Introduction

Etrasimod is an investigational, oral, once-daily, selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). In ELEVATE UC 52 (NCT03945188), etrasimod was superior to placebo (PBO) in achieving Week (Wk) 52 corticosteroid (CS)-free clinical remission (CR).¹

Aims & Methods

This post hoc analysis reports CS-free efficacy and safety in patients (pts) on baseline (BL) CS. Pts were randomised 2:1 to once-daily etrasimod 2 mg or PBO using a treat-through design (12-wk induction and 40-wk maintenance period). At entry, pts could receive concomitant CS (prednisone [≤ 20 mg/day], budesonide [≤ 9 mg/day] or equivalent) if on a stable dose ≥ 4 wks immediately before screening endoscopy; from Wk 12, CS tapering was recommended. CS-free was defined as withdrawal of CS ≥ 12 wks prior to assessment timepoint. CS-free outcomes assessed were CS-free CR at Wk 52, CS-free endoscopic improvement (EI) at Wk 52, and CR at Wk 12 + CS-free CR at Wk 52. From Wk 12, 4-wk CS‑free symptomatic remission (SR; 4 wk in contrast to ≥ 12-wks CS free) was analysed at each visit. Logistic regressions examined associations with CS-free efficacy at Wk 52. Safety was assessed.

Results

At BL, 32.2% (93/289) and 29.2% (42/144) of etrasimod and PBO pts received CS; of these, significantly more etrasimod vs PBO pts achieved CS-free CR at Wk 52, CS-free EI at Wk 52 and CR at Wk 12 + CS-free CR at Wk 52 (all p<0.05; Table). At Wks 40–52, there were significant differences (16.6–26.6%; p<0.05) in 4-wk CS-free SR between etrasimod and PBO. In this subpopulation, being biologic/Janus kinase inhibitor-naïve was not a significant predictor of 12-wk CS-free CR at Wk 52 (odds ratio [OR]: 3.61; 95% confidence interval [CI] 0.91, 14.39; p=0.07); age, per 10-year increase, was significantly associated (OR: 1.51; 95% CI 1.03, 2.22; p=0.04). Etrasimod vs PBO pts with concomitant CS at BL experienced slightly more adverse events (AEs; not exposure adjusted) (71.0% [66/93] vs 61.9% [26/42]) but fewer serious AEs (6.5% [6/93] vs 14.3% [6/42]), including serious infections (0% [0/93] vs 7.1% [3/42]).

Conclusion

More etrasimod vs PBO pts who received CS at BL met CS‑free efficacy endpoints. Four-wk CS-free SR with etrasimod was superior to PBO from Wk 40. Concomitant CS use at BL had no notable negative effect on the safety of etrasimod, consistent with the overall ELEVATE UC 52 population.¹

References

1. Sandborn W et al. Lancet 2023: Epub ahead of print.

Disclosure

BES: grants/research: Arena, Janssen; speaker: BMS, Janssen, Lilly, Pfizer, Takeda; consultancy/advisory board: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer-Ingelheim, BMS, Celltrion, Fresenius Kabi, Genentech, GSK, Janssen, Lilly, Merck, Pfizer, Prometheus Biosciences, Sun Pharma Global, Takeda Pharmaceuticals International, Teva Branded Pharmaceutical Products R&D; stock: Ventyx Biosciences; non-financial support: Janssen, Lilly, Pfizer, Takeda.
YL: speaker: Pfizer Inc, Takeda, Abbvie, Jannsen; Consultancy, Advisory Committee/Board Member: Pfizer Inc, BMS, Takeda, Abbvie, Amgen BioJamp, Lilly.
DTR: grant support: Takeda, Helmsley Charitable Trust, GastroIntestinal Research Foundation; consultancy fees/is a member of advisory boards: AbbVie, AltruBio, ASLAN Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chronicles, Syneos, ClostraBio, Connect Biopharma, EcoR1, Genentech/Roche, Gilead Sciences, Iterative Health, Janssen Pharmaceuticals, Kaleido Biosciences, Eli Lilly, Pfizer Inc, Prometheus, Reistone, Seres Therapeutics, Takeda, Target RWE, Trellus Health; is on the Board of Trustees for Crohn’s & Colitis Foundation and Cornerstones Health, Inc; holds stock options in Alike Health, AltruBio, Datos Health and Iterative Health.
KBG: research support: Celltrion, Galapagos, Pfizer Inc; speaker honoraria and/or consulting fees: AbbVie, Celltrion, Ferring Pharmaceuticals, Immunic Therapeutics, Janssen, Novartis, Pfizer Inc, Samsung Bioepis, Takeda, Tillotts.
JP: personal: AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celltrion, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, GSK, Immunic, Janssen, Mirum, Morphic, Nestlé, Origo, Pandion, Pfizer Inc, Progenity, Revolo, Takeda, Theravance Biopharma and Wassermann; grant support: AbbVie, Pfizer Inc.
MG: employee & shareholder of Pfizer AG.
WW, KS, JCW, CCS: employees & shareholders of Pfizer Inc.
KW: employee & shareholder of Pfizer Canada Inc.
SS: speaker: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Fresenius, Janssen, MSD, Pfizer Inc, Takeda; consultancy/advisory: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Fresenius, Gilead Sciences, IMAB, Janssen, MSD, Mylan, Pfizer Inc, Protagonist, Provention Bio, Takeda, Theravance.

