Introduction

Swallowed Topical Steroids (STCs) originally developed for airway administration have been used off-label for eosinophilic esophagitis (EoE). Recently a new specifically designed formulation of budesonide orodispersible tablet formulation (BOT) has been developed and approved in different European countries. Since 30/08/2022 in our center all patients treated with STCs have been switch to BOT and prospectively followed up clinically and histologically.

Aims & Methods

The aim of our study is to evaluate efficacy, safety and patient’ satisfaction of therapeutic switch from off-label STCs to BOT (NCT05594849). Each patient performed upper GI endoscopy with biopsies under STCs and after 12-16 weeks of BOT to evaluate histologic remission. Moreover, all patients filled up a set of questionnaires before the switch and after 12-16 weeks of BOT evaluating severity of symptoms (DSS, DSQ), quality of life (EoE QoL) and satisfaction of the treatment (19 items scored between 0 to 4 evaluating the modality of assumption, the taste, and the perception of safety; higher values corresponding to higher satisfaction).

Results

The sample consists of 29 EoE patients, PPI non responders, who were receiving STCs (72.41% home-made viscous fluticasone, 27.58% viscous budesonide). Mean treatment-time was 32.53±29.27 months for fluticasone and 23.5±11.01 months for budesonide. Six patients (20.68%) presented strictures previously treated endoscopically. The starting dose of BOT was determined on the previous dosage of STCs and on the presence of histologic remission (89.65% used 1 mg twice daily, 10.34% 1 mg daily). Of 29 enrolled patients, 19 have already repeated the endoscopy under BOT (65.51%). Before therapeutic switch, 8 patients over 19 (42,11%) were active (>15 EOS/HPF) and 11 patients (57.89%) were in histologic deep remission (<6 EOS/HPF). After therapeutic switch, 7 patients over 8 (87.5%), histologically active under STCs, achieved deep remission with BOT, and one remained active (12.5%). Between patients in deep remission with STCs, 10 patients over 11 mantained histologic deep remission (90,91%) and only one relapsed (9,09%) after switch. After the switch to BOT, 3 patients over 29 presented oral/esophageal candida infection. Of these three, two patients have already experienced oral/esophageal candida under off-label STCs. After the therapeutic switch an improvement of symptoms severity was found for DSS score but not for DSQ (STCs-DSQ 0.24±0.63, BOT-DSQ 0.16±0.57, p value=0.60; STCs-DSS 5.14±2.77, BOT-DSS 2.3±2.05, p value=0.012). No differences were found for the quality of life (STCs-EoE QoL 42.07±19.42, BOT EoE QoL 30.72±23.95, p value=0.068). Finally, the satisfaction score showed a significant major willing of assumption of BOT rather than STCs (STCs 38.21±11.61, BOT 55.91±14.30, p value= 0.003).

Conclusion

Preliminary data of our study showed that therapeutic switch from off-label STCs to BOT in EoE patients is effective, safe and well tolerated. Most of patients histologically active under off-label STCs achieved histological deep remission with BOT and, if previously acquired with off-label STCs, histological deep remission was maintained in the majority of patients under BOT. The patients reported a significant major willing of assumption of BOT rather than off-label STCs.

Introduction

As a chronic condition, eosinophilic oesophagitis (EoE) requires lifelong therapeutic management and multidisciplinary care. Reports suggest clinicians managing EoE have gaps in knowledge and competence, which may lead to suboptimal patient outcomes. We aimed to assess whether a purpose-specific curriculum comprising a series of continuing medical education (CME) activities addressed these gaps.

Aims & Methods

Four faculty-led, CME-accredited activities on EoE were hosted on two free-to-access online medical education websites. Each activity provided 30–60 minutes of education in short videos and addressed learning objectives based on a review of published literature and expert insights. Educational outcomes were assessed using Moore’s expanded outcomes framework Levels 1–4 (participation, satisfaction, knowledge, and competence, respectively). Intent to change practice and need for further education were also assessed. Level 1 data were captured using Google Analytics; Level 2–4 data were captured using pre- and post-activity questionnaires administered by an independent third party and analysed by the authors. Across the curriculum 21,032 participants engaged with the content, with a sample size of 800 available for the Level 2–4 analysis; the margin of error was calculated as ~3% based on a standard confidence interval of 95%.

