Introduction

Capsule colonoscopy and Pan-intestinal Capsule Endoscopy (PCE) are well-established diagnostic procedures. However, the optimal bowel preparation regimen remains undefined, with pooled adequate cleansing rates reaching only 72.5%¹. While ultra-low volume preparations (≤1L) have demonstrated efficacy in conventional colonoscopy², their effectiveness in capsule-based modalities has yet to be determined.

Aims & Methods

In this prospective, randomized, researcher-blind, single center trial, we compared the efficacy of two ultra-low volume bowel preparation regimens, 1L Polyethylene Glycol Plus Ascorbic Acid (PEG-Asc) and 1L Sodium Picossulfate with Magnesium Citrate (SPMC). Patients referred for capsule-based procedures were randomized in a 1:1 ratio to receive either PEG-Asc or SPMC. The primary endpoints were the rates of complete examinations, adequate bowel preparation, and excellent right colon cleansing.

Results

A total of 117 patients were included, referred for capsule colonoscopy due to incomplete colonoscopy (76.1%) or for PCE to assess luminal inflammation (17.9%) or anemia (6%). Overall, 61.5% were female, with a mean age of 61.3 ± 16 years. The complete examination rate was 71.8%, with no significant difference between groups (PEG-Asc 72.9% vs. SPMC 70.7%; p = 0.792). Adequate bowel preparation was achieved in 62.4% of cases, which was significantly more frequent in the PEG-Asc group (72.9%) compared to SPMC (51.7%; p = 0.018). Among complete procedures, excellent right colon cleansing was observed more often with PEG-Asc (34.1%) than with SPMC (7.3%; p = 0.003).

Conclusion

The completion and adequate preparation rates remain suboptimal in the capsule colonoscopy and PCE procedures. In this study, both ultra-low volume purgative solutions demonstrated comparable efficacy in achieving complete examinations, but the PEG-Asc resulted in significantly better overall preparation quality and superior right colon cleansing compared to SPMC. These findings suggest that PEG-Asc may be the preferred ultra-low volume regimen for optimizing bowel visualization in capsule-based examinations.

References

1. Rosa, B., Donato, H., Cúrdia Gonçalves, T., Sousa-Pinto, B. & Cotter, J. What Is the Optimal Bowel Preparation for Capsule Colonoscopy and Pan-intestinal Capsule Endoscopy? A Systematic Review and Meta-Analysis. Dig. Dis. Sci. 68, 4418–4431 (2023).
2. Arieira, C. et al. Bowel cleansing efficacy for colonoscopy: prospective, randomized comparative study of same-day dosing with 1-L and 2-L PEG + ascorbate. Endosc. Int. Open 09, E1602–E1610 (2021).

Introduction

Ulcerative colitis (UC) and Crohn’s disease (CD), collectively inflammatory bowel disease (IBD), are characterized by chronic gastrointestinal tract inflammation. Recently, there has been interest in the use of selective oral tyrosine kinase 2 (TYK2) inhibitors for IBD treatment, which inhibit signalling downstream of multiple pro-inflammatory cytokines and may have an improved safety profile relative to non-specific Janus kinase (JAK) inhibition. Here, we use a transcriptomic approach to assess the involvement of TYK2-dependent signalling pathways in IBD, and how these are impacted by currently available treatments.

Aims & Methods

TYK2-dependent gene signatures were characterized using cytokine stimulation studies and co-expression analysis. Involvement of signature modules in IBD was assessed using disease model data generated from Takeda curated public datasets from 4059 biopsy samples from 2993 unique patients in 15 UC and 38 CD clinical studies, including assessments of golimumab, infliximab, ustekinumab, and vedolizumab. Pathway differential expression analysis was performed using Gene Set Enrichment Analysis (GSEA) and single-sample GSEA methods.^1,2

Results

Seven TYK2-dependent gene signature modules were defined, including two for type I interferon (IFN), three for IL-23, and two for IL-12. Type I IFN signatures were strongly enriched in both UC and CD, while enrichment of IL-23 was stronger in UC than CD, and enrichment of IL-12 was stronger in CD than UC. In each case, gene signature module enrichment was associated with greater disease severity. Pathway enrichment analysis of data from individual clinical studies demonstrated that specific type I IFN and IL-12 modules were significantly reduced, but not completely ameliorated, following treatment with golimumab, infliximab, ustekinumab, or vedolizumab. Further assessment of response to therapy in these studies showed that enrichment of type I IFN, IL-23, and IL-12 signature modules was associated with non-response to golimumab, infliximab, and vedolizumab.

Conclusion

Enrichment of TYK2-dependent gene signatures, including type I IFN, IL-23, and IL-12, is associated with both UC and CD. These TYK2-dependent enrichments are not fully mitigated through currently available treatments, and may be associated with non-response to treatment. It is important that all three signalling pathways are considered in the development of future treatment options.

References

1. Barbie DA, et al. Nature 2009;462:108–12.
2. Subramanian A, et al. Proc Natl Acad Sci U S A 2005;102:15545–50.

Disclosure

IP, NS, JT, PP, HW, PT, and VA are employees and shareholders of Takeda; AND was an employee and shareholder of Takeda at the time of the analysis. SSS-O is a consultant for and shareholder of CytoReason and AS-M, RS, ND, IW, and YC are employees and shareholders of CytoReason, which has received research funding from Takeda.

Introduction

Aims & Methods

Results

Conclusion

References

Choi et al. Am J Gastroenterol, 2015
Murthy et al. Gastroenterology, 2021
Manta et al. J Crohns Colitis, 2021
Bordillon et al. Gastrointest Endosc, 2021
Mohapatra et al. Endosc Int Open, 2022
Pimentel-Nunes et al. ESGE Guidelines on ESD, Endoscopy, 2022
Akiyama et al. Journal of Clinical Gastroenterology, 2022
Gordon et al. ECCO Guidelines on IBD and Malignancies, JCC, 2022