Introduction

Antibiotic resistance in H. pylori (Hp) is becoming a more significant challenge in the management of Hp infection. Resistance surveillance is recommended to guide clinicians in the most appropriate therapy in a given population. Molecular methods offer a more rapid alternative for the detection of Hp resistance to antibiotics than traditional culture-based methods.

Aims & Methods

To evaluate the diagnostic accuracy of molecular-based clarithromycin susceptibility testing in Hp compared to culture and E-test in the Irish healthcare setting.
Following ethical approval and informed consent, adults were recruited prospectively from 2 centres (Tallaght University Hospital and Letterkenny University Hospital, Ireland), regardless of previous Hp treatment history. During routine gastroscopy, subjects had two supplementary biopsies (1 antrum and 1 corpus) taken for Hp culturing and DNA extraction. After successful Hp growth, clarithromycin susceptibility testing was performed by the Etest (Biomerieux) method and resistance was determined according to EUCAST 2023 guidelines. DNA was then extracted from biopsies and underwent PCR using the RIDA®GENE Helicobacter pylori assay (R-Biopharm AG, Germany) for detection of Hp and clarithromycin resistance-associated point mutations (A2146C, A2146G and A2147G).

Results

In all, samples from 191 culture-positive patients (mean age 48.4 ± 15.3 years; 45.0% (N=86) female) were analysed. The rates of clarithromycin resistance detected by culture-based and molecular methods were 49.2% (N=94/191) and 38.7% (N=74/191), respectively (P=0.05; Fisher’s exact test). Results were in agreement between both methods in 84.3% (N=161/191) of cases. The sensitivity and specificity of the Ridagene assay compared to culture for the detection of clarithromycin resistance were 74.2% (95% CI: 64.4-82.6%) and 94.7% (95% CI: 88.0-98.3%), respectively. The positive predictive value was 93.5% (95% CI: 85.5-97.9%) and the negative predictive value was 78.1% (95% CI: 69.4-85.3%).

Conclusion

While the Ridagene assay was easy to use and more rapid than Hp culture, the low sensitivity compared to culture in our cohort may limit its use to cases where culture-based methods are unsuccessful. Further studies are required to characterise the full spectrum of clarithromycin resistance mechanisms present in our population.

Introduction

Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious in inducing clinical response at Week(W) 12 and maintaining clinical remission through W52 in patients with moderately-to-severely active Crohn’s disease (CD) as shown in the phase 3 treat-through trial VIVID-1 (NCT03926130).¹ Here, we present analysis of maintenance outcomes through W52 for Patient-Reported Outcome (PRO) clinical responders and nonresponders at W12.

Aims & Methods

The analysis set includes patients randomized to mirikizumab at baseline, who did or did not achieve PRO clinical response at W12 after intravenous (IV) induction treatment (900 mg mirikizumab IV every 4 weeks [Q4W]) before entering subcutaneous (SC) maintenance treatment (300 mg mirikizumab SC Q4W). Descriptive statistics are used to summarize the data, applying nonresponder imputation for missing binary endpoints. As a treat-through study, no rerandomization was applied.

Results

From a total of 551 patients who entered SC maintenance treatment, baseline characteristics of age, duration of CD, and baseline Crohn’s Disease Activity Index (CDAI) were similar between W12 PRO responders (n=402, 73.0%) and W12 PRO nonresponders (n=149, 27.0%). PRO responders at W12 had a higher objective inflammatory burden at baseline (faecal calprotectin, c-reactive protein, and Simple Endoscopic Score-CD), whereas concomitant or prior medication usage was similar between the groups. For W12 PRO responders, SC mirikizumab treatment from W12 to W52 resulted in an increase in CDAI clinical remission from 52.2% to 65.4%, PRO clinical remission from 53.2% to 65.4%, and endoscopic response from 35.1% to 54.7%, respectively (Table 1). Among W12 PRO nonresponders, PRO response was achieved by 39.6% at W16, 45.6% at W20, 44.3% at W24, and 56.4% at W52 with continued mirikizumab SC treatment, while CDAI clinical remission and PRO clinical remission were achieved by 33.6% and 31.5% at W52, respectively. Endoscopic response increased from 30.2% at W12 to 40.3% at W52 among W12 PRO nonresponders (Table 1).

