Introduction

In addition to colonoscopy and histology, endoscopic ultrasound (EUS) plays a pivotal role in assessing rectal cancer (T-staging). As new therapeutic options emerge, exact imaging of the tumor is essential for the primary diagnosis and the evaluation of therapeutic response. In this regard, optical coherence tomography (OCT) offers a superior axial and lateral resolution compared to conventional rectal EUS and may contribute to individualized therapeutic strategies.

Aims & Methods

Our study aimed to evaluate the imaging quality of our further refined OCT-rectoscope prototype, which integrates an extended range additional to the optimized standard mode.
We integrated a double ferrule design with a fiber optical switch into a MHz-OCT rectoscope.
The performance of this adjustable OCT-rectoscope was assessed in two human colons, post-mortem and in situ. The body donors were preserved using an ethanol-glycerol-lysoformin-based technique resulting in true-to-life tissue consistency.

Results

The extended range mode adjusted the focus depth and imaging range and ensured imaging quality despite varying colon diameters or altered total wall thickness. The optimized standard mode gave a detailed resolution of the different rectal wall layers. Compared to the former prototype MHz-OCT rectoscope and rectal EUS, the images stood out: The mucosa appeared as a broad pale gray band, exactly circumscribed by the lamina muscularis mucosae. The submucosa was visualized as an inhomogeneous, light gray broad area. Furthermore, the muscularis propria comprising the circular and longitudinal muscle layer manifested as two homogeneous dark gray bands. The serosa was displayed as a bright band.

Conclusion

The new dual-mode MHz-OCT design allows a fast change between the extended range and the optimized standard mode. The imaging quality in both modes was exceptional compared to the state of the art EUS, with clear delineation of the different rectal wall layers, providing ideal conditions for accurate staging of rectal cancer. Further imaging studies are warranted to evaluate this dual-mode MHz-OCT rectoscope in human colons in vivo. In the future, this technique could serve additionally in indications like inflammatory bowel disease to quantify inflammation more precisely. Moreover, it could be integrated into a colonoscope design to evaluate the whole colon.

References

B. Schulte*, M. Göb* et al., High-resolution rectoscopy using MHz optical coherence tomography: a step towards real time 3D endoscopy. Scientific Reports, 02/2024
AP. Singh et al., Virtual Hall sensor triggered multi-MHz endoscopic OCT imaging for stable real-time visualization. Opt express, 02/2024

Introduction

Biologic therapies such as anti-TNF-alpha agents (infliximab, adalimumab), interleukin modulators, and gut-selective integrin antagonists like vedolizumab have significantly improved outcomes in inflammatory bowel disease (IBD), leading to enduring remission, better quality of life, and reduced surgical intervention and hospitalizations. However, many patients may eventually lose response, often due to factors like the formation of anti-drug antibodies, altered drug metabolism, or individual patient characteristics. Dose escalation—by increasing dosage or reducing intervals—is commonly used to counteract this loss, especially for anti-TNF therapies guided by therapeutic drug monitoring. Vedolizumab poses a greater challenge in this regard due to the lack of standardized monitoring protocols. We aimed to investigate the effectiveness of dose-escalated infliximab, adalimumab, and vedolizumab in IBD patients who worsened after initial response, evaluating outcomes such as treatment persistence and clinical remission, to guide more personalized, cost-effective treatment strategies.

Aims & Methods

We conducted a retrospective analysis of IBD patients who underwent Infliximab (IFX), vedolizumab, or adalimumab (ADA) therapy dose escalation between 2020-2024 at a tertiary IBD centre. Primary outcomes included clinical remission using disease activity scores (Simple Clinical Colitis Activity/SCCAI Index for UC, Harvey-Bradshaw Index/HBI for CD), biochemical markers (CRP, faecal calprotectin) and treatment persistence, evaluated at 3-12 months, 12 months, and annually up to 36 months post-escalation.

