5 abstracts awarded at UEG WEEK 2023
The annual international congress took place as a hybrid event in Copenhaguen and online during 14-16 October with over 11,000 participants.
Resmetirom can lead to the resolution of non-alcoholic steatohepatitis and improve liver fibrosis1
According to 52-week data from the phase 3 MAESTRO-NASH clinical trial, Resmetirom, administered at daily doses of 80-100 mg is effective and safe for patients with NASH and liver fibrosis. Resmetirom is a selective beta thyroid receptor agonist designed to treat the underlying causes of NASH in the liver, and the MAESTRO-NASH study is an ongoing 54-month trial testing this mechanism of action.
The study's primary endpoints were resolution of NASH without worsening fibrosis and improvement of at least one stage of fibrosis without worsening NASH activity. The results showed that resolution of NASH was achieved in 26% of patients treated with 80 mg Resmetirom and 30% of patients treated with 100 mg, while improvement of fibrosis was reported in 24% of patients on 80 mg and 26% of patients on 100 mg.
Positive effects also occurred on secondary endpoints such as LDL-cholesterol reduction at 24 weeks. Adverse events were similar between treatment groups, with diarrhoea and nausea being the most common side effects. Resmetirom appears to be well tolerated. This ongoing research could represent a possible therapy to prevent progression to cirrhosis and/or advanced liver disease, offering the first medical treatment option for NASH.
Computer-aided detection system outperforms endoscopists in histology2
A groundbreaking clinical study revealed that Computer Aided Detection (CADe) systems can detect extra colorectal polyps undetected by endoscopists. Early detection of colorectal cancer can improve the chances of 5-year survival, but only about 40% of colorectal cancer cases are detected at this early stage.
Therefore, in light of improvements in the detection of colorectal polyps with CADe, investigators initiated the innovative CAD-ARTIPOD [Clinical vAliDation of ARTificial Intelligence in POlyp Detection] study to clinically test a new multi-platform CADe in nine European centres.
This prospective multicentre study is innovative because it allowed the performance of both CADe and endoscopists to be evaluated. The CADe system was designed by combining a convolutional neural network with a recurrent neural network for the detection of colorectal polyps trained in all imaging modalities. Participating endoscopists were unaware of the CADe results, while a second trained observer evaluated and classified the CADe results in real time. If a polyp detected by the CADe was not detected by the endoscopists, they were informed to confirm the discovery.
Of the 2141 polyps collected from 946 patients, the sensitivity of CADe was 0.946, compared to 0.961 for endoscopists. Therefore, the main endpoint of superiority between CADe and endoscopists was not achieved. However, the CADe detected 3.7% more polyps that had escaped the endoscopists.
Considering histology as the diagnostic standard, CADe outperformed endoscopists with a sensitivity of 0.96 compared to 0.95 (P<0.05), with a 5% higher detection rate. The detection rate of baseline polyps increased from 0.47 to 0.70 (odds ratio [OR]: 2.76; 95% confidence interval [CI]: 2.26-3.37) during the study, while the detection rate of adenomas increased from 0.38 at baseline to 0.50 (OR: 1.52; 95% CI: 1.26-1.85).
Given the high non-detection rate of reference standard colonoscopy, the objective evaluations provided by CADe systems offer the potential for earlier detection of cancerous polyps.
Long-term treatment with mirikizumab is effective and safe for moderate to severe ulcerative colitis3
Mirikizumab is a humanised IgG4 monoclonal antibody that binds to the p19 subunit of interleukin 23 and is part of a three-phase clinical trial programme called LUCENT.
The results obtained in this phase of the study (LUCENT-3) showed that mirikizumab maintained long-term efficacy and safety in patients who had responded positively to treatment by week 52. During the 104-week long-term treatment with mirikizumab, most patients showed clinical, endoscopic, histological and symptomatic improvements. These improvements included a reduction in symptoms such as frequency of evacuations, disappearance of blood in stool, and clinical remission.
The data showed that long-term treatment with mirikizumab was effective both for patients who had a positive response to treatment by week 52, and for those who had achieved remission by the same stage. Furthermore, no new safety signals emerged and no deaths were reported. The rate of treatment discontinuations due to adverse events was low, and serious adverse effects were reported in only a small percentage of patients.
In conclusion, long-term treatment with mirikizumab appears to be a viable option for patients with moderate-severe UC who did not respond positively to previous treatments. The drug offers clinical, endoscopic, histological and symptomatic benefits in this complex therapeutic area.
