Introduction

After first anti-TNFɑ (aTNF) failure in ulcerative colitis (UC), switching to a different mechanism of action (MoA) could decrease the rates of failure and discontinuation compared to a second aTNF and with a better safety profile.

Aims & Methods

We performed a retrospective and multicenter study (6 Andalusian sites). Patients diagnosed of UC who had failed a first biological therapy with an aTNF and started a second-line biological therapy with another aTNF or a different MoA such as ustekinumab (UST), vedolizumab (VDZ), tofacitinib and filgobinib (JAK) were included. The aim of our study was to evaluate the long-term durability of a different MoA compared to a second aTNF after a first-line therapy failure with aTNF.

Results

185 patients with UC were included. There were no significant differences between both groups in terms of age, sex, extension of disease, extraintestinal manifestations or IMIDs, smoking habit or HLA-DQA1*05. The only significant difference was disease duration (9 years MoA vs 12 years in second aTNF, p=0.02). 80 patients received a different MoA (37 VDZ, 24 UST, 19 JAK) and 105 a second aTNF (34 IFX, 60 ADA, 11 golimumab). Duration of first aTNF, although non-significant (p=0.06), tended to be shorter in the MoA group (7 months vs 12 months in aTNF group). The most frequent cause of suspension of first aTNF in the MoA group was primary failure (46% vs 31%, p= 0.02) and in the second aTNF group was secondary failure (51% vs 35%, p=0.02). The follow-up mean was 22.4 months in the group of a different MoA and 23.3 months in the second aTNF group. 60% of patients discontinued the second-line biological treatment, 64% with aTNF vs 35% with a different MoA. Durability of therapies in the group of different MoA was significatively longer compared with second aTNF (50% vs 31.4%, p=0.036) (figure 1). UST showed the best durability (66.7%), followed by JAK (63.2%), IFX (52.9%), VDZ (32.4%), ADA (21.7%) and golimumab (18.2%), with significant differences (p=0.03). Reasons for discontinuation were primary failure in 29.7% (63.6% second aTNF vs 36.4% different MoA), secondary failure in 25.9% (64.5% second aTNF vs 35.5% different MoA) and intolerance or adverse events in 6.4% (66.6% second aTNF vs 34.4% different MoA). Adverse events were reported in 12 patients, 8 with aTNF a 4 with other MoA (2 vs 0 infusion reactions, 1 vs 1 mild infections, 2 vs 1 respiratory adverse effects, 1 vs 1 cutaneous reactions, 1 vs 0 musculoskeletal effects, 1 vs 1 neoplasia).

Conclusion

Our study shows that after a first aTNF failure in UC, a switch to a biological therapy with a different MoA achieves longer survival compared to switching to a second aTNF, with less primary and secondary failure.

Introduction

Patients suffering from ulcerative colitis (UC) have reduced life qualities and an increased risk of developing cancer. Current treatment options are limited and have a ceiling effect with remission rates of ~35%. A possible reason is the multi-factorial aetiology, which are associated with an overactivation of the immune system and a dysbiosis of the gut microbiome. An important step towards a better understanding is the characterization of epithelial lesions. Their severity is classified by the Mayo score system based on their macroscopic appearance. While previous studies analysed cellular changes within the colon in UC patients, a detailed characterization of different UC-associated lesions are still missing, which is the aim of our study in collaboration with Sanofi Pharmaceuticals.

Aims & Methods

We recruit patients with active disease at our endoscopy unit and collect different biopsies from multiple regions within these patients to compare the reproducibility of single cell RNA sequencing (scRNAseq) results of similar appearing lesions within and between patients. For the sample preparation, we performed a cellular enrichment step for immune, epithelial and stromal cells before performing 10x scRNAseq to obtain equal numbers for each cell fraction from every sampled area. Additionally, we collected stool samples and endoscopic brushes to determine the associated microbial communities by 16S rRNA sequencing.

Results

Our cellular isolation strategy allows successful recovery of fibroblast, epithelial and immune cell fractions from each lesion. All expected epithelial cell types as previously described are detected in our dataset as well. Moreover, our experimental setup to obtain comparable numbers of fibroblasts, epithelial and immune cells enables us now to investigate cell-cell communication differences within different Mayo score lesions. For example, CXCL signals increased with the severity of macroscopic lesions and involves multiple cell types. Additionally, we are in the middle of correlating microbial diversity with the corresponding disease conditions.

Conclusion

Our results provide exciting insights into cell-cell communications at an unprecedented depth, which identifies aberrant signalling pathway that may contribute to treatment failure in the clinics.

Disclosure

We have nothing to disclose

Introduction

The STRIDE II guidelines recognize endoscopic healing (EH), defined by an SES-CD score ≤2 or a CDEIS score <3, as one of the main therapeutic targets in Crohn's disease (CD). Nevertheless, complete EH could reduce the risk of long-term complications in CD. The aim of this study was to assess the risk of long-term complications in CD according to the degree of EH achieved.

