Introduction

Crohn’s disease (CD) can lead to inflammation of the intestinal tract and may be complicated by strictures¹. Patients want diet-based approaches to therapy but relatively few prospective diet studies have been conducted with high rates of adherence.

Aims & Methods

We conducted a patient preference study NCT04213729 to test a high fiber(17gm/1000 calories for fiber), low fat(20-25% calories from fat) diet in CD patients. In the current study, we asked whether patients changed their symptoms following the catered diet intervention and whether the CD-related phenotype impacted the response to diet. Patients chose to receive diet counseling alone (group 1), catered food for 8 weeks (group 2), or catered food for a patient and a household member as well as participate in Dyadic Psychosocial Support (DPS)sessions (group 3).DPS sessions incorporated psychoeducational components that combined didactic and behavioral procedures. High fiber catered foods consisted of soluble and insoluble fibers as well as fermentable fibers such as fructans and galactooligosaccharides, etc. Detailed demographic, clinical, anthropomorphic, quality of life, biochemical and food knowledge data were collected at baseline and week 8. A total of 73 patients and 24 household controls were enrolled.

Results

At baseline,60-80%of CD patients were in remission based on PRO2 score (stool frequency≤ 1.5, abdominal pain ≤1)and Harvey Bradshaw index<5. On average, CD patients consumed a diet with less than 9gm/1000 calories of fiber and >40% fat at baseline. All three CD groups were well-matched at baseline with the household controls consuming also less fiber. Patients receiving the catered food had a high rate of adherence to the diet(80%)at week 8; patients receiving diet counseling alone had 5%adherence to a low-fat diet and 10%adherence to a high-fiber diet at week 8. Serum amyloid A(SSA), CRP, and fecal calprotectin were low at baseline and remained low. Catered meals improved values of fecal calprotectin or SAA in the subset of patients that had elevated levels of these biomarkers. Group 3 received DPS sessions for the CD patient and household control and had significantly improved nutrition literacy (score average:70.6,p=0.000636)while groups 1 and 2 averaged 57 and 57.1, respectively. Food-related quality of life(FRQoL 29)scores were significantly improved for those participants that received diet and DPS. FRQoL average increased from 82.1 to 107(p=0.000541).29% had B2 fibro-stenotic disease and received high-fiber catered food. This subset of patients had a decrease in stool frequency and no increase in abdominal pain symptoms. The mean number of bowel movements and pain scores improved or did not change.

Conclusion

CD patients even those in remission, have very low consumption of fruits and vegetables. We show that even patients with B2 phenotype CD can tolerate 8 weeks of high fiber, low-fat diet without worsening of symptoms. One time diet counseling was not able to change diet behavior. Catering meals offers an effective way to control dietary intake in CD clinical trials. Psychology interventions for the CD patient and household improved food-related quality of life and nutritional literacy.

References

1. Rieder F, Zimmermann EM, Remzi FH, Sandborn WJ. Crohn's disease complicated by strictures: a systematic review. Gut. 2013 Jul;62(7):1072-84. doi: 10.1136/gutjnl-2012-304353. Epub 2013 Apr 26. PMID: 23626373; PMCID: PMC4884453.

Introduction

Inflammatory Bowel Diseases (IBD), including Crohn's Disease (CD) and Ulcerative Colitis (UC), pose significant global health challenges. Nutrient deficiencies and malnutrition are common in both forms of the disease. Dietary supplementation with TGF-β has been suggested to enhance patients’ nutritional status, quality of life, and improvement of the symptoms. However, comprehensive evaluations of its clinical impact are needed.

Aims & Methods

This study aims to assess the efficacy of nutritional supplementation in improving clinical outcomes, nutritional status, quality of life, fatigue, disability, and body image among IBD patients.
Methods: Multicenter longitudinal study, enrolling 42 IBD patients in clinical activity and/or at nutritional risk. Patients received the nutritional supplement enriched with TGF-β and underwent assessments before supplementation (M0), at 30 days (M30), and at 60 days (M60) of supplement use. Clinical parameters, disease activity (Harvey-Bradshaw score for CD and partial Mayo score for UC), nutritional evaluation, body composition, presence of fatigue, anxiety and depression, disability, and body image were evaluated. Statistical analyses included descriptive statistics and ANOVA (p<0.05).