Introduction

Studies have shown that most foreign body (FB) pass without the need for intervention (1).
European Society of Gastrointestinal Endoscopy (ESGE) recommends urgent endoscopic retrieval of high-risk objects such as sharp, blunt (magnets, button batteries) and long objects,(2) but decision regarding endoscopic retrieval is often taken ‘case by case’ with variation in clinical practice.

Aims & Methods

We set out to evaluate and compare outcomes in cases where FB ingestion was managed conservatively versus cases where an attempt at gastroscopy (OGD) retrieval was undertaken.
This was a retrospective cohort analysis performed in a large tertiary centre reviewing FB ingestion presentations between January 2020 to December 2024. Cases were identified using an electronic coding system and adults (aged 18 and above) were included. Food impaction cases were excluded. Data analysis included demographics, early warning score (EWS) at presentation, prior FB ingestion and intervention episodes. FB type was categorised as blunt, long (5cm or more), sharp and other. Location of FB in the gastro-intestinal tract at presentation was documented where possible. For analysis, groups were categorised to those who had OGD versus those conservatively managed (no OGD).
Outcomes were categorised as eventful (defined as requiring surgical intervention for retrieval or complications such as perforation, obstruction, hemorrhage, foreign body migration through the digestive wall or death) or uneventful, defined as foreign body passing through spontaneously. Length of hospital stay (LOS) was also compared between both groups.
Chi squared, Man Whitney U and Kruskal-Wallis test were used for statistical evaluation. P value of less than 0.05 is considered significant.

Results

A total of 119 presentations were analysed (n=73 Females n=46 Males) with a median age of 38 years. Median EWS at presentation was 1. Location of FB identified at presentation were as follows; oesophagus n=11, stomach n=72, beyond n=27, radiolucent n=9.
Categories of FB, comparison between groups (OGD versus no OGD) and outcome is summarised in table 1.
Overall, 0.08% (n=7 for OGD and n=3 for no OGD respectively) of presentations had an eventful outcome. There is no significant difference observed in the number of eventful outcomes between the OGD and no OGD group (p=0.282). There is no significant difference in LOS (days) between the two groups (OGD group median = 3 days IQR 3 versus no OGD; median = 2 days IQR 4, p 0.198)
Eventful outcome occurred in all categories of FB (blunt n=3, sharp n=3, long n=3, other n=1) and location (oesophagus n=2, stomach n=7, beyond n=1).
There is a trend that those who had intervention previously for FB ingestion will have had more overall presentations (Kruskall-Wallis p=0.044).

Table 1 - Category of foreign body, OGD performed, outcomes and comparison.

Conclusion

Our study observed an overall low eventful outcome following foreign body ingestion presentation. There is no significant difference in outcomes and LOS between patients who had OGD versus those managed conservatively.

References

1. Tambakis G, Schildkraut T, Delaney I, Gilmore R, Loebenstein M, Taylor A, Holt B, Tsoi EH, Cameron G, Demediuk B, Miller A, Connell W, Wright E, Thompson A, Holmes J. Management of foreign body ingestion in adults: Time to STOP and rethink endoscopy. Endosc Int Open. 2023 Dec 12;11(12):E1161-E1167. doi: 10.1055/a-2201-6928. PMID: 38094028; PMCID: PMC10715904.
2. Removal of foreign bodies in the upper gastrointestinal tract in adults: European Society of Gastrointestinal Endoscopy (ESGE) clinical guidelines. http://dx.doi.org/ 10.1055/s-0042-100456 Published online: 0.0.2016 Endoscopy 2016; 48: 1–8 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X

Introduction

Approximately 15-19% of patients suffering from irritable bowel syndrome (IBS) have an eating disorder (ED) based on a screening score or dietary assessment (1). Avoidant/restrictive food intake disorder (ARFID), a long-recognised eating disorder in children, is now recognised in adults. In a Swedish study, 13.2% of patients suffering from IBS reported severe dietary avoidance or restriction, suggestive of ARFID (2). A screening questionnaire for this disorder has recently been validated in French (NIAS-Fr, for Nine Item ARFID Screen in French) (3).

