Introduction

Tofacitinib (TFB) is suggested to be an effective therapeutic option for ulcerative colitis (UC) and has even been implicated in the treatment of acute UC (ASUC). However, available data on the efficacy of TFB in the above indications from real-world studies are limited by cohort size.

Aims & Methods

We aimed to investigate the effectiveness and safety of TFB in moderate to severe colitis and ASUC. A retrospective, international, multicenter cohort study, enrolling UC patients with ≥6-week follow-up period was conducted between February 1 and July 31, 2022. Indications for TFB were categorized to ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Primary outcome was steroid-free remission (SFR), defined as partial Mayo score ≤ 1, no rectal bleeding and no steroid admission. Major secondary outcome was colectomy, and safety data were also analyzed.

Results

A total of 391 UC patients (median age 38 [IQR: 28-47] years; follow-up period 26 [IQR:14-52] weeks) were included. 27.1% of the patients received TFB for ASUC. SFR, as primary outcome, was achieved in 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. Baseline pMayo (OR: 0.850; p=0.006) was negatively associated with SFR at week 12. Biologic naive patients (OR: 2.078; p=0.04) more likely achieved week 52 SFR (56.8 % vs. 38.7 %). The colectomy rate at week 52 was significantly higher in the ASUC group (17.6% vs. 5.7%; p<0.001). Risk factor of colectomy was decreased with age (OR: 0.94; p=0.013). 67 adverse events were reported, and 17.9% resulted in the cessation of TFB. Thromboembolic event was reported in one patient.

Conclusion

TFB is equally effective in ASUC and chronic activity both in short-term and long-term. Higher baseline disease activity and previous biological therapy decreased the therapeutic efficacy. No new adverse event signals was found.

Disclosure

Daniela Pugliese received speaker fees from MSD, Takeda, Galapagos and Janssen, Pfizer; advisory board fees from Pfizer.
David Drobne is a speaker, consultant and an advisory board member for MSD, Abbvie, Takeda, Pfizer, Janssen, Amgen, Biogen and Krka.
Lukas Milan has been a speaker for: Abbvie, Takeda, Celltrion, Biogen, Janssen Cilag.
Peter L. Lakatos has been a speaker and/or advisory board member: AbbVie, Amgen, BioJamp, Bristol Myers Squibb, Fresenius Kabi, Genetech, Gilead, Janssen, Merck, Mylan, Organon, Pendopharm, Pfizer, Roche, Sandoz, Takeda ,Tillots and Viatris and has received unrestricted research grant: AbbVie, Gilead, Takeda and Pfizer.
George Michalopoylos has received speaker fees from Abbvie, Takeda, Janssen, and Pfizer.
Klaudia Farkas has received speaker’s honoraria from AbbVie, Janssen, Ferring, Takeda, and Goodwill Pharma.
Tamás Molnár has received speaker’s honoraria from MSD, AbbVie, Egis, Goodwill Pharma, Takeda, Pfizer, Janssen, Sandoz, MundiPharma, Phytotec, Roche, Fresenius, and Teva.
Nitsan Maharshak has received speaking and/ or consulting fees from Pfizer, Takeda, Janssen, Ferring, BiomX, BMS, Nestle, Trobix and grant support from Takeda, Janssen, Abbott, Abbvie, Pfizer, BMS, Corundum Innovation Ltd, Nestle.

Introduction

Esophageal cancer (EC) is the eight most common cancer worldwide and causes the sixth highest number of deaths per year. The incidence of EC in Norway has increased by over 20 % over the past two decades, and a similar increase is seen in other Western countries. The overall five-year survival is approximately 20 %, which makes it one of the most fatal malignancies. Tumour stage at diagnosis is the main prognostic factor, and an early diagnosis is of most importance to improve survival. Upper endoscopy (UE) with biopsies is the standard procedure for diagnosing EC. However, several studies have questioned the efficacy of UE for diagnosis of esophageal neoplasms. The rate of missed esophageal cancers (MEC) at UE is of concern in many Western countries which have been reported to account for 6.4 to 12.7 % of all ECs. We aimed to calculate the rate of MEC and identify factors associated with MEC in Central Norway.

