Introduction

The TOGAS consortium (TOwards GAstric cancer Screening) was established to explore effective gastric cancer screening strategies within Europe. One key method involves the detection and eradication of Helicobacter pylori (H. pylori), the leading causative agent of gastric cancer. In Western Europe, infection rates are higher among males, smokers, and individuals of lower socioeconomic status—groups that tend to engage less with preventive health services.

Aims & Methods

This pilot study aimed to determine whether targeted screening in high-risk occupational settings improves participation and outcomes compared to population-based screening via general practice.
Key outcome measures included;

1. Response rate
2. Prevalence of the infection
3. Treatment effectiveness

This prospective pilot study recruited individuals aged 30–34 years from January 2024 to March 2025. Participants were invited either through general practices (general population group, GP) or through two occupational screening programs (targeted group, TG) representing higher-risk, male-dominated workforces: the Irish Defence Forces and Construction Workers Health Trust. Exclusion criteria included prior H. pylori treatment or gastrectomy. All participants underwent serologic screening (BIOHIT H. pylori IgG antibody). The TG was offered initial on-site screening at their workplace; the GP group attended a local hospital. All seropositive individuals were offered confirmatory 13-C urea breath testing (Richen IR Force 200) in a local hospital. Confirmed cases were offered a 10-day regimen of PYLERA (Metronidazole/Tetracycline/Bismuth subcitrate) with Esomeprazole 40 mg BD. Eradication was assessed ≥6 weeks post-treatment. Response rates, demographics, infection prevalence, and treatment outcomes were analyzed using Mann-Whitney U and Chi² tests (significance p < 0.05).

Results

3030 individuals were invited for screening: 2824 in the GP group(GPG), 206 in the TG. Key demographics and risk factors of each group are shown in Table 1. The invitation response and participation rates were significantly higher in the TG versus the GPG (31% v’s 14%; p < 0.001, 30% v’s 14% p <0.00, respectively). H. pylori seroprevalence rates were similar between groups: 18% (11/60) in the TG, 19% (64/333) in the GPG (p<0.70). Confirmatory 13-C UBT was completed in 91% (10/11) of those who tested positive in the TG and 98% (63/64) of the GPG. Overall, ‘true’ prevalence rates based on serology & confirmatory 13-C UBT results were 10%(6/59) in the TG v’s 14% (44/325) in the GPG(p = 0.47). Treatment adherence exceeded 90% in both groups, with 100% adherence in the TG and 90% in the GPG. Among those who completed post-treatment testing (n=37), eradication was achieved in 100% of the TG (2/2) and 89% of the GPG (31/35).

Table 1 Basic Demographics by Group

	Targeted group	General population
Gender, male	97%	33%
Median age, years	31	32
Smoking status Current/previous Non-smoker	41% (24) 59% (34)	34% (137) 66% (266)
Socioeconomic status(self-rated) Higher Middle Lower Prefer not to answer	69% (40/58) 22% (13/58) 0 9% (5/58)	85% (337/397) 11% (42/397) 0% (2/397) 4% (16/397)
Family history of H.pylori infection	3% (2)	9% (36)

Conclusion

Targeted occupational screening in high-risk populations demonstrated superior response and engagement rates compared to general practice-based screening. These early results suggest this approach may be a more effective and resource-conscious strategy in low-to-intermediate risk countries and merit further evaluation in broader implementation efforts.