Results

42 patients were included: 30 (71%) with CD and 12 (29%) with UC; 48% women, age of 35.1 ± 15.65 years. Among CD patients, 30% were in remission, 16.67% had mild, 43.33% moderate, and 10% severe activity. According to Montreal classification, 36.67% presented ileocolonic disease, 36.67% fistulizing behavior, 26.67% stenosing behavior, 33.33% perianal disease. For UC patients, 41.67% had mild and 58.33% moderate activity; 41.67% presented pancolitis. All patients presented malnutrition or nutritional risk at enrollment. Significant improvements were observed in HBI score comparing M0 (7.97±5.70) vs M30 (4.61±3.16) vs M60 (3.27±1.75), p=0.0055. There was also an improvement of the number of bowel movements (5.45±4.65 vs 2.90±2.02 vs 2.65±1.55). Nutritional assessment revealed a significant increase in brachial circumference (24.23±3.68 vs 25.37±3.51 vs 26.03±4.10, p=0.0182). Fatigue decreased (40.58±14.07 vs 33.12±15.72 vs 30.38±14.88, p=0.0293), as well as disability (51.14±25.34 vs 36±20.89 vs 30.33±22.64, p=0.0032). It was observed an improvement of IBD score (135.08±38.88 vs 145.20±48.27 vs 152.71±58.96; p=0.3737) and body image (10.78±7.37 vs 9.68±8.42 vs 5.57±6.04; p=0.1395), with no significance.

Conclusion

Nutritional supplementation demonstrated notable improvements in clinical and nutritional parameters, as well as reduction in fatigue and disability, underscoring its potential as an adjunctive therapy for IBD management

Introduction

The Endoscopical Submucosal Dissection (ESD) is an advanced resection technique for removing “en bloc” gastrointestinal (GI) lesions, bigger than 20 mm and with macroscopic features of no deep infiltration (limited to the submucosal). It is a complex procedure and, therefore, with risk of complications (early and/or delayed), first of all bleeding, then perforation.

Aims & Methods

Our aim is to confirm the pivotal role of Over-The-Scope Clip (OTSC) for menagement of perforation occurred during the ESD. Our Centre started the ESD techinque from March 2023 by an expert endoscopist, with a collegue in training, and we have included in a database the information of all procedures carried out from that period to September 2023.

Results

Were included 34 adult patient (M/F: 19/15) with an age mean of 69 years. The mean lesions size was of 31 mm ± 20 for the upper-GI, 25 mm ± 15 for the lower-GI. Histological findings were reported in the tab. 1. All procedures were performed under general anesthetic care. Lesions were succesfully resected “en bloc” in all patients (100%) by ESD procedure using minimal CO2 insufflation. The overall intraprocedure perforation occured in 3 out of 34 (8,8%): 1 out of 18 was located in the upper-GI tract (fundus); 2 out of 16 lesions were located in the lower-GI tract (1 in the ascending colon and 1 in the discending colon, respectively). According to clinical and medical stability of the patients, all the parietal defect were treated successfully, at the end of the complete ESD, by positioning OTSC, allowing a full-thickness closure of the GI tract defect, avoiding emergency surgery. The R0 rate was of 94.1%, with two cases that underwent to surgery beacause of “pT2” at the final histological report.

Conclusion

OTSC is a known safe and efficacy device for closing perforation occured during ESD, in the course of the same endosocpic procedure. More and larger studies are needed to further validate these findings.

Introduction

A high body mass index (BMI) may negatively impact treatment efficacy in patients with ulcerative colitis (UC) treated with advanced therapies, such as biologics,¹ which is relevant due to the prevalence of obesity and UC increasing substantially over the past decades.^2,3 Etrasimod is an oral, once-daily (QD), selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active UC.

Aims & Methods

This post hoc analysis of ELEVATE UC 52 and ELEVATE UC 12 investigated the impact of BMI on the efficacy and safety of etrasimod in patients with UC. ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) were phase 3, randomised, placebo-controlled trials.⁴ ELEVATE UC 52 had a treat-through design consisting of a 12-week (wk) induction and 40-wk maintenance period; ELEVATE UC 12 comprised a 12-wk induction period. Patients who received ≥1 dose of etrasimod 2 mg QD or placebo were stratified by baseline BMI: <25 kg/m², 25–30 kg/m² and >30 kg/m². Efficacy outcomes (aligned to the predefined outcomes for the ELEVATE UC 52 and ELEVATE UC 12 trials) included the primary endpoint (clinical remission) and selected secondary endpoints at Wk 12 (data pooled for both trials) and Wk 52 (ELEVATE UC 52 only). Safety outcomes assessed the proportions of treatment-emergent adverse events (TEAEs).

Results

Of the 787 patients enrolled in the ELEVATE UC clinical programme, 443 (56.3%) had baseline BMI <25 kg/m², 217 (27.6%) had baseline BMI 25–30 kg/m² and 127 (16.1%) had baseline BMI >30 kg/m². In the BMI <25 kg/m² and BMI 25–30 kg/m² subgroups, significantly more patients (p<0.05) receiving etrasimod vs placebo achieved all efficacy endpoints at Wks 12 and 52. In the BMI >30 kg/m² subgroup, significantly more patients receiving etrasimod vs placebo achieved clinical remission at Wk 52 (p<0.0001; Wk 12: p=0.05), endoscopic improvement and clinical response at Wks 12 and 52, and corticosteroid-free clinical remission at Wk 52 (all p<0.05; Table). The proportions of patients with the most common TEAEs were generally consistent between BMI subgroups receiving etrasimod. Incidence of serious AEs was generally similar across BMI subgroups receiving etrasimod (<25 kg/m²: 17/308 [5.5%]; 25–30 kg/m²: 8/137 [5.8%]; >30 kg/m²: 1/82 [1.2%]).