Conclusion

Subcutaneous mirikizumab maintenance treatment over 40 weeks leads to incremental and sustained improvements in rates of clinical and endoscopic response regardless of PRO clinical response status after induction. A substantial proportion of clinical nonresponders at W12 improved early during maintenance treatment suggesting continued treatment with mirikizumab can be beneficial and lead to long-term response.

References

1. Ferrante, Marc et al. Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study. Lancet. 2024;404(10470):2423-2436. doi:10.1016/S0140-6736(24)01762-8

Introduction

Intragastric balloon (IGB) is a minimally invasive intervention used for obese patients who do not achieve adequate weight loss with standard medical therapy (SMT), which includes lifestyle interventions with or without pharmacological treatment. It is also an option for individuals who do not meet the criteria for bariatric surgery or choose not to undergo it. Despite its growing use, there is little data on the short and long-term effectiveness of IGB compared to SMT in randomized controlled trials (RCTs).

Aims & Methods

This systematic review and meta-analysis aimed to compare the efficacy of IGB therapy for at least six months versus SMT in the treatment of obesity, assessing outcomes at 6, 9, and 12 months. A comprehensive literature search was conducted in the MEDLINE, EMBASE, and Cochrane Library databases. The primary outcome was the percentage of excess weight loss (%EWL), while secondary outcomes included absolute weight loss (AWL), percentage of total weight loss (%TWL), and body mass index reduction (BMIR). We calculated mean differences (MD) with 95% confidence intervals (CI) for continuous outcomes. Meta-regression was performed using baseline body mass index (BMI) as a covariate, and subgroup analyses were conducted based on IGB type, baseline BMI, and pharmacological therapy in the SMT group.

Results

A total of 15 RCTs, including 1,961 patients, were included. Compared to SMT, IGB therapy resulted in significantly greater %EWL at 6 months (MD 16.80%; 95% CI [9.22%; 24.38%]), 9 months (MD 14.36%; 95% CI [7.67%; 21.04%]), and 12 months (MD 13.10%; 95% CI [10.43%; 15.77%]). IGB was also superior in AWL, %TWL, and BMIR across all time points (Table 1). Subgroup analyses revealed that results remained consistent regardless of pharmacological therapy use in the SMT group (p=0.77). The Orbera balloon showed superior %TWL at 6 months (p<0.01) and AWL at 6 months (test for subgroup differences with p=0.01), while the Spatz3 balloon demonstrated better %TWL at 9 months (p<0.01). Studies with a baseline BMI >40 kg/m² had significantly greater %TWL at 6 months (p=0.04) and AWL at 6 months (p<0.01) than those with BMI ≤40 kg/m². Meta-regression analysis indicated that higher baseline BMI was associated with greater AWL and BMIR at 6 months.

Conclusion

IGB therapy was significantly more effective than SMT, even when pharmacological therapy was included, leading to superior weight loss outcomes at 6, 9, and 12 months.

Table 1. Summary of findings.

References

1- Abu Dayyeh, Barham K, et al. Lancet. 2021.

2- Chan, Daniel L., et al. Obesity Surgery. 2021.

3- Coffin, B, et al. Obes Surg. 2017.

4- Courcoulas, et al. Int Journal of Obesity. 2017.

5- Farina, Maria Grazia, et al. Obes Surg. 2012.

6- Fuller, et al. Obes Bio and Int Physiology. 2013.

7- Gómez, V, et al. Obesity. 2016.

8- Hollenbach, M, et al. Digestion. 2024.

9- Kashani, et al. SN Comp Clinical Med. 2022.

10- Konopko-Zubrzycka, et al. J Clin Endoc Metab. 2009.

11- Lee, YM, et al. Gastrointest Endosc. 2012.

12- Mohammed, et al. Trends Med Res. 2014.

13- Ponce, J, et al. Surg Obes Relat Dis. 2015.

14- Sullivan, S, et al. Surg Obes Relat Dis. 2018.

15- Vicente, M, et al. Surgical Endoscopy. 2020.

Introduction

A few studies have suggested the association between Helicobacter pylori (HP) infection and atherosclerosis including coronary heart disease and ischemic stroke. However, the effect of HP eradication on ischemic stroke has not been well evaluated, so far.