Results

Within 12 weeks of launch, a mean of 5,258 participants engaged with each curriculum activity (Moore’s Level 1). Mean satisfaction (Moore’s Level 2) was high (87.3%) across the curriculum. From baseline to follow-up, significant average increases in declarative knowledge (24%, p=0.012), procedural knowledge (18%, p<0.001), and competence (16%, p=0.004) were observed (Moore’s Levels 3a, 3b, and 4, respectively) (Table). Gastroenterologists had the highest proportion of correct answers at follow-up across all activities (86–95%). Allergists/immunologists had the largest increase in knowledge from baseline to follow-up (51%, activity 1); the smallest increase was seen for gastroenterologists (7%, activity 2). For all specialities, the lowest proportion of correct answers at follow-up was for questions on pathophysiology/causes of EoE (Table). Overall, 64% of learners would change their practice following participation in ≥1 curriculum activity and ~20% indicated further education would be beneficial.

Conclusion

This expert-led, CME curriculum led to significant improvements in clinician knowledge and competence surrounding the latest research and best practices in the pathophysiology, diagnosis, and management of EoE, which may lead to improvements in patient care and outcomes. Findings support further development of online, multiformat educational activities to address clinical knowledge and competence gaps. Future programs should focus on the underlying pathophysiology of EoE and how this may inform practice.

References

None

Disclosure

Stuart Carr discloses: Consulting fees/advisory board: Sanofi. Honoraria (speakers bureau): Sanofi, Biologix.
Evan S. Dellon discloses: Research funding: Adare/Ellodi, Allakos, Arena, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Shire/Takeda. Consultant: Abbott, Abbvie, Adare/ Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio. Educational grant: Allakos, Holoclara, Invea
Nirmala Gonsalves discloses: Consultant: Allakos, Astra-Zeneca, Regeneron-Sanofi, BMS, Knopp. Speaking: Regeneron-Sanofi. Royalties: Up To Date.
Salvatore Oliva discloses: Consulting fees from Sanofi.
Jonathan M. Spergel discloses: Consultant: Regeneron and Sanofi-Genzyme, Novartis, Allakos. Grants/Research Support: NIH, FARE, Regeneron, Novartis, Sanofi, Celgene. Speaker’s Bureau: Medscape.
Mário C. Vieira: No conflicts of interest associated with the submitted work to declare.
Katie Bickford, Kathy Day, Alex Noble, Anne Nunn and Alison Scott: No financial relationships to disclose.

Introduction

A low incidence of eosinophilic esophagitis (EoE) in children in the North Denmark Region (NDR) were measured in 2007-2017. Few of the children diagnosed before 2017 were treated to remission suggesting a lack of awareness. While there currently are no guidelines for treating EoE in Denmark, a new English guideline was published in 2022 renewing focus on the disease.

Aims & Methods

The aim of this study was to measure the difference of current Danish clinical practice for treatment and follow-up of EoE children in the NDR with the new English guideline from the British Society of Gastroenterology (BSG) and the British Society of Pediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN). This retrospective, register-based DanEoE cohort study included 31 children diagnosed with EoE between 2007–2021 in NDR. Medical records were reviewed and information about treatment and follow-up were collected.

Results

In 32% of the children with EoE in the NDR, first-line treatment initiated corresponded with the recommendations in the new English guideline. One in 6 children were never started on any treatment even though treatment always is recommended. Symptomatic follow-up was completed in 77% (24/31) of children and 85% (11/13) of the children after 2017. Histologic follow-up within 12 weeks was completed in 13% (4/31) of the children and 15% (2/13) of the children after 2017. Combined symptomatic and histologic remission after first-line treatment was achieved in 6% (2/31).

Conclusion

In Denmark focus on improving EoE treatment and follow-up for children is needed, as there is a significant difference between current clinical practice and the recommendations in the new English guideline.

