Introduction

Mesalazine suppositories are recommended in guidelines for the induction and maintenance of remission in patients with ulcerative proctitis (UP). Nevertheless, nonadherence can be frequent and the recommended dose of mesalazine suppositories in maintenance treatment remains unknown.

Aims & Methods

The aim of this study was to determine the frequency of non-adherence to mesalazine suppositories, evaluate potential factors for nonadherence and the impact on quality of life and number of relapses in patients with UP.
Methods: A multicenter, prospective observational study was designed in patients ≥18 years old with UP under maintenance treatment with mesalazine suppositories (Claversal© 500 mg, Pentasa© 1g or Salofalk©1g). We evaluated adherence, socio-demographic data and complications associated with poor adherence at 6 and 12 months. Adherence was assessed by tracking pharmacy refills (medication possession ratio, MPR). We defined good adherence as MPR ≥80% over 12 months. Health-Related Quality of Life (HRQoL) was evaluated using the disease-specific shortened Spanish version of the IBDQ (SIBDQ-9). Relapse was defined as partial Mayo ≥2; biological remission as a partial Mayo score <2 and fecal calprotectin ≤150. Multivariate analysis allowed us to determine the risk factors for non-adherence to mesalazine suppositories.

Results

A total of 188 patients with mean age 51 were consecutively included across 14 Spanish hospitals (Table 1). Of these, mean MPR was 76% and 56% presented MPR ≥80%. Mean age was higher among patients with MPR ≥80% (p=0.045). A total of 125 (71,4%) patients were in biological remission, 31 patients (16%) had a relapse and 3 (1.6%) patients were hospitalized during the follow-up. The use of corticosteroids during the follow-up (OR=4.25, p=0.041) were associated with better adherence. There were no differences between the different brands and doses of suppositories analyzed. Low adherence was not related with increased number of flares (p=0.927), hospitalizations (p=0.225) or decreased quality of life (p = 0.353) over the 12 months of follow-up.

Conclusion

Almost half of patients with UP on maintenance treatment with mesalazine suppositories have low adherence. The use of oral corticosteroids during the follow-up may increase adherence, but poor adherence to mesalazine suppositories was not related with risk of relapse, hospitalizations or worst quality of life.

Disclosure

Manuel Barreiro de Acosta: speaker, consultant and advisory member for or have received research funding from AbbVie, Janssen, Takeda, Pfizer, Lilly, Alphasigma, Sandoz and Oncostellae

Introduction

Hyperbaric oxygen therapy (HBOT) is a treatment that delivers 100% oxygen in a pressurized chamber. HBOT enhances tissue oxygenation and neovascularization and proved clinical efficacy in chronic wounds, post-radiation proctitis and enteritis, perianal fistulizing Crohn’s disease, and acute severe ulcerative colitis. Refractory ulcerative colitis (UC) remains a major therapeutic challenge.

Aims & Methods

We evaluated the tolerability, preliminary efficacy, and mechanistic effects including perfusion kinetics measured with intestinal ultrasound (IUS) of 10 and 20 sessions of HBOT in patients with UC. PARADOX was an investigator-initiated, prospective, open label, uncontrolled, dose-finding pilot trial (phase 2a) in biologic-experienced patients with moderate-to-severe, highly refractory UC with a follow-up of 26 weeks (Mayo score >5, MES ≥2, failed ≥2 classes advanced therapies). Patients (n=16; 8 per arm) continued optimized, stable dose background therapy and received 10 or 20 sessions HBOT (2.4 ATA, 120 minutes per day with two 5-minute air breaks). The primary efficacy outcome was predefined composite clinical and endoscopic response (3-point and 30% decrease in Mayo score, RB = 0 and 1-point decrease in MES) at week (W) 12. Other outcomes included tolerability; clinical, symptomatic, endoscopic, and biochemical response, and transmural response assessed by IUS including contrast-enhanced ultrasound (CEUS) to evaluate bowel wall thickness (BWT), vascularity and perfusion kinetics. Endoscopy and IUS were centrally read and adjudicated.

Results

Baseline characteristics were comparable in both cohorts with median age: 48 vs 64 years; disease duration: 12 vs 9 years; ≥4 prior advanced therapies: 3/8 in both; Mayo score: 10.5 vs 9.
At W12, the predefined composite clinical and endoscopic response rate was met in 2/8 patients with 10 sessions and 4/8 patients with 20 sessions. Clinical, endoscopic, symptomatic, biochemical, and IUS parameters all improved over time in both HBOT cohorts with a trend towards larger improvement after 20 compared to 10 sessions (See Table).
At W12, clinical responders demonstrated a significant increase in peak enhancement on CEUS compared to baseline (12.1 dB, 95% CI: 0.8 to 34.3), while non-responders showed a numerical decrease (–5.4 dB, 95% CI: –20.9 to 4.0). This divergent trajectory was consistent across perfusion parameters related to both wash-in and wash-out (e.g., time to peak, wash-in and wash-out rate, area under the curve), suggesting a treatment-related vascular response. In contrast, early gains in non-responders had waned by W12. This effect was numerically larger after 20 sessions, supporting a potential dose–response effect.
HBOT was well tolerated with no dose-limiting toxicities.