Aims & Methods

Retrospective population-based cohort study including 625 patients diagnosed with esophageal cancer (EC) in Central Norway 2004-2021. EC cases were identified by a search in the Cancer Registry of Norway, using ICD-10 codes C15x, and contained information about histological diagnosis and tumour localization. The dataset was verified by manual review of electronic patient records. MEC was defined as EC diagnosed 6-36 months after a previous non-diagnostic upper endoscopy. Clinical and disease variables were extracted from patient records. The rate of MEC in Central Norway was calculated annually and for the study period overall. Factors possibly associated with MEC, including tumour localization, histological type, as well as symptoms and findings were recorded. The median time interval from prior UE to date of diagnosis was calculated, as well as biopsy rates of patients with Barrett´s esophagus (BE) and ulcers at the prior UE.

Results

There were 625 patients in the entire cohort. The majority (n=404, 64.6%) were localized in the lower third of the esophagus and were adenocarcinomas (n=356, 57.0%). Fifty-one (8.2%) cancers were MEC. There was a significant increase in annual numbers of EC (p=0.001) and MEC (p=0.007) over the study period, but no increase in MEC rate (p=0.393). MEC patients were older than controls (74.0 years vs. 70.2 years, p=0.038), whereas sex did not differ significantly between MEC and controls. MEC was not associated with localization, sex or histological type. The most common findings at the prior UE were hiatus hernia (n=27, 52.9%), BE (n=26, 51.0%) and esophagitis (n=10, 19.6%), while the most common alarm symptom was gastrointestinal bleeding (n=11, 21.6%). The median time from prior UE to MEC diagnosis was 23.0 (6.2-35.6) months. In all patients with histological dysplasia (n=10) at the prior UE the follow-up interval was longer than recommended in current guidelines. A total of 24% of patients with either BE or an ulceration were not biopsied at UE preceding the MEC diagnosis.

Conclusion

MEC accounted for 8.2% of esophageal cancer in Central Norway. MEC was associated with higher age at diagnosis. There was no association between MEC and histological type or localization and a thorough examination of the entire esophagus is necessary to reduce MEC rates. Inappropriate follow-up of endoscopic BE, histological dysplasia or ulcerations were identified as preventable causes. Awareness of MEC, and more consistent biopsies of ulcerations and BE could reduce the MEC rate.

Disclosure

No conflict of interest.

Introduction

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease with unknown causes. Patients experience periods with active disease and symptoms such as diarrhoea, pain and weight loss. Little is known about environmental factors that trigger flare-ups, including the effects of commonly used medications. Recent studies suggest a link between microbial factors and IBD, making it important to investigate the impact of antibiotics on flare-ups.

Aims & Methods

We aimed to investigate whether certain antibiotics increase the risk of flares in patients with IBD. We utilized a previously described¹ cohort of all patients with IBD in Denmark between 1974 and 2018. The cohort is based on the Danish Nationwide Patient Registry, which registers all healthcare related visits, treatments and procedure on an individual level. We utilized data between 1994 and 2018 and two distinct cohorts was created for the purpose of identifying flares. The first cohort was characterized by having an IBD-related hospital stay. The second cohort was characterized by experiencing a flare of IBD in need of systemic steroids. Patient were matched 1:5 using K-nearest neighbour. Antibiotics were grouped into the 3rd level of the Anatomical Therapeutic Chemical (ATC) classification system, with anthelmintics grouped into the 2nd level due to low numbers and all given within 60 days before the outcome. Logistic regression analysis was used to calculate odds ratios (ORs) with a 95% confidence interval (95% CI), with adjusting variables including year of remission/flare, sex, age at diagnosis, year of diagnosis, type of IBD, socioeconomic status², use of 5-ASA, use of budesonide, use of immunosuppressants, and use of subtypes of biologics.