References

Hollænder M, Terkelsen JH, Kramme F, Bredal K, Kragholm K, Dalby K, et al. The incidence of eosinophilic oesophagitis in 2007-2017 among children in North Denmark Region is lower than expected. BMC Pediatr. 2022 Apr;22(1):183.
Dhar A, Haboubi HN, Attwood SE, Auth MKH, Dunn JM, Sweis R, et al. British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults. Gut. 2022 Aug;71(8):1459–87.

Introduction

To prevent colorectal cancer, it is crucial to accurately identify and classify precancerous colonic lesions. Previous studies have shown that the classification of precancerous lesions still depends on the individual examiner. In this study, we attempted to create realistic AI-generated images for training physicians in the assessment of colorectal lesions. Artificially generated realistic images make it independent of patient data, allowing to specifically create various precancerous lesions and practice their classification.

Aims & Methods

We trained an AI using 25 million endoscopic images, that can generate images of different precancerous colorectal lesions. To show that the AI is capable of producing realistic-looking images, we designed a study in which we presented artificial polyps and real images of polyps to eleven physicians and asked them to discriminate between them. They were also asked about their level of confidence for the assignment. We used 20 real and 20 AI generated images. We included five experts and six beginners in this study. Beginners were defined as endoscopists who have performed less than 100 examinations or have been practicing for less than 2 years.

Results

Real images were identified as such with an accuracy of 79%, while only 66% of AI-generated images were recognized as artificially generated. The p-value is 0.0034. The physicians had a higher confidence when choosing an answer for real images (63%) and a lower for fake images (56%). Especially the AI-generated images that clearly showed mucosal vessels were classified as real images by many physicians.

Conclusion

In this study we were able to generate synthetic images with a high degree of authenticity. We have identified features that make images appear particularly realistic and we will continue to train the AI with these specific characteristics to achieve even higher quality. The images that were identified as most realistic will be used in further projects to classify precancerous lesions.

Introduction

Since patients with pharyngeal squamous cell carcinoma (SCC) often have multiple pharyngeal lesions, evaluation of pharyngeal lesions before endoscopic resection (ER) is important. However, detailed endoscopic observation of the entire pharyngeal mucosa under conscious sedation is difficult.

Aims & Methods

We examined the usefulness of endoscopic surveillance with narrow band imaging (NBI) and lugol staining for detection of pharyngeal sublesions during ER for superficial pharyngeal SCC under general anesthesia (endoscopic surveillance during treatment; ESDT). From January 2021 through June 2022, we examined 78 patients who were diagnosed with superficial pharyngeal SCC and underwent ER. They underwent the ESDT and for patients who were diagnosed with new lesions of pharyngeal SCC or high-grade dysplasia (HGD) that were not detected in the endoscopic examination before treatment, ER were performed simultaneously for new lesions and the main lesions. The primary endpoint of this study was the detection rate of new lesions of pharyngeal SCC or HGD in the ESDT.

Results

Fifteen of the 78 patients were diagnosed as having undetected new pharyngeal lesions in the ESDT and 10 (12.8%) (95% CI: 6.9 – 22.2%) were histopathologically confirmed to have new lesions of pharyngeal SCC or HGD. Among the 13 lesions of SCC or HGD, 8 were found by NBI observation; however, 5 were undetectable using NBI but detectable by lugol staining. All of the 13 lesions had endoscopic findings of pink color sign on lugol staining.

Conclusion

Endoscopic surveillance for pharyngeal sublesions with lugol staining during ER for superficial pharyngeal SCC is feasible and useful.

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

Filgotinib (FIL) is a once-daily, oral, Janus kinase 1 preferential inhibitor approved for the treatment of patients with ulcerative colitis (UC) in the UK, EU and Japan. In the phase 2b/3 SELECTION trial (NCT02914522),¹ FIL 200 mg (FIL200) was well tolerated and effective in inducing and maintaining clinical remission vs placebo (PBO) in patients with UC.