Aims & Methods

The objective of this study was twofold: (1) to compare the risks of ischemic stroke and cerebral atherosclerosis as a pre-clinical stage of ischemic stroke according to HP eradication status among HP-infected patients (HP-eradicated vs. HP-non-eradicated), and (2) to compare these risks in HP-eradicated patients to those in HP-naive subjects. We conducted a prospective observational cohort study. HP tests with gastroscopy were performed in Seoul National University Bundang Hospital from May 2003 to February 2023. HP infection was diagnosed through ≥1 findings of histopathology, rapid urease test or culture. Propensity score matching for each group was calculated with relevant covariates, including age, sex, alcohol, smoking, hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, and aspirin intake. Patients in HP-eradicated group were matched in a 2:1 and 1:1 ratio with patients in HP-non-eradicated and HP-naive groups, respectively. Ischemic stroke and cerebral atherosclerosis were confirmed by brain MRI. The risk of ischemic stroke and cerebral atherosclerosis was analyzed using Cox-proportional hazard regression analysis.

Results

A total of 8,025 patients were included. After 2:1 matching, HP-eradicated group comprised 2,030 patients and HP-non-eradicated group comprised 1,015 patients(Figure). In a Cox-proportional hazard analysis, HP-eradicated group was associated with a significantly lower risk of ischemic stroke and cerebral atherosclerosis (hazard ratio [HR] 0.651, 95% confidence interval [CI] 0.451-0.941, p=0.026) (Table). In a second analysis, we included 2,064 patients with HP-eradicated and 2,064 HP-naive subjects, after PSM at a 1:1 ratio. In a Cox-proportional hazard analysis, the risk of ischemic stroke and cerebral atherosclerosis was not significantly different between the two groups (HR 1.109, 95% CI 0.777-1.584, p=0.569).

Conclusion

This large prospective observational cohort study suggested that HP eradication has preventive effect on the ischemic stroke and cerebral atherosclerosis.

Introduction

Gastric cancer is a malignant tumor that seriously endangers human physical and mental health worldwide. H. pylori infection is considered to be the major cause of gastric cancer. Differences in clinical outcomes after H. pylori infection may be related to bacterial virulence. Thioredoxin-1 (Trx1) and Arginase (RocF) expressed by H. pylori were found to be closely related to its pathogenicity and promoted gastric cancer pathogenesis in our previous study.

Aims & Methods

To explore whether Helicobacter pylori Trx1 and RocF can be used as a marker of highly pathogenic Helicobacter pylori and its pathogenesis. We investigated the expression level of H. pylori trx1 and H. pylori rocF in human gastric antrum tissues using reverse transcription and quantitative real-time PCR (RT-qPCR) and clarified the clinical application value of trx1 and rocF for screening highly pathogenic H. pylori. The pathogenic mechanism of Trx1 were further explored by RNA-seq of GES-1 cells co-cultured with trx1 high or low expressing H. pylori. Differentially expressed genes and signaling pathways were validated by RT-qPCR, Enzyme-linked immunosorbent assay (ELISA), western blot, immunohistochemistry and immunofluorescence. We also assessed the adherence of trx1 high and low expressing H. pylori to GES-1 cells.

Results

We found that H. pylori trx1 and H. pylori rocF were more significantly expressed in the gastric cancer and peptic ulcer group than that in the gastritis group and the parallel diagnosis of H. pylori trx1 and H. pylori rocF had high sensitivity. Trx1 high expressing H. pylori had stronger adhesion ability to GES-1 cells and upregulated the interleukin (IL) 23A/Nuclear factor κappaB (NF-κB)/IL17A, IL6,IL8 pathway.

Conclusion

In conclusion, H. pylori trx1 and H. pylori rocF can be used in clinical screening of highly pathogenic H. pylori and predicting the outcome of H. pylori infection. trx1 high expressing H. pylori enhances the adhesion capacity and promotes the development of gastric diseases by upregulating the NF-κB signaling pathway and related inflammatory cytokines.

References

1. Sung H.,Ferlay J.,Siegel R.L.,Laversanne M.,Soerjomataram I.,Jemal A., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin.71, 209-249.
2. Schottker B., Adamu M.A., Weck M.N. and Brenner H. (2012) Helicobacter pylori infection is strongly associated with gastric and duodenal ulcers in a large prospective study. Clin Gastroenterol Hepatol.10, 487-493.