Results

A total of 155 patients (median age 31 years, 46% female) were included, of which 89 patients (57%) were prescribed dose-escalated IFX, 48 patients (31%) were prescribed dose-escalated ADA and 18 patients (12%) were prescribed dose-escalated Vedolizumab. Of those included, 118 patients (76%) had Crohn’s disease, 36 patients (23%) had ulcerative colitis (UC) and 1 patient (1%) had indeterminate disease. Indications for dose escalation included secondary loss of response (SLOR) (105/155; 68%) and/or low drug levels (65/155; 42%). Dose-escalated IFX led to significant improvements in disease activity scores at 3 months (HBI: p=0.002; SCCAI: p=0.0003). Improvement in SCCAI was maintained at 12 months (p=0.00007), 2 years (p=0.0008) and 3 years (p=0.025). Improvement in HBI was maintained at 2 years (p=0.01) and 3 years (p=0.049). Significant improvement in CRP following dose-escalated IFX was reported at 3 months (p=0.011), 12 months (p=0.004), 2 years (p=0.006) and 3 years (p=0.03). Dose-escalated ADA led to a significant improvement in HBI at 3 months (p=0.023). This improvement was maintained at 12 months (p=0.005) and 2 years (p=0.008). Early improvement in faecal calprotectin was reported at 3 months (p=0.046). Significant initial improvement in SCCAI following dose-escalated Vedolizumab was reported at 3 months (p=0.043). This improvement was not maintained at any further follow-up points (p>0.05). Minor adverse events were reported in 3 patients receiving dose escalated ADA and in 6 patients receiving dose escalated IFX.

Conclusion

Our study demonstrates that biologic dose escalation is an effective and safe mechanism to recapture clinical remission, with high rates of treatment persistence.

Introduction

Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking drug indicated for ulcerative colitis (UC), is administered intravenously at Weeks 0, 2, and 6, then every 8 weeks (Q8W). Dose escalation to every 4 weeks (Q4W) may recapture response to treatment in ~50% of patients with inadequate response. Real-world outcomes and factors associated with VDZ dose escalation from Q8W to Q4W remain underexplored.

Aims & Methods

Adults with moderate to severe UC initiating VDZ Q8W maintenance were prospectively followed in a Canadian patient support program (2015-2023). Two cohorts were included: 1) patients escalated to Q4W during maintenance after week 14 infusion (Q8W>Q4W maintenance) and 2) patients maintained on Q8W treatment for ≥2 years without escalating (Q8W maintenance). Rates of clinical remission (partial Mayo Score [PMS]<3) were described by prior biologic experience. Associations between baseline characteristics and clinical remission 3 months after Q4W dose escalation were assessed using Wilcoxon rank sum test and Fisher’s exact test. Treatment persistence at 12 and 24 months after initiation and dose escalation were evaluated in Q8W>Q4W maintenance using Kaplan-Meier survival analysis.

Results

373 patients (68% bio-naïve) and 300 patients (72% bio-naïve) were included in the Q8W>Q4W maintenance and Q8W maintenance cohorts, respectively. Median age at treatment initiation was 47 years in Q8W>Q4W maintenance and 48 years in Q8W maintenance. Both cohorts had a median baseline PMS score of 6. In Q8W>Q4W maintenance, median disease duration before treatment initiation was 4 years and median follow-up was 19 months. In Q8W maintenance, median disease and follow-up duration were 5 years and 35 months, respectively. 14 weeks post-treatment initiation, rates of remission in Q8W>Q4W maintenance were 49% (bio-naïve) and 42% (bio-experienced), and in Q8W maintenance were 72% (bio-naïve) and 70% (bio-experienced) (Table 1). Among patients in Q8W>Q4W maintenance not in remission when dose escalating, 40% achieved clinical remission 3 months after dose escalation. These patients were older at treatment initiation (49 vs. 41 years, p=0.043) and had longer disease duration (6 vs. 3 years, p=0.029) than those who did not achieve remission. In Q8W>Q4W maintenance, 12- and 24-month treatment persistence after initiation was 83% and 48% (bio-naïve) and 79% and 51% (bio-experienced), respectively. After dose escalation, 12- and 24-month treatment persistence was 48% and 39% (bio-naïve) and 53% and 45% (bio-experienced).

