Introduction

Patients with acute severe ulcerative colitis (ASUC) are at increased risk of colectomy following an episode of acute severe exacerbation. Medical rescue therapy in steroid non-responders has reduced the need for emergency colectomy. However, the impact of biologics on longer-term colectomy risk is unclear.

Aims & Methods

A retrospective cohort study of adult patients aged ≥18 years hospitalized with acute exacerbation of UC requiring hospitalization and managed with intravenous corticosteroids between 2010 and 2022 at two regional hospitals in London, Ontario, Canada. Steroid non-response was defined as requirement of medical rescue therapy or colectomy.

Results

A total of 264 adults hospitalized with ASUC were included in the analysis (male: 51.1%[n=136], mean age at admission: 40.8±17.8 years). The majority had extensive colitis (71.3% [n=169]) at the time of diagnosis. 46.3% (n=118/255) presented within one year of disease onset and 23% (n=61) had ASUC as their first presentation with UC. 25.7%(n=66/257) of patients had prior purine analogues and 23.3% (60/257) had previous biologics prior to ASUC presentation. After admission, 55.7% (n=147) responded to intravenous corticosteroids. Of the steroid non-responders, 37.5% (n=99) patients were managed with infliximab rescue therapy and only one patient received tofacitinib rescue therapy. Median CRP, stool frequency and Lindgren index score were statistically significant between steroid responders and non-responders (Table 1). A higher proportion of steroid non-responders had prior exposure to biologics or tofacitinib compared to steroid responders (31.9%vs16.3%, p<0.01). On multivariate analysis for various factors predicting steroid non-response, assessment by Oxford criteria on day 3 was the only factor that was statistically significant (odds ratio 4.70 (95% CI[1.06-20.8]), p=0.04). Oxford criteria on day 3 had a sensitivity, specificity of 58.6% and70.8%, respectively for predicting steroid non-response. 8% (n=21) required colectomy during index admission. An additional 13% (n=32) underwent colectomy within 12 months of discharge, for which there was no difference between steroid responders and non-responders (12.2% vs 14.7%). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 8% (20/245) and 5.4% (12/223) respectively. Hospitalization with UC exacerbation following discharge was 17% (38/223).

Conclusion

8% of patients admitted for ASUC require colectomy during the same admission and additional 13% required colectomy within 12 months of discharge. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates remain high.

Table 1: Baseline characteristics and outcomes in adult patients with ASUC with comparison between steroid responders and non-responders

Disclosure

SKV: None
LA: None
TADS: None
MA: None
VS: None
LG: None
EC: has received an educational grant and speaker fees from AbbVie, Pfizer, and consulting fees from Alimentiv Inc., Sanofi.
TP: has received Advisory Board/consultant fees from Bristol Myers Squibb, Celltrion, Eli Lilly, Organon and Pfizer recently. He currently serves as an investigator on clinical research studies for Abivax, Alimentiv, Applied Molecular Transport, BristolMyersSquibb, Eli Lilly, Prometheus/Merck and Takeda.
MB: Honoraria: Shire, Allergan, Pfizer, Takeda, Advisory Boards, AbbVie, Takeda, Janssen, Lupin, Gilead, Pfizer, Novo Nordisk, McKesson, Innomar, Clinical Trials: AbbVie, Novo Nordisk, Gilead, Takeda, Boehringer Ingelheim, Janssen, Pfizer, Astra Zeneca, Intercept, Research Publications: Abbvie (2021 – Letter signed)
JG: received speakers fees from AbbVie, Janssen, Takeda, Celltrion, Organon and Ferring
BY: None
MS: None
VJ: has received has received consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, SCOPE, Second Genome, Sorriso, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi

Introduction

Ustekinumab (UST) is a monoclonal antibody against the p40 subunit, common to IL-12 and IL-23 and was approved recently for the treatment of moderate to severe ulcerative colitis (UC).

Aims & Methods

The aim of this ongoing study is to report and analyze data from a large cohort of Greek patients with UC, who receive treatment with UST. We collected data from patients with UC from 14 Greek hospitals who commenced treatment with UST and evaluated their clinical response at week 16. Clinical response was defined as 50% reduction in the UC PRO2 values at week 16 compared to the values before treatment (baseline).

Results

Herein, we report the clinical outcomes at week 16, following the completion of induction regimen (i.v. loading 6mg/kg plus 1^st 90mg sc injection at week 8). The demographics and disease characteristics of the first 101 enrolled patients are shown in Table 1. The majority of patients (70, 70%) commenced treatment with UST due to active disease despite previous treatments. Seventy-six patients (76%) had been exposed to at least one biologic agent, most commonly anti-TNFs (54%). Thirty-eight (38%) and 29 (29%) patients were exposed to one and two biologics, respectively. Sixteen patients (16%) had previously received both infliximab (IFX) and vedolizumab (VDZ). Corticosteroids (50%) and mesalazine (5-ASA, 68%) were the most common concomitant treatments. UST was discontinued in 4 patients due to no response. A total of 79 patients have reached the 16^th week time-point, out of whom 61 have enough data to be analyzed. Analysis of the patients who had active disease at induction (total number with adequate data: 50) showed that clinical response was achieved in 36 (72%) and clinical steroid-free remission in 23 (46%) patients. In multiple logistic analysis concomitant use of 5-ASA was associated with a higher probability of clinical response at week 16 (P=0.009), while hemoglobin >13.1g/dL (P=0.047), and age >60 years (P=0.059) were associated with a lower probability of response. Seven patients were receiving concomitant corticosteroids at week 16.