References

1. Teo CH, Ng CJ, Booth A, White A. Barriers and facilitators to health screening in men: A systematic review. Soc Sci Med. 2016 Sep;165:168-176. doi: 10.1016/j.socscimed.2016.07.023. Epub 2016 Aug 1. PMID: 27511617. 5.
2. Lou L, Wang L, Zhang Y, et al. Sex difference in incidence of gastric cancer: an international comparative study based on the Global Burden of Disease Study 2017.BMJ Open 2020;10:e033323. doi: 10.1136/bmjopen-2019-033323
3. Salmani H, Ahmadi M, Shahrokhi N. The Impact of Mobile Health on Cancer Screening: A Systematic Review. Cancer Informatics. 2020;19. doi:10.1177/1176935120954191
4. CSO. (2023, May 30). Employment, Occupation, Industry and Commuting - CSO -Central Statistics Office. https://www.cso.ie/en/releasesandpublications/ep/pcpsr/censusofpopulation2022- summaryresults/employmentoccupationindustryandcommuting/

Disclosure

Dr. Deane reports receipt of research funding support from EU4 Health grant GA number: 101101252. Receipt of ​13-C Urea Breath Test bags for this study was provided for by Richen - Dr Deane was the winner of the Richen Global ​Research Competition 2023

Introduction

Irritable bowel syndrome (IBS), which affects between 5 and 10% of the population according to the Rome III or IV diagnostic criteria, manifests as chronic abdominal pain associated with altered bowel transit. Moderate or severe IBS significantly impair the quality of life of patients, who are often dissatisfied with conventional treatments. In search of more effective solutions, many are turning to complementary and alternative approaches, such as hypnotherapy, whose effectiveness is well-established. Among these approaches, osteopathy, adopted by nearly 40% of patients in France, attracts growing interest. Single-centre studies with small sample sizes (30 to 40 patients) have reported promising but miscellaneous results, suggesting an improvement in symptoms and an effect on rectal sensitivity (1), or a transient effect on the severity of IBS (2).

Aims & Methods

Our study aims to evaluate the efficacy of visceral osteopathy on the severity of IBS symptoms in a French multicentre study. The trial, conducted as part of the 2015 National Hospital Clinical Research Program (PHRCN-PHRC-15-294), included adult patients suffering from IBS according to Rome III criteria and with moderate or severe IBS (IBS-SSS of 175 to 500 points at baseline). Patients were randomised into two groups: one with visceral osteopathy (three sessions performed over one month, two weeks apart) and one with placebo manipulation performed by the same osteopaths. Clinical characteristics (age, gender, BMI, IBS subtype according to bowel movements), anxiety (Spielberger State-Trait Anxiety Inventory, STAI-1 and STAI-2) and depression (Beck Depression Inventory or BDI II) levels, quality of life (IBS-QOL, ranging from 0 to 100, with 100 corresponding to the best quality of life), and IBS severity (IBS-SSS) were recorded. The primary objective of the study was the improvement in the IBS-SSS severity score at 2 months (1 month after the end of osteopathy). The effects on anxiety and depression levels as well as on quality of life were secondary objectives. The number of subjects to be included was calculated at 210 patients.

Results

Six centres included a total of 156 patients* (78 per group): mean age of 46 (± 15) years, 73% of women, 60% with IBS-C, 17% with IBS-D, 15% with IBS-M, and 8% with IBS-U. The mean IBS-SSS severity score was 336 (± 66) points (27.1% moderate severity and 72.9% severe with IBS-SSS > 300), with no difference between the two groups. Before inclusion, 61% of patients felt that osteopathy would be effective for their condition. At 2 months, the absolute decrease in the severity score (primary endpoint) was similar in both groups (52.4 ± 97.6 vs. 48.6 ± 98.9 points, p-value = 0.975), suggesting a placebo effect, as were the state-trait anxiety levels and quality of life (secondary endpoints).
* The monitoring committee terminated the study after a futility analysis on the first 156 patients because the study message could not be changed by including additional patients out of a planned total of 210.

Conclusion

In this first randomised multicentre study, visceral osteopathy was no more effective than a placebo manipulation in improving the severity of IBS, psychological comorbidities, or quality of life.