Results

There were in total 69,908 IBD patients in the original cohort. After applying the abovementioned algorithm, a total of 15,636 and 5,178 patients were included in the cohort for hospitalisation and steroid use, respectively.
Using a multivariate logistic regression model, both cohorts observed a significant increase in odds ratios for certain antibiotics in relation to hospitalization and steroid course. Specifically, for the need of a course of steroids, quinolones (OR 3.83 (95% CI: 2.73-5.35)), antimycotics (OR 2.30 (95% CI: 1.53-3.40)), agents against amoebiasis and protozoal (OR 2.06 (95% CI: 1.39-3.01)), betalactam antibiotics (OR 1.35 (95% CI: 1.10-1.66)), and intestinal anti-infectives (OR 2.12 (95% CI: 1.08-3.98)) were associated with an increased risk for a flare requiring steroids.
Regarding the need for an IBD-related hospitalization, agents against amoebiasis and protozoal (OR 3.48 (95% CI: 2.72-4.44)), quinolones (OR 3.10 (95% CI: 2.48-3.86)), intestinal anti-infectives (OR 2.42 (95% CI: 1.54-3.76)) and antimycotics (OR 1.58 (95% CI: 1.17-2.12)) were all found to be significantly associated.

Conclusion

This study provides evidence that certain types of antibiotics increase the risk of flare-ups in patients with IBD. Quinolones, antimycotics, agents against amoebiasis and protozoal, betalactam, and intestinal anti-infectives were all associated with increased odds ratios for hospitalization and a need for a course of steroids. These findings highlight the importance of carefully considering the use of antibiotics in IBD patients and the need for further research on the effects of different antibiotics on disease progression.

References

¹ Lo B, Zhao M, Burisch J. Identifying patients with inflammatory bowel disease in the Danish National Patient Register. Dan Med J. 2023 Mar 27;70(4):A07220458. PMID: 36999818.
² https://www.dst.dk/en/Statistik/dokumentation/nomenklaturer/socio

Disclosure

An unrestricted grant was received from the Aage og Johanne Louis-Hansens Fond to support this study.

Introduction

The treatment of symptomatic hemorrhoidal disease (HD) in patients with bleeding disorders (BD) is challenging. This vulnerable group benefits the most from less invasive office-based procedures associated with low bleeding complications, namely polidocanol foam sclerotherapy (PFS).

Aims & Methods

The present study aimed to compare the efficacy and safety of polidocanol foam sclerotherapy (PFS) in the treatment of hemorrhoidal disease (HD) in patients with and without bleeding disorders (BD).
This was a prospective, multicentric, cohort study that enrolled patients with symptomatic internal HD grades I-III with BD (group B) and without BD (group A) following a 18-months period. HD baseline severity was assessed using the Goligher classification, the hemorrhoidal disease bleeding grade (HDBG) and the Sodergren hemorrhoid symptom severity (SHSS) scoring system. Both groups were treated with PFS prepared according to the Tessari´s technique. Patients with congenital BD did not perform prior bleeding prophylaxis and patients with acquired BD due to antithrombotic drugs did not discontinue therapy. The efficacy outcomes included therapeutic success (defined by an improvement of HDBG and SHSS score over baseline) and recurrence of HD (defined by HDBG and SHSS score greater than at the end of the intervention period) during a 12-months follow-up period. The safety outcomes comprised the rate and severity of complications related to PFS.

Results

The study included 228 patients (Group A: 155; Group B: 73). At baseline, the group B presented higher HDBG (p<0.001) and SHSS (p=0.019). The overall therapeutic success rate was 93.4% with an average number of sessions of 1.51±0.74, significantly higher for group B (1.68±0.86 vs 1.43±0.65, p=0.013). A 11.4% complications rate was reported, the majority were mild (96.2%); bleeding complications occurred in 4.8% of the patients. No significant differences were reported between the two groups concerning therapeutic success, recurrence rate, and complications rate.

Conclusion

Patients with BD may present with more symptomatic HD at baseline. Nevertheless, PFS decreased hemorrhoidal bleeding and symptom severity with low incidence of complications in these patients, demonstrating similar effectiveness and safety comparing to patients without BD. Notably, performing PFS did not expose patients with BD to an increased thrombotic risk.

Introduction

Radiofrequency ablation is considered the standard therapy for flat dysplastic BE. Hybrid APC is a newer under evaluation, less expensive technique, but with the need of a special injection device and catheter. Aim of the study: To evaluate the efficacy of a standard APC catheter after submucosal injection for BE ablation.

