Introduction

Despite the importance of granulocytoapheresis (GCA) in the treatment of inflammatory bowel disease (IBD), its effectiveness in steroid-dependent and steroid-refractory IBD has not been widely evaluated, the approaches are heterogeneous and data on efficacy and safety remain limited in our population.

Aims & Methods

This study aims to assess the effectiveness of GCA for induction of remission and maintenance in patients with steroid-dependent and steroid-refractory IBD in the real-world practice.
Retrospective cohort of patients with steroid-dependent and steroid-refractory colonic IBD, in which GCA was used as induction of remission and maintenance treatment between January-2015 to January-2023. We analyze demographics, disease characteristics, prior exposure including biologic agents. The success of GCA was defined on a decrease of at least 3 points in the True-love score for Ulcerative Colitis (UC) and a decrease of at least 100 points in the CDAI for Crohn Disease (CD).
To analyze predictive factors of treatment success we performed a univariate and multivariable analysis.

Results

49 patients were included. 5 cycles of apheresis were performed in the first 3 weeks as induction and at least 10 cycles of apheresis as maintenance in the next 6 months.
75 % (37 / 49) had UC, 86.4 % (32 / 37) were steroid-refractory while 13.6 % (5 / 37) steroid-dependent, 54 % (20 / 37) male; median age 60 ± 10.5 years with a mean of 10.5 years from diagnosis. 67.7 % (25 / 37) had received at least 1 biological treatment in the past, 43.5 % (17 / 39) ≥ 2 biological. After induction, 75 % (28 / 37) responded to treatment, 62 % (23 / 37) continued with maintenance therapy of which 67 % (15 / 23) responding. Mean PCR and calprotectin were 3,16 mg / dl and 2038 mg / dl before treatment, 1.45 mg / dl and 1025 mg / dl after induction, 1.15 mg / dl and 900 mg / dl after maintenance, respectively.
25 % (12 / 49) had CD, 50 % (6/12) male; median age 62 ± 9.8 years, 75 % (9 / 12) steroid-refractory and 25 % (3 / 12) steroid-dependent, with a mean of 9 years from diagnosis, 67.7 % had received at least one biological treatment in the past. After induction, 58 % (7 / 12) responded, 80 % (10 / 12) continued with maintenance with 50 % (5 / 10) responding. Mean CRP and calprotectin were 3.16 mg / dl and 3645 mg / dl before treatment, 1.7 mg / dl and 2473 mg / dl after induction, 1.14 mg / dl and 623 mg / dl after maintenance.
Factors such as smoking, extent of disease, longer disease course and lack of response to previous treatments, were not significantly related to response in either induction or maintenance.
No patient had major adverse events recorded.

Conclusion

GCA appears to be safe and effective for inducing and maintaining clinical remission in patients with IBD, especially in patients with UC. No significant differences were found in disease extension, duration or lack of response to previous treatments.

Introduction

Ustekinumab (UST) is a monoclonal antibody that inhibits the p40 subunit of IL-12 and IL-23, approved for the treatment of Crohn's Disease (CD) and Ulcerative Colitis (UC). Its administration is intravenous during induction and subcutaneous during maintenance. Several studies have assessed the efficacy of reinduction and intensification of this treatment in patients with loss of response. However, there are few studies evaluating the effectiveness of intravenous UST for maintenance.

Aims & Methods

The aim of the study is to evaluate the efficacy and safety of maintenance with intravenous UST in patients with Inflammatory Bowel Disease (IBD).
Observational, retrospective, and single-center study. All patients receiving maintenance with intravenous UST until June 2023 were reviewed. Clinical response was evaluated with Harvey-Bradshow Index for CD and partial Mayo for UC. Biochemical response was evaluated with calprotectin and C-reactive protein.