References

(1) Attali et al. Treatment of refractory irritable bowel syndrome with visceral osteopathy: Short-term and long-term results of a randomized trial. Journal of Digestive Diseases 2013; 14; 654–661. doi: 10.1111/1751-2980.12098
(2) Florance et al. Osteopathy improves the severity of irritable bowel syndrome: a pilot randomized sham-controlled study. European Journal of Gastroenterology & Hepatology 2012 ; 24 (8) : p 944-949. DOI: 10.1097/MEG.0b013e3283543eb7

Disclosure

Nothing to disclose

Introduction

Current treatment options for IBD are limited by low clinical remission rates and loss of response. Most therapies target single pathogenic pathways and while combinations of biologics targeting different pathogenic cytokines can increase clinical remission rates, dosing schedules are inconvenient. JAK inhibitors, target multiple cytokine pathways, but are limited by safety concerns.
Salt-inducible kinases (SIKs) are a subfamily of serine/threonine kinases in the AMP-activated protein kinase (AMPK) family and act as key regulators of immune cell signaling. SIK inhibitors have been shown to target multiple cytokine pathways.
Three SIK isoforms exist: SIK1, SIK2 and SIK3. SIK inhibitors targeting multiple isoforms have been investigated in clinical trials. Although there have been signals of activity in patients with ulcerative colitis and psoriasis, limited efficacy and safety concerns related to SIK1 and 2 inhibition have hampered their development.

Aims & Methods

We performed structure based drug design to identify highly potent and selective SIK3 inhibitors that could offerbest in class efficacy and safety for the treatment of various auto-immune diseases. Our effort led to to the discovery of 100s of compounds spanning SIK3 binding sites. Compounds were tested in protein and cell-based assays to evaluate potency and selectivity against SIK3 and in a phenotypic human whole blood TNFα assay. Lead optimization involving rigorous testing in safety and pharmacology panels, resulted in the selection of lead candidates that were tested in a variety of translational models to identify the most efficacious compounds. Human PK predictions were performed using non-clinical in vivo PK assessments and allometric scaling leading to the selection of the drug candidate, which entered GLP toxicology studies.

Results

O3R-5671 is a highly potent and specific SIK3 inhibitor with sub-nanomolar potency for SIK3 and low activity against SIK1 and 2 and over all human kinases. It demonstrated potent activity in a panel of human primary phenotypic cell assays inhibiting TNFα, IL-12, and IL-23 release in LPS-stimulated myeloid cells, and inhibiting TNFa release in LPS-stimulated human whole blood. O3R-5671 also inhibited activation of TCR-stimulated human primary T cells and induced IL-10 secretion from myeloid cells.
In vivo, O3R-5671 demonstrated dose-dependent activity in a mouse LPS challenge model, dose-dependent efficacy in two distinct mouse models of IBD, and dose-dependent efficacy in mouse models of IL-23-induced psoriasis and psoriatic arthritis. Cross-species PK and allometric scaling were used to predict O3R-5671’s human PK profile- which is expected to be conducive to potent SIK3 inhibition and clinical efficacy in patients with IBD.
O3R-5671 demonstrated a highly attractive profile in ADME and in vitro safety panels. Six-week GLP toxicity studies in rats and dogs established no observed adverse effect levels (NOAELs) which support dosing in humans with doses that are predicted to be pharmacologically active with a large safety margin.

Conclusion

O3R-5671 is a highly specific and potent SIK3 inhibitor that is predicted to have a flat PK profile in humans. These properties should allow O3R-5671 to apply strong drug pressure on SIK3 while sparing SIK1 and 2. This is expected to result in the inhibition of multiple pathogenic cytokines including TNFa and IL-23, both of which have been validated as IBD targets. A clinical trial is ongoing to establish the safety and PK profile of O3R-5671 and understand its effect on pharmacodynamic biomarkers.

Disclosure

All authors were employed by Galapagos who discovered O3R-5671 or Novalix, a CRO that was employed by Galapagos. Some authors are employed by Onco3R therapeutics, who are currently developing O3R-5671