Introduction

​Post-ERCP pancreatitis (PEP) is still the most common major complication of ERCP despite technical advancements and meticulous patient selection. The efficacy of the existing techniques is conflicting.

Aims & Methods

We aimed to compare the efficacy of peripapillary epinephrine injection in combination with rectal diclofenac for the prevention of PEP in high-risk patients .
Methods Between January 2023 and August 2023, a total of 378 patients were enrolled. We calculated that 189 patients in each group (rectal diclofenac – Group A and peripapillary epinephrine injection plus rectal indomethacin – Group B) would suffice based on a previous study by our group (α:0.05, 80% power). Patients with a non-naive papillae, ampulla of Vater cancer, biliary pancreatitis, altered anatomy, pregnancy, and pancreatic diseases such as chronic pancreatitis were excluded. Patients were assigned in a 1:1 simple randomized fashion. The primary outcome was the rate of PEP. Secondary outcomes were the rate of hyperamylasemia and rates of other adverse events.

Results

​Demographic characteristics, indications, and procedure-related risk factors were similar between the groups. The overall success rate of selective cannulation was 99.2% in Group A and 99.3% in Group B (p=0.997). PEP occurred in 9 of the 189 (4.8%) patients in Group A and 2 of the 189 (0.5%) patients in Group B. All cases were mild and managed conservatively. The rate of post-procedure 4th-hour hyperamylasemia was significantly higher in Group A (19% vs 5%, p<0.001). Postsphincterotomy-related bleeding developed in 5 patients in Group A (2.64%) but none of the patients had bleeding in Group B. Stapfer type-II perforation occurred in two patients in each group. No major cardiac adverse events-related to epinephrine injection were detected in Group B.

Conclusion

Compared to rectal diclofenac, peripapillary epinephrine injection significantly reduced the incidence of PEP, post-procedure hyperamylasemia, and sphincterotomy-related bleeding.

Clinical Case Summary

Aim: Abdominal Cocoon syndrome is the complete or partial wrapping of the abdominal organs with a membrane structure. Diagnosis can be made by laparoscopy. Patients mostly present with acute abdomen symptoms due to intestinal obstruction.
Case: 27-year-old male patient had recurrent abdominal pain for 12 years and was diagnosed with Behçet's disease and started on treatment. The patient’s abdominal pain increased in the last 6 months. He was followed up 4 months ago with suspected ileus, recovered with symptomatic treatments. A colonoscopy was performed and aphthous ulcers were detected in the terminal ileum and linear ulcers in the sigmoid colon. Tuberculosis,vasculitis and amyloid was excluded in the biopsies .With the preliminary diagnosis of Crohn's disease, 5-ASA and Azathioprine were started, and when no clinical response was obtained, Adalimumab was switched. The patient, who had no history of alcohol, cigarette use or any surgery, stopped all of her medications because she had not had symptomatic improvement for a long time, and was relieved by vomiting voluntarily. Her family history included rheumatoid arthritis in her sister and ulcerative colitis in her cousin. In the physical examination, there was no pathology other than widespread tenderness in the abdomen. In the ultrasonography; the small intestine walls were seem to be slightly edematous and retracted. Enteroscopy was completely normal. In the CT-Enterography, it was thought that it could be an "abdominal cocoon", so a laparotomy was performed and the diagnosis. The small intestines were freed from the fibrotic bands. The patient did not develop any post-operative complications, and her abdominal pain completely resolved after the operation.
Conclusion: Abdominal cocoon syndrome should be kept in mind as a very rare disease that can cause diagnostic confusion, remain undiagnosed for a long time, and cause unnecessary treatments, and can be fixed totally with surgical treatment.

Introduction

Mirikizumab (MIRI) is an anti-IL-23p19 antibody with demonstrated efficacy compared to placebo (PBO) in the treatment of moderately-to-severely active ulcerative colitis (UC) (LUCENT-1: NCT03518086; LUCENT-2: NCT03524092).¹ Prevention of IBD-related surgery and hospitalizations is a goal in disease-modification trials for preventing disease progression.² We described the rates of these events in the LUCENT-1 and -2 trials.