Results

A total of 29 patients with IBD (24 CD and 5 UC) were included. The mean follow-up of patients was 449 days (74-948). The cohort's characteristics are summarized in Table 1.
In all cases, intravenous maintenance was performed with UST 130mg/4 weeks. In 4 cases (13.8%), maintenance was initiated directly with intravenous UST. In 9 (31%) patients due to primary failure to UST and in 16 (55.2%) patients due to secondary failure.
The clinical response to intravenous UST maintenance in patients with CD at week 8 and 16 and at one year of follow-up was 87.5% (n=21/24), 83.3% (n=20/24), 73.3% (n=11/15) respectively. For UC, the response was 60% (n=3/5) at week 8 and 16 and at one year. The drug survival was 723 days (± 74) (Figure 1). No predictive variable for treatment response was identified. Two patients (both with CD) experienced recurrent respiratory infections as an adverse effect, without the need to discontinue UST.

Conclusion

Maintenance treatment with intravenous UST can be useful and safe in patients with severe IBD and/or failure of subcutaneous UST maintenance.

Introduction

Biologic therapies are associated with an increased risk for adverse events such as infections and malignancies. This is of particular importance in elderly patients with inflammatory bowel disease (IBD).

Aims & Methods

The aim of this study was to compare the efficacy and safety of different biologic therapies between IBD patients aged over 60 years and younger patients.All adult patients with IBD treated with biologic agents from 2010 to 2022 in the sole tertiary referral center for inflammatory bowel disease in central Greece were screened for eligibility and their electronic medical records were retrospectively reviewed. Data collected included the socio-demographic and clinical characteristics of the study population, endoscopy reports as well as information regarding treatment compliance and drug sustainability. Adverse events (AEs) and serious AEs were also recorded. Patients with incomplete information were excluded from the analysis.

Results

267 IBD patients were screened for eligibility and 187 were included. The majority (65%) of the patients had Crohn's disease. Of all patients, 47.8% received infliximab, 18% adalimumab, 18% vedolizumab, and 16% ustekinumab. The median duration of biologic treatments was 10 years. Parallel steroid therapy was required in 70% at baseline, 35% at 3 months, 18 % at 6 months, and 5% at 12 months from treatment onset. The efficacy of biologic therapies did not differ significantly between patients aged > 60 years and younger patients. Kaplan-Meyer analysis did not show statistical differences or trends in drug sustainability (P > 0.05), time to an adverse event (P >0.05), and infection rates (P >0.05) among the different classes of biologic agents compared. The most common AEs leading to drug discontinuation were loss of response and local injection site reactions. After adjusting for differences in baseline characteristics between the two age groups, no significant differences in drug sustainability and the need for treatment optimization were found between elderly and younger patients (p >0.05).

Conclusion

Available biologic therapies were characterized by comparable efficacy, sustainability, and safety among elder and younger patients, hardening the preferential selection among the available biologic agents for the elderly. More real-world evidence is required to make treatment recommendations.

References

1. de Silva S, Devlin S, Panaccione R. Optimizing the safety of biologic therapy for IBD. Nat Rev Gastroenterol Hepatol. 2010 Feb;7(2):93-101. doi: 10.1038/nrgastro.2009.221. PMID: 20134491.
2. Lasa JS, Olivera PA, Danese S, Peyrin-Biroulet L. Efficacy and safety of biologics and small molecule drugs for patients with moderate-to-severe ulcerative colitis: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2022 Feb;7(2):161-170. doi: 10.1016/S2468-1253(21)00377-0. Epub 2021 Nov 29. PMID: 34856198.

Introduction

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex conditions characterized by significant clinical, immunological, molecular, genetic, and microbiological heterogeneity. Current therapeutic strategies, particularly biologics and Janus kinase (JAK) inhibitors, are effective for inducing clinical remission and controlling inflammation. However, one-third of patients fail to respond to these treatments, highlighting the need for predictive biomarkers to better tailor therapy and improve outcomes.

Aims & Methods

In this study, we conducted a multi-omic approach, integrating transcriptomics, proteomics, metabolomics, and metagenomics to identify biomarkers of treatment response in IBD. A cohort of 57 active CD and 70 active UC patients was analyzed before and after 14 weeks of treatment with anti-TNF, ustekinumab, vedolizumab, or tofacitinib. Response was evaluated using endoscopic criteria, categorizing patients as responders or non-responders. Biological samples [serum, urine, serum extracellular vesicles (EVs), intestinal biopsies, and stool] were analysed using RNA sequencing, liquid chromatography-mass spectrometry, nuclear magnetic resonance, and 16S rRNA gene sequencing to assess molecular and microbial profiles.

