading in suspected small bowel bleeding: a multicentre prospective study. Lancet Digit Health. 2024;6(5):e345-e53.
4. Spada C, Hassan C, Galmiche JP, Neuhaus H, Dumonceau JM, Adler S, et al. Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2012;44(5):527-36.
5. PillCam COLON 2 for investigation of the colon through direct visualisation [Internet]. NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE. August 2024. Available from: https://www.nice.org.uk/guidance/gid-dg10083/documents/final-scope-2.

Disclosure

Hagen Wenzek serves as the CEO, and Elizabeth White is the Project Manager at Corporate Health International which owns the ​intellectual property of AiSPEED^TM

Introduction

Inflammatory cells and cytokines play an instrumental role in the pathogenesis and disease course of ulcerative colitis (UC) and are thus accepted therapeutic targets. NX-13 is a first-in-class, orally active, once-daily, gut-selective NLRX1 agonist in development for UC. NLRX1 is a mitochondrial associated protein with a novel, bimodal, immunometabolic mechanism which upregulates mitochondrial metabolism, reduces oxidative stress, and decreases pro-inflammatory cell differentiation and cytokine release broadly in mouse models of IBD¹. NX-13 was well tolerated and showed gut selectivity with low systemic drug exposure in Phase 1 studies reported previously^2,3. We now present data from the phase 1b study describing changes in tissue cytokine levels and related to clinical response.

Aims & Methods

In this double-blind phase 1B trial (NCT04862741)³, 36 patients with active UC (Total Mayo Score 4-10; Mayo endoscopic subscore 2-3) were randomly assigned to NX-13 250mg Immediate Release (IR), 500mg IR, 500mg Delayed Release (DR) or Placebo QD for 4 weeks. Protein levels of IFNγ, IL-10, IL-12(p40), IL-17, IL-4, IL-6, IL-8, MCP1, and TNFα in colonic tissue from NX-13 treated patients collected at screening (baseline) and week 4 of treatment were determined by Human Cytokine/Chemokine Panel – Immunology Multiplex Assay (Millipore Sigma) normalized to total protein concentrations. Patients from all NX-13 dose groups with paired baseline and week 4 samples (n=18) were included in this analysis. Mann-Whitney U testing was used for comparisons between responders (Resp) and non-responders (NR).

Results

Baseline cytokines levels were not different between Resp (change from baseline of at least –3, or –30% in total Mayo Score) and NR. NX-13 treatment resulted in a decrease of multiple proinflammatory cytokines at week 4 compared to baseline in most patients, and especially in Resp. compared to NR at week 4 (Table 1). Primarily, the reduction (% change from baseline) of Th1 cytokines IL-12(p40) and IFNγ was greater in NX-13 treated patients with clinical response compared to NR, resulting in significantly lower values in Resp compared to NR at the end of the 4-week study. Similarly, IL-6 also tended to be lower among Resp. after 4 weeks of treatment with NX-13. Additionally, Th2 cytokine IL-4 values were significantly lower after 4 weeks of NX-13 in patients in clinical response compared to NR. Myeloid cell recruitment may also have been affected by cytokine changes induced by NX-13 as IL-8 and MCP levels were lower in clinical Resp. Reduced myeloid cell recruitment is consistent with higher levels of histologic remission in NX-13 treated patients³.

Conclusion

Broad changes in tissue cytokine expression were specifically observed in patients that responded to NX-13- after 4 weeks of treatment, compared to non-responders. These changes mirror those seen in preclinical mouse colitis models where a broad array of cytokines is reduced¹. The early onset of cytokine shifts associated with clinical response to NX-13 at week 4 is notable and will be assessed in the ongoing phase 2 NEXUS study in patients with moderate to severe UC (NCT05785715).

References

¹Leber, et al. J Immunol 203(12); ²Leber, et al. UEGW J 9(Supp); ³Verstockt, et al. JCC epub 11NOV2023