Aims & Methods

We conducted a prospective multicenter study that included all patients with CD undergoing colonoscopy for EH assessment between September 2019 and September 2022 in three centers and were compared outcomes of patients with complete EH (CDEIS = 0) vs partial EH (CDEIS greater than 0 but less than 4). The primary endpoint was therapeutic failure, defined as the need for drug intensification and/or corticosteroid initiation and/or CD-related hospitalization and/or development of a luminal strictures/fistula and/or perianal CD and/or the need for intestinal resection.

Results

A total of 128 patients were included with a median disease duration of 10 (IQR, 4-18) years. Fifty-six (43%) patients had ileocolonic location and 79 (62%) an inflammatory (B1) behavior. Patients had been on treatment for a median of 12 months (8.3-24.3) prior to colonoscopy and 81 (63%) patients had complete EH. After a median follow-up of 22.5 months [IQR, 19.3-23.7], therapeutic failure was observed in 40 patients (31%). The risk of therapeutic failure was significantly higher among patients with partial EH group (25% vs. 43% p = 0.036, HR = 1.90; IC95% = [1.02 - 3.53]; p=0.043). The risk of CD-related hospitalizations (2.5% vs. 17%), p=0.005, HR= 7.09; IC95% = [1.51 – 33.4]; p=0.013) was significantly higher in patients with partial EH. The risk of intestinal resection, steroid initiation and drug intensification among patients with complete and partial EH, were 0% vs. 4.3% (p=0.13), 2.5% vs. 11% (p=0.1) and 22% vs. 36% (p=0.088), respectively.

Conclusion

This prospective multicenter study confirms that complete endoscopic healing is associated with better long-term outcomes than partial endoscopic healing in patients with CD, as well as fewer hospitalizations and an overall decreased risk of treatment failure.

Introduction

Crohn's disease (CD) and ulcerative colitis (UC) are the most common types of IBD. CD and UC are practically indistinguishable at early stages, which makes its diagnostics difficult. Various molecular methods are designed to carry out for global search of the most informative markers for IBD types verification and CD and UC differential diagnosis. Among omics technologies, metabolomics, as one of the promising tools that can contribute to the search and rapid implementation of informative markers. Today, various options are available for the assessment of low molecular weight compounds, such as HPLC-MS/MS, GC-MS/MS, etc. In this study, we combined the search for metabolomic markers using HPLC-MS/MS and HS GC-MS/MS methods for analyzing such groups of metabolites as lipids, volatile metabolites and hydrophilic metabolites in serum and stool samples from Crohn's disease and ulcerative colitis patients.

Aims & Methods

The study was conducted for groups of patients with a verified diagnosis of Crohn's disease and ulcerative colitis. Serum and stool samples were obtained from patients in a hospital. Informed consent for the study was obtained from all patients. The total number of serum and stool samples was 160 samples (CD and UC combined). The samples were provided by the Department of Gastroenterology of the M.F. Vladimirskiy Moscow Regional Research and Clinical Institute, Moscow, Russia., as well as the Department of Gastroenterology of the LOPUKHIN FRCC PCM. Lipid and hydrophilic fractions of metabolites extracted from serum was carried out using HPLC-MS TripleTOF 6600+ System. Stool samples were analyzed using a Shimadzu QP2010 Ultra GC/MS with a Shimadzu HS-20 headspace extractor.

Results

Stool samples analysis shown that isovaleric acid is one of the markers for the IBD and the ratio of valeric and isovaleric acids using the logistic regression method allows us to obtain a risk coefficient for the IBD development. Analysis of the serum hydrophilic fraction demonstrated quantitative difference for the following compounds: Sphingosine, Urocanic Acid, N-Acetylcytidine, 5'-S-Methylthioadenosine, Adenine, -Hydroxyanthranilic acid, Acetylcarnitine, O-Acetyl-L-carnitine, Nicotinamide, Phenylalanine, Isoleucine, Choline chloride, Proline, Cholic acid_CA, Chenodeoxycholic acid, Inosine, Glycoursodeoxycholic acid. Mentioned markers contributed to the IBD verification, while O-Acetyl-L-carnitine contribute to the differentiation between Crohn's disease and ulcerative colitis. When analyzing the lipid fraction, differences were identified for a limited range of lipids, however, such lipids as Cer 37:0;3O|Cer 20:0;2O/17:0;O, PE P-36:2|PE P-18:0_18 :2 and PC 36:2|PC 18:1_18:1 were detected only in CD samples.

Conclusion

The obtained metabolomic differences in the hydrophilic fraction and volatile components make it possible to reliably verify inflammatory bowel diseases, since separate lipid markers and O-Acetyl-L-carnitine contribute to the CD detection.