Conclusion

In a real world clinical setting, UST was mostly used as a 2^nd or 3^rd line treatment for moderate to severe UC. At the end of induction treatment, the majority of patients showed clinical response and almost half were in steroid-free remission. Positive predictive factors of response to UST included the concomitant use of 5-ASA, while Hb >13.1 g/dl and age >60 years were associated with lack of response.
Funding: This study was funded through a research grant from the Greek IBD study group (EOMIFNE) to G.B. EOMIFNE grant: 2022EOMIFNEmp1

Disclosure

GB: Advisor/lecturer for Janssen, Pfizer, Takeda, Abbvie, MSD, Mylan, Genesis Pharma,
Adacyte Therapeutics, Amgen, Ferring, Cooper; Funding (Grants/Honoraria): Pfizer, Takeda,
Abbvie, Aenorasis; Research/Clinical Trials: Abbvie, Takeda.
EZ: Advisor/lecturer for Pfizer, Takeda, Abbvie, Amgen, Genesis Pharma, Aenorasis, Janssen
SM: Advisory/Lecturer for Pfizer, Takeda, Abbvie, Ferring, MSD, Janssen
GM: Advisor/lecturer for AbbVie, Celgene, Celtrion, Ferrirng, Genesis, Hospira, Janssen,
Millennium Pharmaceuticals, MSD, Mylan, Pharmacosmos, Pfizer, Takeda, VIANEX, Angelini,
Falk Pharma, Galenica, Omega Pharma; Consultancies for MSD and Takeda; Research support
from AbbVie, Galenica, Genesis, Menarini Group, MSD, Pharmathen.
KK: Advisor/lecturer for Abbvie, Aenorasis, Janssen, MSD, Pfizer and Takeda, Amgen, Ferring,
Galenica, Genesis Pharma.
MT: Advisor/lecturer for Janssen, Pfizer, Takeda, Abbvie, MSD, Mylan, Genesis Pharma,
Amgen, Research/Clinical Trials: AbbVie, Gilead, Takeda

Introduction

First-line approach for complicated acute diverticulitis is conservative treatment with bowel rest and systemic antibiotics. The presence of pericolic, mesocolic, or distant (usually deep pelvic) abscess ≥4 cm (1a or II stages according to Hinchey classification) represents an indication for drainage, either trans-abdominal, trans-gluteal, trans-rectal, or trans-vaginal. Endoscopic-ultrasound-guided pelvic abscess drainage (EUS-PAD) with lumen-apposing metal stents (LAMS) has been reported as a safe and effective alternative approach for complicated diverticular disease.

Aims & Methods

We aimed to assess the safety and efficacy of EUS-PAD with LAMS in a homogeneous population of patients with acute diverticulitis complicated by a pericolic, mesocolic, or pelvic abscess. A multicenter study was conducted from 2019-2023 retrieving all consecutive patients who underwent EUS drainage attempts for complicated acute diverticulitis in three referral centers. All cases have been considered suitable for EUS-PAD by local multidisciplinary teams. Continuous variables are expressed as median [interquartile range].

Results

Sixty-six patients underwent EUS assessment with interventional intent; however, in 13 cases, no sign (no. 5) or a small abscess (no. 8) was found. Finally, 53 patients (29 female 54.7%) with a median age of 74 [62-83] year-old were considered. Most cases (no. 40, 75.5%) had a pelvic abscess (Hinchey stage II) while 13 (24.5%) had a para-colonic abscess (stage 1b); thirty-one (58.5%) did not receive any antiplatelet or anticoagulant agent, while 10 (18.9%) were on low molecular weight heparin, and 12 (22.6%) on antiplatelet agents. No patient had fecal diversion. The median abscess size was 50 [40-60] mm. EUS-PAD have been conducted under conscious sedation in 14 (26.4%), deep sedation in 12 cases (22.6%), or general anesthesia in 27 cases (50.9%) with electrocautery-enhanced LAMS (Hot Axios, Boston Scientific, US). Six patients (11.3%) underwent concomitant percutaneous drainage, while in one case (1.9%) two LAMS have been used. In 34 cases (64.2%) trans-rectal EUS-PAD was performed, in 19 (35.8%) a trans-colonic route was required. Technical success was achieved in 49 (92.5%). A trend toward a higher technical success rate was observed for the trans-rectal route (odd ratio 6.19; 95% C.I 0.60 - 64.3; P 0.13); abscess size ≥50 mm was independently related to a higher technical success rate (OR 18.0 [1.63 - 198]; P 0.02). Stent size was 6x8mm (no. 2), 8x8 mm (no. 11), 10x10mm (no. 20), 15x10mm (no. 15), and 15x15mm (no. 1). Clinical success rate was 88.7%. The incidence of adverse events was 3.8%, with 1 minor procedural bleeding (AGREE II) and one late proximal migration (AGREE IIIa). LAMS were removed after a median of 19 [14-28] days and substituted with a double pigtail plastic stent in 9 cases. Patients were followed for 12 [8-12] months. Four (7.5%) patients underwent urgent Hartmann sigmoidectomy; during follow-up 12 (22.6%) patients required elective surgery; finally, 2 (3.8%) patients presented recurrent diverticular abscesses. No procedure-related or disease-specific mortality was observed during follow-up.