Aims & Methods

To evaluate the efficacy of a standard APC catheter after submucosal injection for BE ablation. Naïve or after previous treatments patients with BE and low - grade dysplasia (LGD) were prospectively evaluated. Sodium chloride solution 0.9% was injected submucosally with a 23 G needle followed by APC application with a standard catheter (ERBE APC 300, 45Watts) on the created cushion. The same procedure was repeated for most of BE surface to be cauterized, with special attention not to ablate large circumferential areas. Patients were under high dose PPIs. Biopsies were taken according to the Seattle protocol during the follow-up.

Results

31 patients, 28 males (90.3%), 56.7±12.5 years old. Their initial diagnosis was: 19 patients with LGD (61.3%), 7 with high grade dysplasia (22.6%), and 5 with intramucosal cancer (16.1%). Eleven patients (35.5%) had previous endoscopic mucosal resection (EMR) while 7 (22.6%) had received radiofrequency ablation (RFA). Median BE length with LGD at the beginning of APC was 4cm (25th-75th:2-7, min-max:1-10). Median follow-up:10.1(1-108) months. In total 20 (64.5%) patients completely eradicated BE. For the remaining 11 patients APC led to a substantial reduction of BE length [Initial Median: C3M6 (Min: C0M1, Max: C6M8) to a final median: C0M2 (Min:C0M1, Max:C2M5] but the study is ongoing. Initial BE length was correlated to APC sessions needed (r= 0.54, p<0.01) but was not a limiting factor for complete BE eradication. Instead, smoking was an aggravating factor for BE complete eradication (HR=3.12, 95%CI.: 1.2-8.12, p=0.02). No death, hospitalization, severe hemorrhage, or perforation were observed. In 7 patients moderate pain requiring paracetamol, resolved after a few hours of in hospital supervision while 11 patients had mild dysphagia the following days without permanent stenosis.

Conclusion

Conclusions: 1) Standard APC after submucosal injection is safe and tolerable for BE ablation. 2) It may be applied in naïve patients or if other techniques were previously used. 3) Length increases the number of sessions needed but does not seem to be a limiting factor for APC application.

Introduction

The current gold standard for diagnosis of Inflammatory bowel disease (IBD) is based on clinical and endoscopic evaluation as well as histologic and radiologic evaluation. However, endoscopic evaluation can be uncomfortable and carry some risks, especially in the pediatric population that requires general anesthesia in order to perform the procedure.

Aims & Methods

Our aim was to investigate whether serum biomarkers can differentiate between pediatric patients with and without IBD. Secondary aims were to determine whether there are biomarkers that can differentiate between Crohn's disease (CD) and Ulcerative colitis (UC), and whether we can predict progression to biologic treatment within one year from diagnosis using these biomarkers.
Pediatric patients undergoing a first diagnostic colonoscopy at British Columbia Children's Hospital (BCCH) between December 2019 and June 2022 were invited to participate in the study. A 2 ml blood sample was taken from each participant at the time of colonoscopy. Demographic and clinical data were collected from each patient. Blood samples were analyzed using the Legendplex^TM flow cytometry kits investigating which included 50 different inflammatory cytokines and chemokines associated with IBD. A prediction model was built via a supervised learning method to determine how well we can predict the different groups.

Results

One hundred pediatric patients participated in the initial study. Five were excluded from the analysis due to uncertain diagnosis. Median age was 13.36 years, 39 were females (41%) and 54 (56.84%) were diagnosed with IBD, with 35 (64.81%) diagnosed with Crohn's disease. On a univariate analysis and Volcano plot 6 biomarkers were found to be strongly associated with the diagnosis of IBD: IL22, IL8, TARC, GROA, MIG, and IL18. The cross-validated AUROC was 0.70. Using SPLS-DA the classification accuracy was improved to 0.84, and MIG was found to be the key biomarker to discriminate between pediatric IBD patients and non-IBD patients.
On a univariate analysis only TSLP was found statistically significant as a predictor of CD, and RANTES and TARC were found as negative predictors for initiating biologic treatment within one year of diagnosis. However, the prediction model did not predict well the subclasses nor progression to biologic treatment.

Conclusion

Using serum biomarkers can predict the diagnosis of Pediatric IBD. MIG was found to be the key biomarker in the prediction model.