Disclosure

BS has received grant support from Pfizer (to institution); served as a consultant (served as a representative of Charité) for AbbVie, Arena, BMS, Boehringer, Celgene, Endpoint Health, Falk, Galapagos, Janssen, Landos, Lilly, Pfizer, PredictImmune, and Takeda; and has received speaker’s fees (served as a representative of Charité) from AbbVie, CED Service GmbH, Falk, Ferring, Galapagos, Janssen, Lilly, Pfizer, and Takeda; support for attending meetings/travel from Falk; and served as president of ECCO. | SV has received grants from AbbVie, J&J, Pfizer, Takeda, and Galapagos; consulting and/or speaking fees from AbbVie, Abivax, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma AG, and Zealand Pharma. | AY reports consulting fees from Takeda, Prometheus Labs, Arena Pharmaceuticals, and Bristol Myers Squibb; and speaker bureau fees from Bristol Myers Squibb. | SS has received personal fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Dr Falk Pharma, Ferring, Fresenius, Galapagos, Genentech, GSK, Gilead, I-MAB Biopharma, Janssen, Lilly, Merck, Novartis-Sandoz, Pfizer, Protagonist, Takeda, and Theravance. | SD reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB Inc., and Vifor; he reports lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, and Takeda. | RM is an employee of Landos. | FC is an employee of Landos. | BV has received grants 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. Consultancy fees from Abbvie, Alimentiv, Applied Strategic, Atheneum, Biora Therapeutics, Bristol Myers Squibb, Galapagos, Guidepoint, Landos, Mylan, Inotrem, Ipsos, Janssen, Progenity, Sandoz, Sosei Heptares, Takeda, Tillots Pharma and Viatris. | MCD reports consulting fees from AbbVie, Arena, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech, Gilead, Janssen, Pfizer, Prometheus Labs, and Takeda; and is founder and a shareholder of Trellus Health.

Introduction

The Epi-IBD cohort is a prospective European population-based cohort of 1,390 patients diagnosed with inflammatory bowel disease (IBD) in 2010 and 2011 according to Copenhagen criteria. Of these, 482 were diagnosed with Crohn’s Disease (CD), 817 with ulcerative colitis (UC) and 91 with IBD unclassified (IBDU). The Epi-IBD cohort was established to examine differences in incidence, treatment strategies, disease course and prognosis among IBD patients in Eastern and Western Europe.

Aims & Methods

This study aims to describe the use of biological therapy as well as the treatment prior to biological therapy. IBD patients were followed prospectively from the time of diagnosis until the 31^st December 2020, death, emigration or loss of follow-up. Clinical data on surgery, hospitalizations, and medical treatment, were captured throughout the follow-up period and entered into a validated web-database, www.epi-ibd.org.

Results

During a median follow-up period of 10.7 (interquartile range (IQR), 10.0-11.4) years, 34% (N=165/482) of CD and 15% (N=122/817) of UC patients were started on biological therapy. Biological therapy was initiated within the first year after diagnosis in 16.8% (N=81/482) of all CD and 3.8% (N=31/817) of all UC patients. In median biological therapy was started at 1.0 year (IQR, 0.3-3.1) and 2.7 years (IQR, 1.6-4.0) after CD and UC diagnosis, respectively. First-line biological therapy was infliximab in 74% (N=213/287) and adalimumab in 22% (N=64/287) of the patients. The remaing (N=10/287) received either Golimumab, Vedolizumab, Ustekinumab or were part of a trial/unknown. The sequences of biological therapies are displayed in Sankey diagrams, Figures 1 and 2. Herein illustrated is that 34% (N=56/165) CD and 34% (N=41/122) UC received at least two different biological drugs. Immunomodulators were initiated simultaneously to the first biological therapy in 19% (N=31/165) of CD patients and in 9% (N=11/122) of UC patients. Overall 63% (N=104/165) CD and 51% (N=62/122) UC patients were receiving concomittant immunomodulators with the first biological therapy.
The sequences of therapy leading up to biological therapy are displayed in Sankey diagrams, Figures 3 and 4. Herein illustrated is that the most common sequence of treatment before the first biological therapy for CD was 1) Steroids, 2) Immunomodulators (21%, N=34/165), and for UC was 1) 5-aminosalicylic-acid (5ASA), 2) Steroids, 3) Immunomodulators (39%, N=48/122). Prior to the first biological therapy one, two and three or more courses of systemic steroid were used in 41%, 28% and 17% (N=67, 47 and 28) of CD patients and 43%, 24% and 26% (N=52, 29 and 32) of UC patients. In 14% (N=23/165) and 7% (N=9/122) of CD and UC patients, systemic steroids were not used prior to first biological therapy. In patients having immunomodulators prior to biological therapy, these were administered for a median of 0.5 (IQR, 0.1-1.9) years and 1.1 (IQR, 0.2-3,2) years in CD and UC, respectively. For 5ASA this was 0.8 (IQR, 0.2-1.5) years for CD and 2.2 (IQR, 0.8-4.3) years for UC.

Conclusion

In this multicenter European population-based cohort, different prescribing patterns for biologics emerge: 34% of CD and 15% of UC patients received biologics within 10 years after diagnosis. Infliximab was the most common first-line biological therapy. Only about half of the patients received concomitant immunomodulators. Prior to the first biological therapy, most patients were exposed to systemic steroids and many to repeated courses.

