Introduction

Placebo and treatment response rates in randomized ulcerative colitis (UC) trials impact clinical trial design and patients required to demonstrate efficacy. Prior efforts to predict endoscopic healing (EH) in UC trial patients using clinical measures have failed to produce meaningful predictive power. Using AI analysis of baseline endoscopy videos from the ustekinumab UNIFI registration Phase 3 trial in moderate to severe UC, we demonstrate robust accuracy to predict 8 week endoscopic healing in ulcerative colitis patients treated with placebo or drug.

Aims & Methods

300 screening endoscopy videos were obtained from UC patients receiving placebo, and 606 screening endoscopy videos were obtained from UC patients receiving ustekinumab (130mg or 6mg/kg) in the UNIFI induction trial. For all videos, visual features were extracted using EndoDINO, an AI foundation model pre-trained on the largest reported endoscopy video dataset. For each patient, 21 baseline clinical measures were also obtained as predictors. These included fecal calprotectin, albumin, C-reactive protein, lactoferrin, Geboes grading, prior biologics failure, prior steroids failure, UCEIS scores, and Mayo scores.
For each of the placebo and drug arms, we trained two binary classification models: one using the AI visual features and the other using the baseline clinical measures as predictors. Each model was trained to predict 8 week EH, defined as an endoscopy subscore of the Mayo score equal to 0 or 1. We performed 5-fold cross validation and reported the average Area Under the Receiver Operating Curve (AUROC).
This study, carried out under YODA Project # 2024-0668, used data obtained from the Yale University Open Data Access Project, which has an agreement with JANSSEN RESEARCH & DEVELOPMENT, L.L.C.. The interpretation and reporting of research using this data are solely the responsibility of the authors and does not necessarily represent the official views of the Yale University Open Data Access Project or JANSSEN RESEARCH & DEVELOPMENT, L.L.C.. The original proposal can be found: https://yoda.yale.edu/data-request/2024-0668/.

Results

For the placebo arm, our best performing model using AI visual features predicted 8 week endoscopic healing with an AUROC of 0.78, compared to 0.70 for our best performing model using the combination of 21 baseline clinical measures.
For the drug arm, our best performing model using AI visual features predicted 8 week endoscopic healing with an AUROC of 0.75, compared to 0.72 for our best performing model using the combination of 21 baseline clinical measures.
For models using baseline clinical measures, table 1 shows the importance factor for select measures across arms, calculated using XGBoost built in feature importance.

Conclusion

Our results demonstrate AI analysis of baseline colonoscopy videos with the EndoDINO AI foundation model provides robust accuracy for predicting 8 week EH in ulcerative colitis patients in both placebo and drug arms. AI placebo response prediction could be used in future trial design as covariate analysis to increase statistical power or reduce necessary sample size.
In future work, we aim to improve predictive power by combining our AI visual features with the most important baseline clinical measures through different modeling techniques.

References

Sands BE, Sandborn WJ, Panaccione R, et al. Ustekinumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2019;381(13):1201–1214. doi:10.1056/NEJMoa1900750

Disclosure

AK, PD, MC, and MS are employees of Virgo Surgical Video Solutions, Inc., which developed technology used in this work.

Introduction

The Tokyo Guideline 2018 recommends laparoscopic cholecystectomy as the gold standard therapy for acute cholecystitis regardless of the severity and the onset of symptoms, as long as the patient is fit for surgery. Approximately 20% of the patients undergo acute cholecystectomy in our region, and in the remainder of the patients, we have to take into consideration the likelihood of recurrent inflammation after the regression with conservative therapy. According to the TG 2018, the drainage of the gallbladder is recommended in grade II and grade III cholecystitis. This can be carried out by interventional radiologist as percutaneous transhepatic gallbladder drainage (PTGBD), by endoscopist as transpapillary gallbladder drainage (TPGBD) or endosonography-guided gallbladder drainage (EUS-GBD).

Aims & Methods

The primary endpoint of our prospective, non-randomized, observational study was to determine the technical (successful stent implantation into the gallbladder) and clinical success (repeated need for drainage and absence of recurrent cholecystitis) of TPGBD in those patients that underwent it from 01.01.2023 at the University of Szeged. Our secondary endpoint was the comparison of the time of hospitalization between the patients who underwent clinically successful TPGBD and those who underwent PTGBD for grade II/III cholecystitis.

Results

Altogether 19 patients had undergone TPGBD, 74% of them were female, the average age was 64,53. Previously 21% had cholecystitis, 47% had cholecystolithiasis, while 16% had choledocholithiasis and 11% of the patients gone under PTGBD. TPGBD was carried out because of grade II cholecystitis in 89% of the patients, and grade III in the rest of them. 63% was considered at least a 3 in the ASA physical status classification. Altogether the technical success rate was 58%, a cholangioscop was used in 37% of the cases. The successful canulation rate of the bile duct was 89%, while the canulation rate of the cystic duct was 68%. There were two cases, where after the canulation of the cystic duct the implantation of the plastic stent was not possible. 3 patients were referred for PTGBD after an unsuccessful TPGBD, the remainder patients with an unsuccessful TPGBD received conservative therapy. After a technically successful TPGBD, only one patient went under PTGBD due to his severe comorbidities, rather than a repeated TPGBD. 6 patients underwent cholecystectomy averagely in 8,5 weeks after the TPGBD, the remainder of patients did not have neither the need for repeated drainage nor any symptoms requiring urgent care due to cholelithiasis. Comparing this group with 11, randomly chosen patients who underwent PTGBD for at least grade II cholecystitis during the period of the study, we detected that the time of hospitalization after the drainage was less (8,2 days vs 13,3 days), and less patients required repeated drainage or had recurrent cholecystitis (1 vs 4).

Conclusion

Although TPGBD imposed a great challenge before the use of cholangioscop in everyday practice, nowadays it is becoming an accepted part of the therapeutic algorithm in the treatment of cholecystitis, where an acute cholecystectomy is not performed. Our results suggest that TPGBD can lead to shortened hospitalization and have less complications than TPGBD. Our findings will serve as a basis for a future extension of the study and for the design of a randomised prospective study with a control group.

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