Aims & Methods

This post hoc analysis of SELECTION data further evaluated the prolonged benefit of FIL treatment from week 10 (W10) until W58. In SELECTION, adults with moderately to severely active UC were randomized 2:2:1 to receive FIL200, FIL 100 mg (FIL100) or PBO once daily for 11 weeks in Induction (IND) Studies A and B (biologic-naïve and -experienced patients, respectively). Patients in clinical remission or with a Mayo Clinic Score (MCS) response at W10 (responders) were rerandomized 2:1 to continue their IND FIL dose in the 47-week Maintenance (MNT) Study. This post hoc analysis evaluated the hazard ratio (HR) for protocol-specified disease worsening (PSDW) in patients who continued FIL200 during MNT (FIL200→FIL200) vs those rerandomized from FIL200 to PBO (FIL200→PBO). The proportion of patients with a prolonged benefit at W58 was also evaluated across all FIL200 and FIL100 MNT arms. A prolonged benefit was defined as clinical remission or an MCS response at W58, among W10 responders. Among patients with prolonged benefit at W58, the proportion of those who had Inflammatory Bowel Disease Questionnaire (IBDQ)-remission at W58 was also assessed across all FIL200 and FIL100 MNT arms.

Results

Baseline characteristics were similar between MNT arms, although biologic-experienced status was more common in patients who did not have a prolonged benefit vs those who did. FIL200→FIL200 treatment (n=199) reduced the risk of PSDW by 74% vs FIL200→PBO (n=98) (HR [95% CI]: 0.26 [0.17–0.40]; p<0.0001). PSDW was the most common reason for discontinuation among patients without prolonged benefit, across all arms. In the FIL200→FIL200 arm, 66.8% of patients who were in clinical remission or had an MCS response at W10 had a prolonged benefit at W58 vs 32.7% in the FIL200→PBO arm. Among patients in clinical remission at W10, 79.3% in the FIL200→FIL200 arm had a prolonged benefit (62.1% clinical remission; 17.2% MCS response) vs 44.4% in the FIL200→PBO arm (13.9% clinical remission; 30.6% MCS response). In the FIL200→FIL200 arm, 82.0% of patients with prolonged benefit at W58 had IBDQ remission at W58 (Table).

Table. Proportion of patients with prolonged benefit at W58 and proportion of patients in IBDQ remission at W58 among those with prolonged benefit at W58.

Conclusion

After a year of FIL200 treatment, two-thirds of patients who were in clinical remission or had an MCS response at W10, and ~80% who were in clinical remission at W10, had a prolonged benefit.

References

Feagan BG et al. Lancet 2021;397:2372–84.

Disclosure

DL has received consulting, advisory board and transport fees from AbbVie, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, Prometheus, Roche and Takeda.
AS has received grant support from AbbVie; and consulting or speaker fees from AbbVie, Dr. Falk Pharma, Galapagos, Janssen Pharmaceuticals, MSD, Pfizer, Takeda and Tillotts Pharma.
TK has served as a speaker, a consultant or an advisory board member for AbbVie, Activaid, Ajinomoto Bio-Pharma, Alfresa Pharma, Asahi Kasei Medical, Astellas Pharma, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eisai, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, JIMRO, JMDC, Kissei, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, Thermo Fisher Scientific and Zeria Pharmaceutical; and has received research funding from AbbVie, Alfresa Pharma, Asahi Kasei Medical, EA Pharma, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Sekisui Medical, Thermo Fisher Scientific and Zeria Pharmaceutical.
TM reports personal fees from AbbVie, EA Pharma, Mitsubishi Tanabe Pharma and Takeda; and grant support from Mitsubishi Tanabe Pharma and Nippon Kayaku.
AO, MF and AdH are employees and shareholders of Galapagos NV.
CJ is a contractor at Galapagos NV.
SV reports grants from AbbVie, Galapagos, J&J, Pfizer and Takeda; consulting and/or speaker fees from AbbVie, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia Biologics, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, CvasThera, Cytoki Pharma, Dr Falk Pharma, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance Biopharma, Tillotts Pharma and Zealand Pharma.
The SELECTION trial was sponsored by Gilead Sciences Inc. Galapagos NV was a collaborator for the SELECTION trial and funded this analysis.
Medical writing support for the development of this abstract was provided by Elvi Nimali, MBiochem, of PharmaGenesis London, London, UK, and was funded by Galapagos NV.