Aims & Methods

This study aims to assess the prevalence of ARFID in IBS in France, by comparing the NIAS-Fr questionnaire and the assessment by a specialised dietitian, and to look for links between its presence and the clinical phenotype of patients. This study was conducted between February and September 2024 in consecutive patients suffering from IBS and evaluated in a multidisciplinary day hospital structure. Clinical characteristics (age, gender, BMI, IBS subtype and its severity [IBS-SSS], presence of functional dyspepsia, diet and disease duration) and presence of ARFID (clinically or one abnormal NIAS-Fr subscale) were collected. A dietitian assessed the presence of “clinical ARFID”. The NIAS subscales allow for the diagnosis of patients as “picky eaters” (score ≥10), with “poor appetite” (score ≥9) and/or with a “fear of eating” (score ≥10). Patients with a history of ED diagnosed by a psychiatrist and/or an abnormal ED screening score (SCOFF ≥ 3 and/or global EDE-Q8 ≥ 4.0) were excluded from the analysis.

Results

Of the 95 patients with IBS according to Rome IV, 55 (57.9%) had at least one positive NIAS-Fr subscale, with 10 (10.5%) having an abnormal “picky eater” subscale, 16 (16.8%) an abnormal “poor appetite” subscale, and 49 (51.6%) an abnormal “fear of eating” subscale. Of these 95 patients, 15 were excluded from the analysis because of a history of eating disorders or an abnormal screening score. We therefore included 80 patients for analysis (77.5% women; mean age 48.5 ± 16.8 years, BMI 22.6 ± 4.6 kg/m²; 40.0% IBS-D, 38.8% IBS-C, and 20.0% IBS-M; 51.3% had associated dyspepsia; 62.5% were on a special diet at the time of assessment). The mean IBS-SSS score was 319.5 ± 88.2 points (severe forms in 61.2%). Among these 80 patients, 43 (53.8%) had at least one positive NIAS-Fr subscale, including 10.0% of "picky eaters," 16.3% of "poor appetite," and 48.8% of "fear of eating." Patients with at least one positive NIAS-Fr subscale had more frequent functional dyspepsia than those with a negative NIAS (65.1 vs. 35.1%, p = 0.013), but there were no differences in the other parameters assessed. According to the dietitian's assessment, 19 (23.8%) patients in our cohort had clinical ARFID, i.e., 44.2% of those with at least one positive NIAS-Fr subscale. In an IBS population, the specificity of the NIAS-Fr questionnaire for diagnosing clinical ARFID was 55.8% (95% CI: 41.1-69.6). None of the assessed parameters distinguished patients with and without clinical ARFID (p > 0.05).

Conclusion

ARFID symptoms are found in more than half of IBS patients treated in a tertiary care centre based on an abnormal NIAS-Fr screening questionnaire, after excluding other eating disorders. These patients frequently have associated functional dyspepsia and a normal BMI. Based on a dietary assessment, clinical ARFID is found in approximately one-quarter of IBS patients. The specificity of the NIAS-Fr in IBS is too low to allow a diagnosis of ARFID in this population.

References

(1) Wuestenberghs et coll. Intérêt du dépistage des troubles du comportement alimentaire au cours du syndrome de l’intestin irritable. JFHOD 2024 (number 000694)
(2) Melchior et coll. Food Avoidance and Restriction in Irritable Bowel Syndrome: Relevance for Symptoms, Quality of Life and Nutrient Intake. Clin Gastroenterol Hepatol. 2022;20(6):1290-1298.e4.
(3) Van Ouytsel et coll. Translation of the nine item avoidant/restrictive food intake disorder screen (NIAS) questionnaire in French (NIAS-Fr). Neurogastroenterology & Motility 2024 ; 36 (4) : e14757.

Disclosure

Nothing to disclose.

