Introduction

Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterized by corpus-restricted atrophy and pseudopyloric or intestinal metaplasia, associated with reduced hydrochloric acid and intrinsic factor production and heterogeneous clinical consequences. The aetiology of AAG is autoimmune, but the role of Helicobacter pylori (Hp) has been proposed, although not definitively proven. A possible antigenic crossreactivity with H+,K+-ATPase, the main autoantigen in AAG, has been reported and Hp seropositivity has been described in histologically Hp negative AAG. One study employed molecular biology techniques to characterize a cohort of AAG patients as definitively Hp naïve.

Aims & Methods

The aim was to assess the presence of Hp-related genes in corpus mucosa biopsies of pts with AAG and Hp-positive and negative ctr by using real-time PCR.
Single-centre, experimental molecular biology study on 55 pts with histologically diagnosed AAG, of whom at histology 52 were Hp negative (age 61.5, range 28-88 yrs, 75% F, 96.2% parietal cell (PCA) and 44.2% intrinsic factor antibodies (IFA) positive), while 3 were Hp positive (age 74,69,33 yrs; 1 F; all 3 PCA and 1 IFA positive). Ctr were 4 pts who underwent gastroscopy for non-ulcer dyspepsia, 2 with Hp-positive superficial antral gastritis (positive ctr), and 2 with a healthy stomach (negative ctr). Hp serology (ELISA or multiplex) was available from all pts. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue sections of corpus mucosa biopsies and real-time PCR was performed using specific probes for UreA, UreC, and CagA Hp related genes; 16sRNA and Beta2 microglobulin (B2M) specific probes were used as amplification ctr of bacterial and human DNA (real-time PCR cycle threshold (CT) >28<38).

Results

In 4(7.7%) of the 52 histologically Hp negative AAG pts, Hp-related genes were detected, in 4(7.7%) UreC, in 3(5.8%) UreA, and in 1(1.9%) CagA. All of them (3 F, aged 88,85,58,56 yrs) had positive Hp serology and PCA, only one was IFA-positive. The detectability of B2M and bacterial 16sRNA genes did not differ in UreC-positive or UreC-negative pts (B2M CT mean 29.6±1.2 for Ure-C positives vs 29.7±1.4 for Ure-C negatives, p=0.99; 16SrRNA gene CT mean 29.9±1.2 vs 29.4±1.2, p=0.27) indicating that the not-detectability of Hp-related genes was unrelated to reduced amounts of gastric bacterial or human DNA. Hp serology was positive in all 4 histologically Hp-negative AAG pts positive for UreC compared to 5/48(10.4%) UreC negative pts (p<0.0001) indicating previous exposure. PCA were present in all 4 UreC positive AAG pts compared to 46/48(95.8%) of UreC negatives (p=0.68). IFA positivity in UreC negatives was nearly 2x higher than that of UreC positives (45.8% vs 25%, p=0.42) without reaching significance. In 2/3 pts with histologically Hp-positive AAG, Hp-related genes could be detected; in the remaining patient, nor UreA, UreC neither CagA gene could be found (M, 69 yrs, no anemia, PCA-IFA-Hp serology positive).

Conclusion

In >90% of histologically Hp-negative and PCA or IFA positive AAG pts, Hp-related genes cannot be retrieved in the gastric mucosa. In 10% of these Hp-genes negative AAG pts, previous exposure to Hp can be testified by positive serology.
Hp-related genes can be detected in gastric biopsies in <10% of histologically Hp-negative AAG patients and positive Hp serology further confirms the role of Hp in this group.
These findings show that primary, Hp naive AAG is the more common type, but in a subset of pts, AAG seems to be secondary to Hp infection.

References

Lenti MV, Nature Rev Dis Primer 2020,
Lahner E, Dig Liv Dis 2019,
Annibale B, Helicobacter ,
Mini R, Clin Chem 2007,
Dottori L, UEGW 2023
Rugge M, Gut 2022

Introduction

A good bowel preparation for colonoscopy is fundamental to improve the quality of the examination, reduce procedural complications and achieve optimal polyp detection. Among possible strategies to enhance bowel preparation, visual booklets have been proposed with conflicting results. Therefore we aimed to perform a systematic review with meta-analysis of randomized controlled studies (RCT) to ascertain whether booklets may be useful in this setting.