Aims & Methods

Patients were randomized to intravenous MIRI 300 mg or PBO every 4 weeks (Q4W) for induction in LUCENT-1. Patients randomized to MIRI induction and achieving clinical response at Week (W)12 were re-randomized 2:1 in LUCENT-2 to subcutaneous MIRI 200 mg Q4W or PBO (MIRI withdrawal) for maintenance (W12-52). Descriptive statistics were used for proportion of patients in LUCENT-1 and -2 who had hospitalization and/or surgery by treatment group and the exposure-adjusted incident rate (IR). For LUCENT-1, hospitalizations in the induction period and surgeries during the induction and 16-week follow-up period were included. For LUCENT-2, all events were from the on-treatment period. Only hospitalizations associated with an adverse event with ≥24-hour stay (for any causes) were recorded.

Results

MIRI-treated patients had significantly lower IR of overall hospitalization, UC-related hospitalization, and overall surgery vs PBO-treated patients in LUCENT-1 (IR ratio MIRI vs PBO: 0.4, 0.1, 0.4, respectively). IR of UC-related surgery was 1.3 per 100 patient-years in MIRI-treated patients vs 2.6 per 100 patient-years in PBO group (Table). Mean time to first surgery or hospitalization from randomization was 30.5 days for PBO and 58.7 days for MIRI. Additional analyses revealed that patients on MIRI who had surgery/hospitalization in LUCENT-1 or -2 tended to have prior biologic failure and longer duration of disease. Similarly, in LUCENT-2, MIRI-treated patients had significantly lower IR of all-cause hospitalization and similar all-cause surgery vs PBO. No UC-related hospitalization and surgery were reported in the MIRI group while 2 UC-related hospitalizations (1.8 per 100 person-years) were reported from PBO.

Conclusion

Lower rates of UC-related hospitalizations and UC-related surgery were observed in patients treated with MIRI compared to those treated with PBO during the 12W induction LUCENT-1, and that impact continued through the 40W of maintenance LUCENT-2 with no UC-related hospitalizations or UC-related surgery reported in MIRI-treated patients.

References

1. D’Haens G, et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. New England Journal of Medicine 2023;388(26):2444-2455.
2. Le Berre C, Peyrin-Biroulet L. Selecting End Points for Disease-Modification Trials in Inflammatory Bowel Disease: the SPIRIT Consensus From the IOIBD. Gastroenterology 2021;160(5):1452-1460.e21.

Disclosure

MR serves as a consultant and on advisory boards for AbbVie, Janssen, Bristol-Myers Squibb, UCB, Takeda, Pfizer, Prometheus Laboratories, Lilly, Celgene, and Amgen.
LPB has served as a consultant for AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax; he received grants from Takeda, Fresenius Kabi, Celltrion; he served as a speaker for Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, Medac; he also declares support travel by Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Gossamer Bio, Sandoz, MSD, Amgen, Lilly, Gilead, Thermo Fisher, Medac, CONNECT Biopharm; he declares stock options of Clinical trials Mobile Application.
JW, BZ, IR, KT, CO are employees and minor shareholders of Eli Lilly and Company.
SN has served on advisory board and speaker for Eli Lilly and Company, Pfizer and advisory board for madrigal and speaker for Janssen
TK has served as a paid consultant for Abbvie, Amgen, Biogen, Mundipharma, Hospira, Gilead, Janssen, Pfizer, MSD Sharp & Dome GmbH, and Novartis. He has received reimbursement of meeting participation fees and of travel and accommodation expenses from Abbvie, Janssen, MSD, and Takeda. He has received honoraria for preparing continuing medical education events from Abbvie, Falk, Janssen, MSD, Takeda, and Ferring Arzneimittel GmbH.
LM reports educational grants from Abbvie, Janssen, Pfizer and Takeda; advisory boards: AbbVie, Bristol Myers Squibb, Janssen, and Celltrion; consultant for Abbvie, Pfizer and Pharmacosmos.
FM has served as a speaker and received honoraria from Merck Sharp & Dohme, Abbvie, Vifor, Falk, Laboratorios Vitoria, Ferring, Hospira, and Biogen.

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.