Conclusion

In the ELEVATE UC clinical programme, significant improvements in efficacy were observed for patients receiving etrasimod 2 mg QD vs placebo, regardless of baseline BMI. The safety profile of etrasimod was consistent between BMI subgroups and with the overall ELEVATE UC population.

References

1. Kurnool S et al. Aliment Pharmacol Ther 2018; 47: 1472–1479.
2. Molodecky NA et al. Gastroenterology 2012; 142: 46-54 e42; quiz e30.
3. Ng M et al. Lancet 2014; 384: 766–781.
4. Sandborn WJ et al. J Crohns Colitis 2023; 17: 338–351.

Disclosure

AJY has received consultancy fees from AbbVie, Pfizer Inc, Arena, Takeda and Bristol Myers Squibb; and lecture/speaker fees from Bristol Myers Squibb. MDL is a consultant for AbbVie, Janssen, Pfizer Inc, Takeda, Bristol Myers Squibb, Target PharmaSolutions, Prometheus, Lilly, Salix, Valeant, Genentech, Roche, Calibr and Theravance; and has received research support from Pfizer Inc and Takeda. JT has received advisory board fees from AbbVie, Arena, Bristol Myers Squibb, Galapagos, Janssen and Pfizer Inc; research grants from AbbVie and Janssen; and speaker fees from AbbVie, Galapagos, Janssen and Pfizer Inc. NN is a consultant and advisory board member for AbbVie, Bristol Myers Squibb, Janssen, Lilly and Pfizer Inc; and has received research support from Ferring, Janssen, Pfizer Inc and Seres. RKC has received consultancy and advisory board fees from AbbVie, Adiso, Bristol Myers Squibb, CorEvitas, Fresenius Kabi, Fzata, IBD Education Group, Janssen, Magellan Health, Option Care, Pfizer Inc, Sandoz, Samsung Bioepis, Sebela and Takeda; and research grant/support from Janssen. AMA is an employee and shareholder of Pfizer Inc. DB and WN are employees of Pfizer Inc. CMC and JW are employees and shareholders of Pfizer Inc. GP is an employee of Pfizer Healthcare India Private Ltd. MG is an employee and shareholder of Pfizer AG. RP is a consultant for Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Lilly, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma, Trellus, Viatris, Ventyx and UCB; has received speaker fees for AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Lilly, Merck, Organon, Pfizer, Roche, Sandoz, Shire and Takeda; is an advisory board member for AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Lilly, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda and Ventyx; and has received research support from AbbVie, Janssen, Takeda and Pfizer.

Introduction

Short Bowel Syndrome (SBS) is a rare complex disease causing chronic intestinal failure (CIF) for which Parenteral Support (PS) is the reference treatment. Teduglutide (TED), a GLP-2 analogue, is available and reimbursed in France since 2015 for the treatment of SBS-CIF patients. The cost of this drug is very high and there is few data about the number of potential candidates in real life. The aim of the study was to analyze in a real-life setting the implementation of TED in a cohort of SBS-CIF patients as well as the treatment outcomes.

Aims & Methods

This work was a monocentric retrospective study conducted in an expert center of Home PS. We enrolled all patients with SBS-CIF followed in the center between 2015 and 2020. Two sub-populations were defined for this study: the prevalent population, composed of the patients who were already followed in the center before 2015, and the incident population, composed of the new patients who initiated follow-up in the center between 2015 and 2020. Treated and non-treated patients were compared using Wilcoxon-mann-withney or pearson chi2 tests. TED retention rate was calculated using Kaplan-Meier survival estimate.

Results

331 SBS-CIF patients were included in the study (156 prevalent and 175 incident patients). In total, 56 patients initiated a treatment with TED (16.9% of the cohort). 27.9% of prevalent patients initiated treatment, with an annual average rate of 4.3%, against 8.0% of incident patients, with an annual average rate of 2.5%. Treatment with TED allowed a median decrease of 60% (IQR 40-100) of PS volume in our cohort. The reduction of PS was significantly higher in the incident population than in the prevalent population (p=0.02). The long-term retention rate of treatment was 82% after 2 years, 67% after 3 years and 64% after 5 years. Among the non-treated patients, 50 patients (18.2%) were declared non suitable because of non-medical reasons (doubt about compliance, patient refusal, cognitive disorders).

Conclusion

In the prevalent population of SBS patients, more than a quarter of patients were treated with TED, against 8% of incident population. The treatment retention rate is higher than 80% after two years, which can be explained by the careful selection of patients that is important to examine. Furthermore, this real-life study confirms the efficacy of TED in the long term and reports a better response to TED in the incident population, suggesting a benefit of early treatment compared to late treatment.

Disclosure

Research support from Takeda