Conclusion

Patients with UC who underwent VDZ Q8W>Q4W dose escalation achieved lower rates of remission than those remaining on Q8W, regardless of prior bio-experience. Age at treatment initiation and disease duration were significantly associated with remission among those who escalated to Q4W.

Disclosure

JFL: AbbVie, BMS, Janssen, Frenesius-Kabi, Pfizer, Sandoz, Takeda.
EJB: Participation in advisory boards or speaker services: Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, Eli Lilly, BMS, Grant/Research: Janssen, Abbvie, Any other investment or relationship that could be judged by a reasonable and knowledgeable participant to have the potential to influence the content of the training activity, Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, BMS.
AHS: Advisory Board Membership/Consultant: Abbvie, Amgen, BioJAMP, BMS, Celltrion, Fresenius Kabi, Janssen, McKesson, Mylan Pharmaceuticals, Organon, Pendopharm, Roche, Pfizer, Sandoz, Takeda, Viatris, Speakers’ Bureau: Abbvie, Amgen, Ferring, Fresenius Kabi, Janssen, Organon, Pfizer, Sandoz, Takeda, Research Grants: Abbvie, Arena, Celgene/BMS, Genentech, Janssen, Roche, Takeda.
PW: Personal fees from AbbVie, Ferring, Biogen, and Janssen
MJA, AW, RW: were employees of Takeda Canada Inc. at the time of the study.
RM, JW, CP: were employees of Pentavere Research Group Inc. at the time of the study.
LPB: Consulting from AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HACPharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, and Vectivbio; grants from Takeda, Fresenius Kabi, and Celltrion; and lecture fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, and Medac.
BB: Advisor/Speaker: Ferring, Janssen, Abbvie, Takeda, Pfizer, BMS, Merck, Sandoz, Organon, Lifelabs, Celltrion. Advisor: Alimentiv, Gilead, Iterative Health, AMT, Celgene, Merck, Amgen, Pendopharm, Eli Lilly, BMS, Fresenius Kabi, Mylan, Viatris, Bausch Health, Celltrion Healthcare, BioJamp Pharma, Eupraxia. Research support: Janssen, Abbvie, GSK, BMS, Amgen, Genentech, Merck. Stock Options: Qu Biologic.

Introduction

Systemic corticosteroids are the first-line treatment for moderate to severe immune checkpoint inhibitor-induced enterocolitis (ICIec). Infliximab (IFX) is recommended for steroid-refractory cases; however, up to 28% of patients do not respond. Repeated-dose IFX regimens may improve outcomes and reduce recurrence, but optimal management strategies remain undefined. Here, we describe a series of patients treated with dashboard-guided IFX for ICIec.

Aims & Methods

A retrospective, descriptive case series was conducted at the IBD clinic of Hospital Universitari Vall d’Hebron between January 2021 and February 2025. The study included adult patients with ICIec who received IFX guided by a pharmacokinetic (pK) model. Demographic and clinical data were collected and analyzed.

Results

The dashboard model was applied in five patients to provide additional guidance for treatment decisions. The median age was 60 years, and three patients were female. The median time between the first immunotherapy dose and development of ICIec was 14.8 weeks. Endoscopy revealed extensive disease in 60% of patients, and 40% also had upper GI involvement. At baseline, 40% had severe inflammation. Median IFX levels at weeks 1 and 2 following the first IFX dose were 23.5 µg/mL and 22.3 µg/mL, respectively. The median interval between the first and second IFX doses was 12 days. Clinical remission was achieved in 4 out of 5 patients (80%). With a median follow-up of 16.7 ± 8 weeks, 4 of 5 patients (80%) remained in clinical remission without ICIec recurrence; one patient died due to an infectious complication.

Conclusion

Dashboard-guided IFX dosing showed benefit in ICIec patients. Use of pharmacokinetic modeling may support more tailored IFX dosing strategies, potentially improving treatment outcomes in a subset of ICIec patients with severe or extensive disease. Prospective studies are needed to better define optimal treatment strategies for ICIec.