Aims & Methods

Literature search was performed in July 2022, in main databases (PUBMED, SCOPUS, ScienceDirect, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov). only RCTs were selected. The primary outcome was the quality of bowel preparation. Further outcomes were the adenoma detection rate (ADR), number of polyps detected per patient, rate of cecal intubation, time of insertion and withdrawal, adverse events, willingness to repeat preparation and colonoscopy. We estimated odd ratios (OR) for dichotomous outcomes. mean differences (MD) or standardized mean differences (SMD) were used for continuous outcomes. We estimated heterogeneity among studies with the Chi2 (Cochran Q) and the I2 statistics. In case of high heterogeneity, a random effect model was used, otherwise a fixed effects model was preferred. All analyses were performed using RevMan version 5.4.1.

Results

Six studies were selected, enrolling overall 1755 patients (857 in the booklet and 898 in the control group). Adequate bowel preparation was achieved in the 86.7% (743 out of 857) of booklet preparation versus the 77.5% (696 out of 898) in the control group, with an OR of 2.31 in favour of booklet (95% CI 1.20-4.45, p = 0.01). Booklet was more effective than control in the transverse colon (MD = 0.37, 95% CI 0.01-0.72, p = 0.03), while no differences were found in right colon and left colon. In four studies a 4-L PEG-based preparation was used and the pooled analysis did not find any difference compared to controls, while when sodium phosphate and magnesium citrate or sodium phosphate or PEG were used, preparation with booklet was better than in controls (OR = 5.10, 95% CI 1.82-14.27, p = 0.002). Two studies were performed in inpatient setting, without difference between booklet and controls while in outpatients patients receiving booklets were better prepared than controls (OR = 7.13, 95% CI 5.39-9.45, p < 0.001). ADR was similar between the two groups, with an OR = 0.93 (95% CI 0.75-1.16, p = 0.53). The mean number of polyps per patient did not differ between the two groups (MD = 0.22, 95% CI -0.14-0.58, p = 0.23).

Conclusion

The present meta-analysis demonstrated that booklets are useful to enhance bowel preparation. Outpatients and non PEG-based preparations seem to benefit more from booklets, while no effect on ADR has been observed.

Clinical Case Summary

Management of bleeding GIST is challenging, especially in metastatic disease. Emergent surgery for bleeding GIST lesions has a high rate of morbility and mortality in comparison to elective procedures (1). A safe and accurate method to obtain a permanent hemostasis is needed. Several endoscopic procedures are available although with limited efficacy due to the complex neoangiogenesis of these tumours that remains out of reach of contact endoscopic techniques (2). EUS-guided therapy of bleeding GIST injecting cyanoacrylate or ethanol has been published. After one adverse event of spurting bleeding after EUS-guided injection of cyanoacryalte, our group first reported the EUS-guided coil puls cyanoacrylate injection therapy for bleeding GIST in two patients (3). We report our experience in five consecutive cases of bleeding GIST successfully treated under EUS-guidance (Table 1). Given the rich network of arteries in some cases, we aim to deploy coils into de tumor .
One adverse event was observed. An intratumoral bleeding after the punction of a 22G needle, successfully managed by EUS-guided deployment of a coil plus CYA. The clinical outcome in these five patients was uneventful until scheduled surgery was performed or palliative therapy in the fifth patient with a metastatic GIST with oncologic progression disease.