Surgery may not be the answer to reducing the risk of oesophageal adenocarcinoma in patients with Barrett's oesophagus4
A large population study revealed that anti-reflux surgery is not superior to anti-reflux drug therapy in preventing adenocarcinoma-type oesophageal cancer in patients with Barrett's oesophagus (BO).
Anti-reflux surgery had been considered as a potential preventive measure to reduce the risk of developing oesophageal cancer, as it was found to be at least as effective as anti-reflux medication in controlling the main risk factors of adenocarcinoma-type oesophageal cancer. However, an in-depth study compared the results between patients with BO who had undergone anti-reflux surgery and those who had used anti-reflux drug therapy.
The patients included in the study were from four countries and had a diagnosis of BO. The follow-up period was 32 years. During this long period, the results showed that patients who had undergone anti-reflux surgery did not have a reduced risk of developing oesophageal cancer compared to those who had used anti-reflux drug therapy, but on the contrary, the risk was increased. Moreover, the risk increased as the follow-up period was prolonged.
In summary, the study showed that, among patients with Barrett's oesophagus, antireflux surgery does not result in a reduced risk of developing adenocarcinoma-type oesophageal cancer compared to antireflux drug therapy. On the contrary, it appears that the risk increases over time among those who have undergone surgery.
Oncogenic GNAS and KRAS signalling drive dysplasia in an iPSC-derived organoid model for cystic pancreatic neoplasia5
A new study found that the GNASR201C mutation promotes early dysplasia formation and amplifies the effects of the KRASG12D mutation.
Intraductal papillary mucinous neoplasms (IPMNs) are cystic neoplasms of the pancreatic duct that can evolve into invasive adenocarcinomas. These neoplasms often have activating mutations in the guanine nucleotide binding protein, stimulant alpha (GNAS) and/or in the Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) gene, but the interactions and communications between these mutations are poorly understood.
The researchers used induced pluripotent stem cells (iPSCs). They investigated both mutations using a porcine urinary bladder model to monitor neoplasm formation.
At 2 weeks post-transplantation, all transplants showed the presence of cytokeratin 7- and 19-positive pancreatic ductal structures, demonstrating a robust cystic phenotype mainly attributable to GNASR201C, which remained stable for 8 weeks. Induction of KRASG12D over the course of 6 weeks resulted in an enlargement of duct luminosity, an effect that was more evident when GNASR201C was present. In addition, significant GNASR201C-dependent expression of mucin 2, which is associated with the intestinal IPMN subtype, was observed.
Quantitative analysis of dysplastic ductal structures revealed increased low-grade dysplasia caused by both KRASG12D and GNASR201C. However, the combination of both mutations was associated with a significant increase in the number of high-grade dysplastic ductal structures. Proliferation was observed in these ductal structures, mainly driven by GNASR201C.
KRASG12D significantly increased the number of p21-positive nuclei, indicative of increased proliferation, whereas a double mutation background of KRASG12D and GNASR201C reduced this effect, indicating a decrease in oncogene-induced senescence (OIS).
The key finding is that GNASR201C influences early dysplasia formation and amplifies KRASG12D-driven dysplasia, particularly in high-grade cases. Furthermore, the increased proliferation and reduced senescence in this setting suggest that GNASR201C might circumvent oncogene-induced senescence. This unique model of patient-derived iPSCs offers valuable insights into the mechanics underlying IPMN formation and its evolution towards invasiveness.
- Schattenberg J, et al. A randomised controlled phase 3 trial of resmetirom in non-alcoholic steatohepatitis: 52-week data rom MAESTRO-NASH. Presented at UEG Week 2023 Congress; 15 October 2023; Copenhagen, Demark.
- Sinonquel P, et al. Clinical validation of a computer-aided detection model for colorectal polyp detection (CAD-ARTIPOD) using a second observer and real-time unblinding. Presented at UEG Week 2023 Congress; 15 October 2023; Copenhagen, Demark.
- Sands BE, et al. Two-year efficacy and safety or mirikizumab following 104 weeks of continuous treatment: Interim results from the LUCENT-3 open-label extension. Presented at UEG Week 2023 Congress; 15 October 2023; Copenhagen, Demark.
- Hardvik Åkerström J, et al. Antireflux surgery versus antireflux medication and risk of esophageal adenocarcinoma in patients with Barrett’s esophagus. Presented at UEG Week 2023 Congress; 16 October 2023; Copenhagen, Demark.
- Lopatta P, et al. Oncogenic GNAS and KRAS signaling collectively drive dysplasia in an IPSC-derived organoid model for cystic pancreatic neoplasia. Presented at UEG Week 2023 Congress; 16 October 2023; Copenhagen, Demark.