Introduction

The evidence guiding management of patients with inflammatory bowel disease (IBD) and permanent ileostomy (PI) is limited. We aimed to summarize the evidence for interventional studies related to adjunctive ostomy care including management of high stoma output, skin care, stoma appliances, adhesives, behavioural interventions, mental health, diet, nutrition and disease recurrence.

Aims & Methods

MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to January 5, 2024. Eligible studies were randomized controlled trials (RCTs), non-randomized controlled studies, or comparative cohort studies in English. Studies predominantly recruiting participants with ulcerative colitis (UC) and/or Crohn’s disease (CD) with PI were considered. Studies assessing temporary ileostomy, and ostomies other than PI such as colostomy, urostomy, and jejunostomy were excluded.

Results

A total of 3217 records were identified and independently screened of which six studies were eligible (Table 1). Five studies were published more than 20 years ago (1976-2003) with a small sample size (ranged from 8 to 40). Five studies were double blind RCTs with four studies incorporating a cross over design, and one was non-blinded RCT with a cross over design. Two studies exclusively included patients with UC, one study included CD and the remaining three studies included both UC and CD. No studies included patients with active CD. Four studies assessed pharmacological interventions (loperamide, 5-aminosalysilate [5-ASA], azodisal sodium, and oral budesonide), one assessed oral supplement with different osmolarities and one assessed dietary intervention (unrefined vs. refined carboyhdyrate). Decrease in ileostomy output was primary outcome of interest in four studies (Loperamide, budesonide and azodisal sodium). Outcomes of the remaining two studies include changes in microbial composition and bile acid excretion. Loperamide and budesonide were associated with decreased stoma output. In a study assessing dietary intervention, patients receiving diet rich in unrefined carbohydrates had a ten-fold increase in bacterial load in stoma output compared to patients on a diet rich in refined carbohydrates. One study reported no difference in stoma output between iso- and hyper-osmolar supplements but iso-osmolar supplements were associated with increased natriuresis. The remaining studies were designed to explore the effect of 5-ASAs on ileostomy output in patients with UC and PI.

Conclusion

This study highlights that the evidence base to inform care for patients with IBD and PI is almost non-existent. There is an urgent need for focused research in this area to inform evidence-based treatment decisions. The items identified in this review as well as knowledge gaps will inform consensus steps for development of future care pathways and expert guidelines.

Table 1. Characteristics of interventional studies conducted in patients of inflammatory bowel disease and permanent ileostomy

Disclosure

SKV none
VS has none to disclose.
YY has none to disclose
NN has been a speaker or advisor for Janssen, Abbvie, Takeda, Pfizer, Merck, Sandoz, Fresenius Kabi, Innomar, Iterative Scopes, Bristol Myers Squibb, Viatris and Ferring
SS has received consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenixa, UCB Inc, and Vifor; and lecture fees from AbbVie, Amgen, Ferring Pharmaceuticals Inc, Gilead, Janssen, Mylan, Pfizer, and Takeda.
CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pendopharm, Pfizer, Roche, Sanofi; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Takeda, Pendopharm, and Pfizer; royalties from Springer Publishing; research support from Ferring, Takeda, Pfizer.
FR is consultant to Adnovate, Agomab, Allergan, AbbVie, Arena, Boehringer-Ingelheim, Celgene/BMS, CDISC, Celsius, Cowen, Ferring, Galapagos, Galmed, Genentech, Gilead, Gossamer, Guidepoint, Helmsley, Horizon Therapeutics, Image Analysis Limited, Index Pharma, Jannsen, Koutif, Mestag, Metacrine, Mopac, Morphic, Organovo, Origo, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX,Roche, Samsung, Surmodics, Surrozen, Takeda, Techlab, Theravance, Thetis, UCB, Ysios, 89Bio.
VJ has received consultancy/advisory board fees from AbbVie, Alimentiv Inc., Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert, Ventyx, and Vividion; and speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, and Fresenius Kabi.

Introduction

Eosinophilic esophagitis (EoE) is an immunoallergic disease of increasing prevalence whose clinical manifestations are due to dysmotility resulting from eosinophil-mediated inflammation. The goal of treatment is the clinical, endoscopic and histological response, with discordant data on predictive criteria.

Historically, histological response has been assessed with the intraepithelial eosinophil count until the validation of the Histological Score System (HSS), which includes microabscesses and eosinophilic degranulation, lamina propria fibrosis, intraepithelial lymphocytosis and spongiosis.

Aims & Methods

Our aim is to identify histological features in baseline esophageal biopsies at diagnosis that are predictive of response to proton pump inhibitors (PPI), first line treatment.

