Introduction

One-fourth of colorectal neoplasia is missed at screening colonoscopy, representing the leading cause of interval colorectal cancer (I-CRC). Colonoscopy assisted by artificial intelligence (AI) with computer-aided polyp detection (CADe) showed higher adenoma detection rate (ADR) and higher adenoma per colonoscopy compared to white light (WL) colonoscopy in randomized clinical trials (RCTs). Despite ADR is a reliable quality indicator and has been associated to the risk of I-CRC and death, an adequate ADR does not eliminate the risk of lesion miss rate since the relationship between ADR and adenoma miss rate (AMR) is only indirect.

Aims & Methods

The aim of this meta-analysis is to summarise the performance of CADe systems on miss rate of colonic lesions. PubMed/Medline, Embase and Cochrane Library were systematically searched through October 2022 by two independent reviewers (M.M. and A.F.) for tandem-design RCTs comparing miss rate of colonic lesions in CAD-first colonoscopy followed by WL colonoscopy (experimental arm) vs WL-first colonoscopy followed by CAD colonoscopy (control arm).
The primary outcomes were pooled AMR and polyp miss rate (PMR). Secondary outcomes were advanced adenoma miss rate (aAMR) and sessile serrated lesion miss rate (SMR). Lesion miss rate was defined as the number of lesions detected at second colonoscopy divided by the total number of same lesions detected at first and second colonoscopy. A random-effect model was applied for pooling results. Heterogeneity was expressed as I².

Results

Overall, 4 RCTs (1166 patients), were included in the analysis. Pooled AMR was significantly lower in the CAD-first compared to WL-first arm (131/842, 15.5% vs 300/857, 35.0%; RR, 0.45; 95% CI, 0.35-0.58; P<0.001; I²=49%). PMR was also lower in the CAD-first compared to WL-first arm (192/1198, 16.0% vs 474/1244, 38.1%; RR, 0.43; 95% CI, 0.30-0.61; P<0.001; I²=82%).
No significant difference in aAMR (2/23, 8.7% vs 5/32, 15.6%; RR, 1.28; 95% CI, 0.34-4.83; P=0.71; I²=0%) and in SMR (5/43, 11.6% vs 27/67, 40.3%; RR, 0.44; 95% CI, 0.15-1.28; P=0.13; I²=46%) were observed.

Table 1. Characteristics of the studies included in the meta-analysis.

Conclusion

According to available evidence, the use of colonoscopy assisted by AI with CADe results in a significant lower AMR and PMR, with a potential implication in reducing the incidence of I-CRC. No significant difference in aAMR and SMR has been observed, even if these results should be further confirmed in studies with larger sample sizes.

Introduction

Long-term treatment of chronic inflammation after ileal pouch-anal anastomosis (IPAA) remains difficult. While biologics are widely used, real-world data on their persistence and the factors that prompt discontinuation are scarce.

Aims & Methods

We aim to describe long‑term use of bioloics as first- and advanced-line therapies, and identify predictors of discontinuation. Patients post-IPAA were prospectively followed in a comprehensive pouch clinic at a tertiary referral center. Inclusion: patients initiating biologics for chronic pouch phenotypes, specifically chronic pouchitis and Crohn's like disease of the pouch. Exclusion: biologics initiated with an existing ileostomy or for extra-intestinal manifestations. Primary outcome: drug persistence. Treatment courses were further divided into first-line and advanced-line therapies. Clinical and endoscopic remission was assessed at 26 weeks in available patients, using the corresponding PDAI subscores. Kaplan-Meier curves, log-rank tests, and Cox models were used to analyze discontinuation-free survival. A recurrent-event Cox model assessed persistence across multiple lines of therapy.

Results

Of 186 patients post-IPAA, 38 patients (21 [55%] females, median 16.8 y post‑IPAA) initiated biologics with overall 63 treatment courses: adalimumab (33.3%), infliximab (26.9%), ustekinumab (25.4%), vedolizumab (6.3%), upadacitinib (4.8%), risankizumab and golimumab (1.6% each). Median biologics overall persistence was 686 days (IQR 210‑1,702). Most treatment courses (34/63, 54%) were discontinued, mainly for primary non‑response (41%), immunogenicity (15%), or adverse events (15%).
In first‑line biologics, 16/38 (42%) patients had persistent therapy at last follow‑up. Week‑26 clinical remission was achieved by 19/21 patients (90%) and endoscopic remission by 5/10 (50%).
Predictors of earlier discontinuation of first-line biologic were: biologics initiation ≤ 5 years post-IPAA (HR 2.46, 95 % CI: 1.13‑5.97), reuse of a biologic administered pre‑IPAA (7/7 failures; HR 3.41, 1.33‑8.76) and female sex (male sex protective; HR 0.30, 0.10‑0.92). All patients of Arab‑ethnicity (5/5, 100%) discontinued therapy (p=0.05). Concomitant antibiotics (17/38, 45%) or immunomodulators (6/38, 16%) did not affect persistence. Anti-glycan antibodies developed in 4 patients (10.8%), and all discontinued biologics. All patients with NOD2 or IRGM homozygous variants discontinued biologics as well.
After first‑line failure, 15/38 (39.5%) patients underwent 25 advanced‑line courses; each additional treatment line doubled the discontinuation hazard (HR 2.48, 95% CI: 1.26‑4.90), while prior therapy duration did not predict future persistence (p=0.5). Ustekinumab accounted for 12/25 courses (48%) and showed the highest persistence rate (63.6%), whereas vedolizumab (n=3), upadacitinib (n=2) and risankizumab (n=1) were universally discontinued.

Conclusion

In patients post-IPAA with phenotypes of chronic pouch inflammation, biologics achieved high short‑term efficacy, including clinical and endoscopic remission. Clinical and surgical factors independently predicted earlier treatment discontinuation. In advanced-line therapies, treatment success declined with each subsequent treatment line. Ustekinumab demonstrated the highest persistence regardless of treatment line. This raises the possibility of a valuable rescue option even after prior biologic failure. These findings call for improved approach to biologics selection in pouch-related inflammatory conditions.

Disclosure

Jacob E Ollech: Has received grant support from Pfizer, consulting fees from Takeda, and
speaker fees from Abbvie, Janssen, Pfizer, Takeda, Novartis, and Bristol Myers Squibb.
Iris Dotan: consultation fee or honorarium from: Abbott, Abbvie, Athos, Arena, Altman
Research, Cambridge Healthcare, Celltrion, Celgene/BMS, Eli-Lilly, Ferring, Falk Pharma, Food
Industries Organization, Gilead, Galapagos, Iterative Scopes, Integra Holdings, Janssen,
Neopharm, Pfizer, Rafa laboratories, Roche/Genentech, Sangamo, Sublimity, Sandoz, Takeda,
Wildbio. Grants: Altman Research, BMS, Pfizer