Introduction

‘Biologic therapies’ are the mainstay treatment for moderate to severe Inflammatory Bowel Disease (IBD), resulting in fewer hospitalisations, adequate treatment response and mucosal healing. ^[1] Adalimumab, Golimumab, Ustekinumab & Risankizumab are administered subcutaneously (SC), Infliximab and Vedolizumab are administered intravenously (IV), and have additionally been available SC since 2020. SC Infliximab was used during the pandemic to limit exposure to hospitals & reduce risk of Covid-19, ^[2] as well as for convenience.

Aims & Methods

We explore patient’s views of IV and SC administered treatments via a paper-based survey for those patients who were on IV treatment when attending for infusions, and a telephone survey on patients with IBD who have been on SC treatment.

Results

IV survey

• 122 completed the survey.
• 50/122 (41.0%) were on Vedolizumab (41.0%), 64 (52.5%) Infliximab, 8 (6.6%) others / didn’t specify.
• 25/120 (20.8%) had been on IV therapy for 2-6 months, 17 (14.2%) for 7-12 months, 29 (24.2%) for 1-3 years, 21 (17.5%) for 3-5 years, 21 (17.5%) for >5 years.
• 107/120 (89.2%) rated treatments as easy, 13 (10.8%) intermediate, 0 difficult.
• 25/112 (22.3%) were previously on SC injections. Of this group: 15/24 (60.0%) favoured the IV route, 9 (36.0%) favoured the SC route.
• 4/15 who favoured the IV route “did not like to inject themselves” or “found it difficult”. 3/15 preferred IV route as they were being monitored.
• 104/110 (94.5%) attended all scheduled blood tests, 4 (3.6%) attended most of them
• 106/109 (97.2%) attended all OP appointments, 2 (1.8%) attend most
• 91/111 (82.0%) had no concerns, 10 (9.0%) had concerns over side effects (SE)
• 31/104 (29.8%) reported SE.
• 6/29 (20.7%) stated SE not affected their quality of life (QoL), 12 (41.4%) little impact QoL, 10 (34.5%) moderate impact, 1 (3.4%) severe impact.
• 96/105 (91.4%) would recommend IV route

• 106/113 (93.8%) completed the survey..
• 54/106 patients were on Adalimumab (50.9%), 24 (22.6%) Ustekinumab, 13 (12.2%) Vedolizumab , 13 (12.3%) Infliximab, 2 (1.9%) Golimumab
• 10/106 (9.4%) for 1-6 months, 21 (19.8%) for 6-12 months, 33 (31.1%) for 1-3yrs, 21 (19.8%) for 3-5 years and 20 (18.9%) for >5 years.
• 89/106 (83.9%) rated treatment administration as easy, 10 (9.4%) intermediate, 2 (1.9%) difficult
• 59/106 (55.7%) were previously on IV infusions. Of this group: 43/59 (72.9%) favoured the SC route, 8 (13.6%) favoured IV, and 8 (13.6%) no preference.
• 24/43 who favoured who favoured SC route stated ‘convenient”, “easy”, “not have to attend hospital” as reasons.
• 86/106 (81.1%) attended all scheduled blood tests, 5 (4.7%) attended most of them,
• 102/106 (96.2%) attended all OP appointments, 3 (2.8%) attend most,
• 68/106 (64.2%) had no concerns, 21 (19.81%) concerned about fewer face to face episodes
• 40/106 (37.7%) reported SE. 8 (20%) skin reactions
• 11/40 (27.5%) stated SE not affected their quality of life (QoL), 14 (35%) little impact QoL, 9 (22.5%) moderate impact, 6 (15%) severe impact.
• 87/106 (82.1%) recommend SC route

Conclusion

The survey found that both IV and SC treatments were easy to administer for the vast majority (89.2% & 84.9%), For patients on SC therapy who previously had IV infusions, 75.6% preferred SC as “convenient”, “easy” and “no (need to attend) hospital”. For patients on IV therapy who previously had SC, 60.0% preferred IV as “did not ned to self inject / found it difficult”, and “preferred monitoring”. Overall there are high levels of satisfaction with 91.4% of patients on IV treatment, and 82.1% of patients on SC treatment recommend their current route of administration.

References

1. E J Mao, G S Hazlewood, G G Kaplan, L Peyrin-Biroulet, and A N Ananthakrishnan, Systematic review with meta-analysis: comparative efficacy of immunosuppressants and biologics for reducing hospitalisation and surgery in Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther, 45: 3-13. https://doi.org/10.1111/apt.13847
2. P J Smith, L Critchley, D Storey, et al, Efficacy and Safety of Elective Switching from Intravenous to Subcutaneous Infliximab [CT-P13]: A Multicentre Cohort Study, Journal of Crohn's and Colitis, Volume 16, Issue 9, September 2022, Pages 1436-46. https://doi.org/10.1093/ecco-jcc/jjac053