Conclusion

HBOT is a feasible adjunctive therapy in treatment-refractory moderate-severe UC. CEUS showed improved intestinal perfusion in HBOT responders, which offers promising non-invasive tools for response assessment. These findings provide a rationale for a randomized dose-optimized phase 2 trial with potentially longer duration of treatment.

Introduction

Few studies have evaluated the efficacy of butyric acid in treating children with inflammatory bowel disease (IBD).

Aims & Methods

In children and adolescents with recently diagnosed IBD, the purpose of this research was to assess the efficacy of oral sodium butyrate as an adjunct to conventional treatment.This trial was unicentric, prospective, randomised, and placebo controlled. 150 mg sodium butyrate single dose (group A) or a placebo (group B) were randomly assigned to patients with ulcerative colitis or Crohn's disease aged 7–18 years who were receiving conventional medication based on the severity of their conditions. Disease activity, C-reactive protein (CRP), and faecal calprotectin concentration differences between the two study groups at 12 weeks of the trial were the main outcomes.

Results

With 44 patients in group A and 44 in group B, 88 individuals with initially active illness finished the research. Most patients experienced remission by week 12 of the study (36 patients in Group A with sodium butyrate-82%, and 11 patients in Group B with placebo-48%). Between the two groups, a significant difference in disease activity was seen (p = 0.001), with a signifigant higher percent of cases in remission among those from lot A that received sodium butirate compared to placebo. The sodium butyrate group appeared to have less systemic inflammation than the other group, as evidenced by the significantly lower CRP levels in Group A (18.14 ± 11.19 mg/L) compared to Group B (57.00 ± 33.28 mg/L) at 12 weeks (T2) (P < 0.001). No negative effects were recorded by any of the patients. Fecal calprotectin in Group A dropped much more after 12 weeks (T2) (P < 0.001), suggesting that the sodium butyrate group was better able to regulate intestinal inflammation.

Conclusion

In newly diagnosed children and adolescents with IBD, a 12-week sodium butyrate supplementation did demonstrate effectiveness as an additional treatment and decreased the rate of relapsing cases.

Disclosure

Nothing to disclose

Introduction

Glucagon-like peptide-2 (GLP-2) analogs stimulate adaptation of the remaining gut of patients with short bowel syndrome and intestinal failure (SBS-IF), resulting in increased intestinal absorption. Overall, preclinical data suggest intestinal permeability may be compromised in patients with SBS, which may contribute to fluid losses. However, it remains unclear whether this can be improved by GLP-2 analog treatment.

Aims & Methods

STARS Nutrition was a 52-week multicenter, open-label, phase 2 study in adult patients with SBS-IF and a colon-in-continuity (CiC) (Leuven n=7, Paris n=2) receiving weekly subcutaneous injections with the novel, long-acting GLP-2 analog apraglutide. Duodenal and sigmoid colon biopsies were collected at screening, 24 weeks, and 48 weeks of treatment. Ussing chamber experiments were performed (Leuven only) to measure the transepithelial electrical resistance (TEER) and passage of a 4 kDA fluorescently-labelled dextran molecule (FITC-D4). In addition, qRT-PCR experiments were performed for genes of tight junction- and intercellular adhesion-related proteins. Data are presented as median (min – max). Nominal p-values are calculated using Wilcoxon matched-pairs signed rank tests (significance ≤0.05).

Results

The baseline colonic TEER of 21.56 (12.50 – 28.33) Ω.cm² significantly increased to 27.22 (22.78 – 32.67) Ω.cm² (p=0.0156) at 48 weeks. In addition, the baseline FITC-D4 flux of 34.75 (19.35 – 59.03) pmol was significantly reduced to 17.42 (10.03 – 45.28) pmol (p=0.0469) at 48 weeks. There were no significant changes in gene expression in the duodenum or sigmoid colon.

Conclusion

Apraglutide in SBS-IF-CiC led to significantly improved colonic permeability, potentially contributing to its pro-adaptive effect.

Disclosure

This research was supported by VectivBio, now part of Ironwood Pharmaceuticals.

Astrid Verbiest, Joran Toth, Pauline Huyghe, Lise De Meyere, Lucas Wauters, Ricard Farré: no disclosures.
Palle Bekker Jeppesen: PBJ has received grants/research support/honoraria or consultation fees from Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast, Ferring, Fresenius Kabi, GLyPharma, Naia Pharma, NPS Pharmaceuticals, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectivBio and Zealand Pharma.
Francisca Joly: FJ has received grants/research support/honoraria or consultation fees from Baxter, Fresenius Kabi, Nestlé Health Sciences, BBraun, Theradial, Mayoli, Biocodex, mobile3e Consulting, Carembouche, NPS Pharmaceuticals, Shire, Takeda, Therachon, VectivBio and Zealand Pharma.
Tim Vanuytsel: TV has served on the speaker bureau for Fresenius Kabi, Remedus, Takeda, and VectivBio. TV has provided clinical advice to Baxter, Shire, Takeda, VectivBio, Zealand Pharma. TV has received research grants from Takeda and VectivBio.