CASE	AGE	LOCALZATION SIZE OF THE ARTERY	CLINICAL PRESENTATION	EUS-GUIDED PROCEDURE NEEDLE CYANOACRYLATE/COILS	ADVERSE EVENTS	CLINICAL OUTCOME SCHEDULED SURGERY
1	82	Duodenal Bulb 2 mm	Recurrent melena Two unsuccessful endoscopic injection and clipping therapy	22 gauge 1 mL CYA	None	Uneventful 4 years
2	72	Fundus 5 mm	Hematemesis and hypovolemic shock	22 gauge 1 mL CYA 19 gauge 1 coil (6 mm/20cm long) 2 mL CYA	Bleeding after injection of 1 mL CYA Hemostasis after deployment of 1 coil and 2 mL CYA	Uventful 3 years
3	79	Fundus 4 mm	Hematemesis and hypovolemic shock	19 gauge 1 coil (6mm/14 mm long)	None	Uneventful
4	43	Fundus 3 mm	Melena	19 gauge 3 coils (3 mm/14cm long) 2 mL CYA	None	Uneventful 2 years
5	63	Body Metastatic GIST with oncologic progressiion Several 4 mm arteries	Hypovolemic shock	19 gauge 1 session: 5 coils (14mm/14 cm long) plus 2 mL CYA 2 session (anemia): 6 coils (6 mm/14 cm) plus 1 mL CYA	None	Uneventful on palliative care 6 weeks

EUS-guided therapy of bleeding GIST was effective in these five cases and could be another safe and accurate endoscopic procedure in bleeding GIST aiming to obtain hemostasis until scheduled surgical therapy is carried out or as palliative therapy. In these cases there were not observed recurrent bleeding in spite of a rich network of arterial vessels.

References

(1) Liu Q, Kong F, Zhou J, et al. Management of hemorrhage in gastrointestinal stromal tumors: a review. Cancer Manag Res. 2018;10:735-43.
(2) Venezia G, Asnaghi G, Manca A, et al. Successful use of Hemospray as a bridge to surgery in life-threatening bleeding from a gastrointestinal stromal tumor of the stomach. Endoscopy 2016;48:E232-E233.
(3) Romero-Castro R, Jimenez-Garcia VA, Irisawa A, et al. Endoscopic ultrasound-guided angiotherapy in bleeding gastrointestinal stromal tumors with coil deployment and cyanoacrylate injection. Endoscopy. 2021;53(4):E124-E5.

Disclosure

Rafael Romero Castro is consultant to Cook Medical since 28th, 2023.

Introduction

Ustekinumab, an interleukin (IL) 12/23 inhibitor is a biologic used to treat inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Clinical and real-world evidence has demonstrated its ability to provide a clinically meaningful response and remission among patients; however, the economic impact of its use may not be favourable from the payer perspective. The objective of this targeted literature review was to understand the economic impact of ustekinumab reference product in the treatment of patients with IBD.

Aims & Methods

A literature search was conducted in MEDLINE for economic publications that evaluate the economic impact of ustekinumab or include ustekinumab within their analyses. Search terms included “budget impact model”, “budget impact analysis”, “cost-utility”, “cost-effect”, “ulcerative colitis”, “Crohn’s disease” and “ustekinumab” from database inception until Feb 8^th, 2024. Only studies published in English were eligible for inclusion.

Results

A total of 30 hits were screened for inclusion, yielding 12 relevant studies that discussed economic implications of ustekinumab. Five articles were conducted from the US payer perspective, two from the Japanese payer perspective, and one each from the Canadian, Swedish, Polish, French, and German perspectives. The economic models included budget impact models (n = 2), cost-effectiveness models (n = 8), and cost per responder/remitter analyses (n = 2). Five studies used a CD patient population, six studies focused on UC, and one study included a mixed population of CD and UC. In CD studies, two found ustekinumab was cost-effective: these studies were conducted from the perspective of Polish and Swedish payers in CD patients who failed anti-TNF therapy. Both studies used a Markov based model to assess cost-effectiveness of treatments. In the remaining CD studies, ustekinumab was associated with the highest cost per responder/remitter (Japanese payer perspective) and was dominated by other treatments in cost-effectiveness analyses (US payer perspective). The studies conducted in the UC patient population also found that, although clinically effective, ustekinumab was dominated (based on the incremental cost effectiveness ratio [ICER]) by other biologics included in the analyses (eg, vedolizumab and infliximab). Similar to the CD patient population, the cost per responder/remitter was highest for ustekinumab compared to five other therapies including tofacitinib and golimumab (US payer perspective). However, in two UC studies, ustekinumab was observed to be more effective than the most cost-effective treatment option (from the Japanese and US payer perspectives), highlighting that its price negatively affected its ICER. Moreover, cost-effectiveness analyses conducted by the German and Canadian perspectives, demonstrated that ustekinumab was not a cost-effective therapy at the current willingness to pay threshold (0% probability). Note, that no studies tested the possible cost-effectiveness of an ustekinumab biosimilar which would positively influence the cost associated with ustekinumab treatment.