Introduction

Piecemeal endoscopic mucosal resection (pEMR) is the preferred treatment for large non-pedunculated colorectal polyps (LNPCPs)[1,2]. A major limitation of pEMR is residual or recurrent adenoma (RRA), which was reported to in 15%-30% of cases at first surveillance colonoscopy (SC1)[3], performed 3-6 months after the index procedure, but is reduced to the range of 3%-5% by applying ablative measures to the post-EMR resection margin[4].

Aims & Methods

This study aimed to evaluate the effects of late SC1 on RRA.
This is an analysis of a prospectively collected cohort of adult patients referred for pEMR at two academic centers in Israel, from 2016 to 2023. We included all patients who underwent pEMR of LNCPCs and completed SC1.
We compared outcomes between patients who completed early SC1 at 3-6 months following the index procedure with patients who completed late SC1 later than 6 months. All procedures and surveillance colonoscopies were performed by experienced endoscopists trained in pEMR using high-definition scopes. EMR was followed by thermal ablation of the entire mucosal defect margin with snare soft tip coagulation, as previously described[4].
Scar evaluation at SC1 was performed with high-definition white light and chromoendoscopy. Our primary endpoint was RRA at SC1.
Analyses were performed per lesion. We compared baseline parameters and outcome rates between groups, and performed multivariate analysis to assess the adjusted association of months to SC1 with RRA.

Results

We analyzed 516 lesions that underwent index pEMR resection and subsequent SC1. Baseline parameters and recurrence rates are presented in Table 1. The early SC1 group (n=371) underwent SC1 at a mean of 5.1 months versus a mean of 11.1 months in the late SC1 group (p<0.01; Table 1). Polyp size in the early SC1 group was significantly larger than that in the late SC1 group (mean size 35.9 mm [SD 13.9] vs. 32.1 mm [SD 12.4], p<0.01; Table 1). The distribution of lesion location, granularity differed between the groups (Table 1). However, there were no significant differences in lesion Paris classification or rates of high grade dysplasia (Table 1).
We found no statistically significant difference in the rate of recurrence at SC1 between the two groups (6.3% in the standard group versus 4.8% in the delayed group, p=0.64). Additionally, a sub-analysis comparing the early SC1 group to patients with very late SC1 (>12 months – mean time to SC1 17.9 (SD [5.4] months) and did not reveal significant difference in recurrence at SC1 (6.2% in the early SC1 vs 6.3% in the very late group, p=1).
Multivariate analysis, adjusted for lesion size, location, and high-grade dysplasia, showed that time to SC1 was not significantly associated with RRA (odds ratio 1.05, 95% confidence interval 0.98-1.13).

TABLE 1. Comparison of baseline variables and outcome between the early and late SC1.

Conclusion

Late SC1 is not associated with an increased RRA. Hence, we suggest that high-quality pEMR with margin ablation may alleviate the need for early SC1, thereby reducing healthcare and patient burdens. Further interventional studies are required.

References

[1] Ferlitsch M, Moss A, Hassan C, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2017; 49: 270–297. doi:10.1055/S-0043-102569/ID/JR15335-1/BIB
[2] Shaukat A, Kaltenbach T, Dominitz JA, et al. Endoscopic Recognition and Management Strategies for Malignant Colorectal Polyps: Recommendations of the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2020; 159: 1916-1934.e2. doi:10.1053/j.gastro.2020.08.050
[3] Belderbos TDG, Leenders M, Moons LMG, et al. Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal lesions: Systematic review and meta-analysis. Endoscopy 2014; 46: 388–400. doi:10.1055/S-0034-1364970/ID/JR910-7/BIB
[4] Klein A, Tate DJ, Jayasekeran V, et al. Thermal Ablation of Mucosal Defect Margins Reduces Adenoma Recurrence After Colonic Endoscopic Mucosal Resection. Gastroenterology 2019; 156: 604-613.e3. doi:10.1053/j.gastro.2018.10.003

Disclosure

The authors report no conflict of interests