Disclosure

The authors declare that there is no competing interests associated with the manuscript.

Introduction

While three JAK inhibitors are now available in Ulcerative Colitis (UC), no direct comparison exists between these drugs making difficult the hierarchization of these therapeutic options.

Aims & Methods

We performed a systematic review and network meta-analysis to compare the short and long-term efficacy of the three available JAK inhibitors (JAKi) (Tofacitinib/TOFA, filgotinib/FILGO, upadacitinib/UPA) in patients with moderat-to-severe UC.
We performed a systematic review and network meta-analysis (PRISMAguidelines) of randomized controlled trials (including post-hoc analyses) conducted in adults, evaluating the efficacy of JAKi in moderate-to-severe UC.
The outcome mesures were 1) steroid-free clinical remission (CFREM) after induction therapy (partial Mayo score ≤ 2), 2) CFREM with endoscopic improvement (endoscopic Mayo score ≤ 1) after induction therapy, 3) CFREM at one year among induction-responders, 4) CFREM at one year among patients in clinical remission after induction.
The network meta-analysis was carried out according to a random effects model. The results are presented as relative risk (RR) with 95% confidence interval. The risk of bias of the studies was assessed according to the Cochrane risk-of-bias tool for randomized trials and overall statistical heterogeneity between studies was assessed using τ .
The SUCRA ranking method (surface under the cumulative ranking) was used to rank the treatments.

Results

Nine studies were included in this network meta-analysis, including a total of 2015 patients.
TOFA 10mg bid, FILGO 200 mg qd and UPA 45mg qd were more effective than placebo to induce CFREM and CFREM with endoscopic improvement. Side-by-side comparisons between JAKi found a higher efficacy of UPA 45 mg qd versus FILGO 200 mg qd (RR=0.22[0.10; 0.45]) for induction but no other significant difference between JAKi. SUCRA ranking hierarchizes induction therapies as following : UPA 45 mg qd (0.99), TOFA 10mg bid (0.75), FILGO 200 mg qd (0.27) and placebo (0.01).
Among induction-responders, all JAKi maintenance regimen (TOFA 10mg bid, TOFA 5mg, bid, FILGO 200mg qd, FILGO 100 mg qd, UPA 30 mg qd, UPA 15 mg qd) were more effective than placebo to achieve CFREM at one year with the following SUCRA ranking : UPA 30mg qd (0.85), TOFA 10mg bid (0.80), FILGO 200 mg qd (0.64), TOFA 5mg bid (0.56), UPA 15 mg (0.44), and placebo (0.01).
Among patients in CFREM after induction phase, all JAKi maintenance regimen (TOFA 10mg bid, TOFA 5mg, bid, FILGO 200mg qd, FILGO 100 mg qd, UPA 30 mg qd, UPA 15 mg qd) were more effective than placebo to achieve CFREM at one year with a different ranking (SUCRA) : TOFA 10 mg bid (0.84), FILGO 200 mg bid (0.74), TOFA (5mg bid) (0 .66), UPA 30mg qd (0.63), UPA 15 mg (0.44) and placebo (0.09).

Conclusion

While this network meta-analysis confirms the efficacy of JAKi to induce and maintain CFREM in moderate-to-severe UC, UPA seems to be the most effective JAKi to induce and maintain CFREM. However, once CFREM achieved after induction, continuing the same dose than during induction such as TOFA (10mg bid) or FILGO 200 mg seems to be more effective than reducing the dose (UPA 30 mg or UPA 15 mg) to maintain remission highlighting the dose-efficacy relationship of JAKi.

Disclosure

Consulting fees from: Abbvie, Amgen, Arena, Biocon, Biogen, Celltrion Healthcare, CTMA, Ferring, Galapagos/AlfaSigma, GutyCare/Resilience Janssen, Lilly, MSD, Nexbiome, Pfizer, Roche, Sandoz, Takeda et Tillotts
Lecture fees from: Abbvie, Amgen, Biogen, Celltrion Healthcare Galapagos/AlfaSigma, Ferring, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Norgine, Pfizer, Roche, Takeda, Tillotts and Vifor Pharma
Research grants/fundings from: Abbvie, Celltrion Healthcare, Janssen, Lessaffre, Lilly, Pfizer, Sandoz and Takeda