A retrospective cohort study, approved by the Ethics Committee of the Hospital Clínico San Carlos, was designed that included incident patients with diagnostic criteria for EoE evaluated between January and December 2022. They underwent a baseline gastroscopy and another after a cycle of PPIs at high doses. After 8-12 weeks induction, two cohorts were established: responders to PPI (PPI-REE) and non-responders (non PPI-RRE). Clinical and endoscopic data were collected from reports, and biopsies were reviewed by expert pathologists after anonymisation of the patient cohort.

Results were analysed using IBM SPSS Statistics v.26, with χ2 or Fisher's exact test for qualitative variables and Student's t-test or non-parametric Mann-Whitney U test for quantitative variables. A binary logistic regression model was used to analyse the association between cohorts and each individual variable, with a significant p-value of 0.005 accepted.

Results

99 patients with EoE were included, 32 in the non-PPI-REE cohort (32.3%) and 67 in the PPI-REE cohort (67.7%), with no differences in baseline characteristics or endoscopic variables. Histological analysis (Table 1) shows that spongiosis, regardless of location, eosinophilic degranulation in the proximal esophagus and fibrosis of the lamina propria in the distal esophagus are predictive factors for non-response to PPI. However, in multivariate analysis, only the presence of spongiosis, regardless of location, was significant (p 0.021 proximal [95% CI 0.030-0.756] and 0.016 distal [95% CI 0.008-0.611]).

Conclusion

EoE is a growing entity. Being able to predict the response to PPIs at diagnosis would allow clinical improvement and early reduction of inflammation, reducing progression to the fibrostenotic phenotype.

According to our results, we consider it important to universalise the HSS, highlighting the importance of identifying spongiosis, easily identifiable histological changes with low interobserver variability and without additional cost, which could predict the absence of response to PPIs, with patients able to benefit from swallowed corticosteroids or exclusion diets from diagnosis. However, studies with greater power should confirm these data.

Introduction

Iron deficiency (ID) and iron deficiency anaemia (IDA) are common complications of inflammatory bowel diseases (IBD). Ferric maltol is an oral iron therapy which increased haemoglobin within 12 weeks and sustainably improved the quality of life in patients with IBD and IDA. [1,2] While IDA is also frequently associated with pregnancy [3], there is no available data on the efficacy and safety of ferric maltol in pregnancy or in pregnant women with ID/IDA.

Aims & Methods

This study documented the first known clinical experience of ferric maltol in pregnant women with IBD and either ID or IDA. Retrospective clinical data from January 2017 to February 2023 in the MVZ Immunology database included pregnant patients with a confirmed diagnosis of IBD and treatment with ferric maltol during their pregnancy. The following patient data were collected: haematological parameters [haemoglobin (Hb), transferrin saturation level (TSAT), soluble transferrin receptor (stfR), ferritin], biomarkers for intestinal inflammation (calprotectin) and safety data. Descriptive results are reported here.

Results

A total of 27 female IBD patients with ID/IDA were included in this analysis, 11 with ulcerative colitis and 16 with Crohn's disease. The mean age was 35.9 years. A total of 29 pregnancies were treated with ferric maltol therapy (two patients had two pregnancies during this period). Prescriptions started after a mean of month 5 of pregnancy. In the course of most pregnancies, dosing was one capsule daily, as patients tended to have mild anemia. The number of prescribed boxes (56 capsules of ferric maltol: one capsule twice a day) per pregnancy was 1 in 82.8% [24/29], 2 in 13.8% [4/29], and 3 in 3.4% [1/29]. Nine cases with Hb < 11g/dl did take two capsules per day. After FM therapy, mean Hb levels increased from 11.3 to 12.36 g/dl (4-7 months), mean stfR levels increased from 1.2 to 1.5 mg/l, and mean ferritin levels increased from 27.2 to 30.0 ng/l, while mean TSAT decreased slightly from 17% to 15.4% (Table). Two patients developed side effects: One had new onset of abdominal pain shortly after starting, one had abdominal pain and increased meteorism. Both patients discontinued ferric maltol treatment and complaints then stopped. At the time of the current analysis, all 27 completed pregnancies proceeded without complications and ended with healthy neonatal infants without abnormalities. Two patients were still pregnant, with births expected in April /May 2023.

Conclusion

These first clinical data on the use of ferric maltol in pregnancy suggest that ferric maltol appears to have a favourable safety profile with few side effects for pregnant patients with IBD and ID/IDA.

References

1. Gasche C, et al. Inflamm Bowel Dis. 2015, 21(3):579-88
2. J.P. Gisbert1, et al. UEG Journal 2022, Vol 10 (S8), MP323, p359
3. Lopez A, et al. Lancet. 2016, 387(10021):907-16

Disclosure

Stefanie Howaldt has served as a speaker or has received research or education funding or advisory fees from MSD, AbbVie, Biogen, Celltrion, Hospira, Takeda, Pfizer, Pharmacosmos, Janssen, R-Biopharm, Norgine, Sandoz, and Shield Therapeutics. Angela Schüller has no conflicts of interest.