Conclusion

EUS-guided pelvic abscess drainage (EUS-PAD) with LAMS could be considered a safe and effective approach among conservative treatments for complicated acute diverticulitis.
EUS drainage with LAMS was confirmed as an effective treatment modality for encapsulated collections larger than 5 cm and close to colonic wall; trans-rectal approach seems safer while no difference in stent size were observed in terms of safety and efficacy.

References

Fugazzola P, Ceresoli M, Coccolini F, et al. The WSES/SICG/ACOI/SICUT/AcEMC/SIFIPAC guidelines for diagnosis and treatment of acute left colonic diverticulitis in the elderly. World J Emerg Surg. 2022;17: 5.
Nagata N, Ishii N, Manabe N, et al. Guidelines for Colonic Diverticular Bleeding and Colonic Diverticulitis: Japan Gastroenterological Association. Digestion. 2019; 99 (Suppl 1): 1-26.
Kruis W, Germer CT, Böhm S, et al. German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) and the German Society of General and Visceral Surgery (DGAV). German guideline diverticular disease/diverticulitis: Part II: Conservative, interventional and surgical management. United European Gastroenterol J. 2022; 10: 940-957.
Donatelli G, Cereatti F, Fazi M, et al. Endoscopic ultrasound-guided drainage of intra-abdominal diverticular abscess. A case series. J Minim Access Surg. 2021; 17: 513-518.
Poincloux L, Caillol F, Allimant C, et al. Long-term outcome of endoscopic ultrasound-guided pelvic abscess drainage: a two-center series. Endoscopy. 2017; 49: 484-490.
Lisotti A, Cominardi A, Bacchilega I, et al. EUS-guided transrectal drainage of pelvic fluid collections using electrocautery-enhanced lumen-apposing metal stents: a case series. VideoGIE. 2020; 5: 380-385.

Disclosure

Andrea Lisotti had a proctorship contract with Boston Scientific in 2021 and 2022.

Introduction

The underwater immersion technique has so far been used for the resection of sessile polyps, with satisfactory results in terms of efficacy and complications (due to the use of water instead of medical air (CO2) and the absence of fluid substances in the submucosa.

Aims & Methods

The aim of this work is to demonstrate the effectiveness of the underwater technique for diagnostic purposes, in patients suffering from diverticular disease with insurmountable stenosis at traditional colonoscopy.A cohort of 50 patients (20 D and 30 U - mean age 72 years) with incomplete colonoscopy due to stenosing diverticular disease ( DICA 4) confirmed by CT colon ( virtual colonoscopy) examination was enrolled. Previously, all the patients had been evaluated at other endoscopy centers , and studied at the Gastroenterology and Digestive Endoscopy Center of the Benevento ASL, subsequently for the detection, in at least 15 patients, of lesions compatible with polyps > 6 mm on the colon CT scan. All patients underwent colonoscopy under conscious sedation with a thin colonoscope (Olympus PTH PF 190), filling the stenotic lumen with water instead.

Results

In 41 patients, the use of the UW technique allowed the stenotic section to be overcome, allowing the examination to be completed; in the remaining 9 the stenosis was insurmountable. In the 15 patients with lesions compatible with polyps > 6 mm on colon CT, only 5 pts were positive, 2 of which with the finding of polypoid formations > 1 cm in sections other than those reported on colon CT. No complications were recorded both in the diagnostic phase and in the operative phase.

Conclusion

The UNDERWATER technique can represent an alternative method in the diagnosis of certain pathological and inflammatory conditions with a high risk of perforation. The irrigation of the colonic lumen with water also allows the magnification of the mucosa, improving the identification and treatment of polypoid lesions (particularly the sessile ones).

References

A.Tursi et al Dica endoscopic class. for diverticular disease shows a significant interobserver agreement among community endoscopist . J Gastroint Liver Dos 2019 : 28 (1) 23-27.
A.Tursi et Al Prognostic value of Dica score J . Clin. Gastroenterology 2016
Y.Takeuchi et al Underwater endoscopic mucosal resection for colonrectal polyps lesions: can it be an underwater revolution?DEN Open 2022, 2 e84