Introduction

The low FODMAP diet (LFD) is an efficacious dietary intervention for reducing symptoms in patients with irritable bowel syndrome (IBS). Although effective, the LFD is complex, requires guidance from a trained dietitian and may be associated with decreased caloric intake and weight loss. A less strict diet intervention, by a self-guided smartphone application (FODMAP-light DOMINO app), showed superiority compared to standard medical therapy in primary care IBS patients¹. The efficacy of the FODMAP-light app in tertiary care patients has not been evaluated.

Aims & Methods

We aim to evaluate the efficacy of the FODMAP-light app for managing IBS in tertiary care. To this end, we assessed its impact on IBS symptoms, nutritional intake and psychosocial comorbidities.
After a two-week baseline period, IBS patients were instructed to follow the FODMAP-light diet app during eight weeks. A symptom diary, including the Bristol stool scale (BSS), was filled out daily. IBS symptoms were scored on a 0-100mm Likert scale. Stool consistency was reported as days per BSS types (1-7) over two weeks. Seven-day food diaries were collected during baseline and diet period. Questionnaires to assess IBS symptom severity (IBS-SSS) and psychosocial comorbidities (PHQ and GAD-7) were filled out at baseline and after diet. Data are reported as mean±SD or median (IQR).

Results

Among 53 patients with IBS (81% female, age 32 (28-42) years, BMI 23 (20-29) kg/m²), the diet significantly reduced IBS-SSS (287±72 vs. 172±91, p < 0.0001) with an 81% responder rate (≥50 points improvement). Compared to baseline, duration (41 (30-54) vs. 17 (7-31)) and severity (39 (26-52) vs. 14 (6-33)) of abdominal pain, bloating (44 (27-55) vs. 19 (8-31)), flatulence (46 (29-57) vs. 18 (9-30)), and impact on daily life (38 (24-51) vs. (16 (6-37)), significantly improved during the diet (all p < 0.0001). Stool frequency remained unchanged, but there was a significant shift from loose (BSS type 6 and 7) to normal stools (BSS type 2,3 and 4) (p < 0.0001), and episodes of urgency significantly decreased (p < 0.01). Nutritional analysis, shown in table 1, revealed a decreased caloric intake (∆-186.1 kcal/d, p < 0.0001), but no weight loss. Intake of FODMAPs decreased significantly, except for lactose and mannitol. Psychosocial outcomes improved significantly, with reduction in somatization (11 (8–14) vs. 8 (6-12), p < 0.0001), depression (5 (3–11) vs. 4 (2–6), p < 0.0001), and anxiety (6 (3–9) vs. 4 (1–6), p < 0.001).

Conclusion

The DOMINO FODMAP-light app is an effective treatment option for improving gastrointestinal as well as psychosocial factors in tertiary care IBS, providing a promising alternative to more restrictive dietary approaches.

References

1 Carbone F and Van den Houte K et al. Gut. 2022

Introduction

There is currently no recommendation regarding preferred drugs for eosinophilic esophagitis (EoE) because their relative efficacy is unclear.

Aims & Methods

We conducted an up-to-date network meta-analysis to compare proton pump inhibitors, off-label and EoE-specific topical steroids, and biologics in EoE. We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to February 2023. We included randomized controlled trials (RCTs) comparing efficacy of all drugs versus each other, or placebo, in adults and adolescents with EoE. Results were reported as pooled relative risks with 95% confidence intervals to summarize effect of each comparison tested, with drugs ranked according to P-score.

Results

We identified 13 RCTscontaining 1327 subjects with EoE. For histological remission defined as ≤15 eosinophils/high-power field (eosinophils/HPF), budesonide orally disintegrating tablet 1mg b.i.d., fluticasone orally disintegrating tablet 1.5mg b.i.d. and 3mg b.i.d., and dupilumab 300mg weekly ranked first, second, third, and fourth, respectively. Results were similar when histological remission was defined as ≤6 eosinophils/HPF. EoE-specific formulations were generally superior to adapted asthma medications in achieving histological remission. For failure to achieve symptom improvement, only budesonide orally disintegrating tablet 1mg b.i.d. and budesonide oral suspension 2mg b.i.d. were significantly more efficacious than placebo. For failure to achieve endoscopic improvement based on the EoE endoscopic reference score, only budesonide orally disintegrating tablet 1mg b.i.d. and budesonide oral suspension 1mg b.i.d. or 2mg b.i.d. were significantly more efficacious than placebo.

Conclusion

Most drugs are effective for achieving histological remission in active EoE, but few are superior to placebo in terms of symptomatic or endoscopic improvement.