Conclusion

This literature review demonstrated that, despite its high efficacy, ustekinumab is among the highest costing biologics available for the treatment of IBD with low probabilities of cost-effectiveness across several studies. As the economic burden for IBD is increasing globally, cost-saving therapeutic options such as biosimilars may help to provide savings that can be redistributed in a healthcare system or provide funds to expand patient access.

Disclosure

Kunal Shastri is an employee of Fresenius Kabi a manufacturer of biosimilars. Kerise Clarke, Margaret Ainslie-Garcia, Nicole Ferko are employees of EVERSANA a company who receives consulting fees from Fresenius Kabi.

Introduction

GLIMMER (NCT02966834) was a Phase 2b study of the ileal bile acid transport (IBAT) inhibitor, linerixibat, for treatment of cholestatic pruritus in primary biliary cholangitis (PBC). The study included 147 patients: the largest trial in this population to date. GLIMMER had few restrictions on concomitant medications with the exceptions of other IBAT inhibitors, bile acid sequestrants and obeticholic acid; stable doses of other treatments were permitted.

Aims & Methods

In this analysis we explore the pruritus treatment history of patients entering GLIMMER. Investigators recorded details of prior and concomitant use of itch medications on the electronic case report form. For categorisation of prior and/or concomitant itch medication: prior only included patients who had tried and stopped at ≥1 pruritus medication before first study treatment and were not using anything else during treatment with linerixibat/placebo; concomitant only included patients who had used ≥1 pruritus medication in the past, which they continued to use during treatment; prior and concomitant included patients who had tried and stopped ≥1 pruritus medication prior to the study and, continued to use ≥1 pruritus medication during treatment with linerixibat/placebo. This post hoc analysis included all treatments prescribed for itch; guideline treatments were defined as bile acid sequestrants, naloxone, naltrexone, nalmefene, nalfurafine, sertraline, rifampicin or gabapentin. Pruritus severity was defined using worst itch numeric rating scale (NRS).

Results

At baseline, 24% of patients had mild (NRS <4), 52% moderate (NRS ≥4–<7) and 25% severe (NRS ≥7–10) pruritus. Mean age at baseline was 55.8 years but varied by itch severity, with mild patients being older (60.1 years) than those with moderate and severe pruritus (56.8 and 49.6 years, respectively). Median duration of pruritus at baseline was 6.3 years and those with mild pruritus tended to have a longer history than those with moderate or severe itch. Overall, a large proportion of patients were never previously treated: 37% (n = 55) had no prior/concomitant itch medications. Similar proportions of patients, 24% (n = 36) and 26% (n = 38), had received only prior itch medications or received prior and concomitant treatment for pruritus, respectively; 12% (n = 18) of patients were using only concomitant itch medications. Only 25% of patients were treated with cholestyramine, despite it being the guideline-recommended first-line therapy. Treatment history differed by baseline itch severity: 43% of mild patients had no prior or concomitant treatment versus 28% of severe patients. However, differences were less marked for concomitant pruritus therapy use: 43%, 36% and 39% of mild, moderate and severe patients, respectively, continued concomitant itch medicines in GLIMMER. The majority of concomitant itch treatments were non-guideline recommended, with only 39% receiving guideline treatments.

Conclusion

Consistent with the literature, increased itch severity is associated with younger age. Many patients do not receive treatment despite lengthy history of pruritus, while prior use of cholestyramine is limited despite its position in treatment guidelines.
Funding: GSK (201000).
Encore statement: This abstract was originally presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting on November 7, 2022, this encore is presented on behalf of the original authors with their permission.

Disclosure

HTS, AC, MMM, AJW and AR are employees of, and hold shares in GSK. SD is an employee of GSK.