Results

Our results identified multiple mRNAs, proteins and metabolites associated with treatment response. Gene expression analysis in intestinal tissue showed significant differences between UC patients responders and non-responders to vedolizumab. Proteomic analysis of serum EVs and intestinal tissue samples revealed differentially expressed proteins between different study groups. Metabolomic analysis identified deregulation of 24 serum lipoproteins from CD responders to ustekinumab compared to non-responders. Pathway analysis highlighted significant enrichment in ketone and butyrate metabolism, mitochondrial electron transport chain activity, carnitine synthesis, and fatty acid oxidation pathways. Metagenomic analysis revealed microbial differences in UC patients responders to anti-TNF therapy compared to non-responders.

Conclusion

This multi-omics analysis uncovers promising biomarkers that could serve as predictive indicators of therapeutic response to biologics and JAK inhibitors. Nevertheless, further studies are crucial to confirm these findings and evaluate their clinical relevance in identifying patients most likely to respond to tailored therapeutic interventions. One of the challenges is integrating results from different omics approaches to create a more holistic understanding of the disease, potentially opening doors for more precise/early detection through multipanel biomarkers.

Introduction

Anti-TNF alfa and Azathioprine (AZA) are treatments of choice in the setting of steroid-dependent Inflammatory Bowel Disease (IBD). Thanks to its low cost (with the advent of biosimilars),manageability and lack of immunogenicity Adalimumab (ADA) is the most used anti-TNF. Comparative data between ADA and AZA are scanty.

Aims & Methods

The aim of this study was to compare ADA and AZA in terms of efficacy, safety and persistence in treatment in patients with steroid dependent IBD naive to biologics and/or immunosuppresive therapy. A retrospective-prospective observational study was conducted on consecutive IBD-patients in follow up in our tertiary referral center, who started ADA or AZA between 01/2016 and 01/2022. A minimum follow up of 12 weeks was required. Drug choice was upon clinical judgement. Primary outcome was clinical remission at week 12, 36, 60 and 84, assessed by HBI for CD and p-Mayo score for UC. Secondary outcomes were probability of persistence in treatment and safety.

Results

100 patients were enrolled (54 CD, 46 UC), The two treatment groups showed similar baseline characteristics regarding age, sex, familial predisposition, smoking, previous surgery, and concomitant therapies. The use of systemic steroids at week 0 was documented in 25/48 (52,1%) of patients who started ADA and in 18/52 (28,9%) patients on AZA (p=0,079). The results on primary outcome are described in the table below. In CD both treatments showed similar effectiveness, while patients affected by UC had a significant higher rate of clinical remission when treated with AZA. Six adverse events were registered in the ADA group, 13 AE occurred in the AZA group (p=0,113). Overall retention rate was 38/48 (79,2%) for ADA and 29/52 (55,7%) for AZA (p=0,013). The cumulative probabilities of persistence in treatment was similar in the two groups (p=0,554), but after 84 week a higher trend to treatment discontinuation was observed with AZA. According to IBD type, treatment persistence with ADA was higher in patients with CD (p=0,007) with a retention rate of 92,9% for ADA versus 42,3% for AZA (P<0,001); while in UC the cumulative probability of persistence in treatment was higher for patients treated with AZA (p=0,016) with a retention rate of 69,2% versus 60% for ADA (p=0,519).

Conclusion

Our results show good effectiveness, in terms of clinical remission, in patients with CD in both treatment groups, although ADA has a significant higher probability of persistence in treatment. In UC, AZA group have significant better effectiveness and higher retention rate compared to ADA, while the cumulative probability of persistence in treatment is not statistically significant. These findings suggest the need of a different therapeutic approach in steroid-dependent CD and UC; in particular AZA should be preferred to ADA in patients with UC. In CD both treatments represent a valuable therapeutic option, but ADA may guarantee a better persistence in treatment. These data need to be confirmed in larger series.

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