Introduction

Malignancies involving the duodenum, major papilla, head of the pancreas and distal common bile duct can lead to malignant biliary and gastric outlet obstruction. When clinical presentation of biliary and duodenal obstruction is simultaneous, these tumors are usually at the late stage of the disease and the only option is palliative treatment to improve the quality of life of these patients.

Aims & Methods

We describe a dual biliary and digestive tract drainage by endoscopic ultrasound (EUS) in a patient with metastatic squamous cell carcinoma (SCC) of the cervix causing dilation of the bile duct, bulb and stomach with sleeve infiltration at the level of the hepatic hilum and duodenal arch.

Results

A 67-year-old woman, performance status 0, diagnosed with SCC of the cervix in 2022 underwent curative treatment. In February 2024 was admitted due to jaundice and vomiting progressing for 2 months. Computed tomography revealed dilatation of the bile duct, bulb and stomach with sleeve infiltration of the duodenal arch. Endoscopic ultrasound (EUS) identified a heterogeneous lesion causing obstruction of the middle third of the bile duct, confirming the diagnosis of metastatic SCC of the cervix. After discussion with multidisciplinary team, the patient was proposed for palliative treatment. Subsequently, she underwent EUS-guided gastrojejunostomy with placement of a 20x10mm lumen-apposing metal stent (LAMS). Bile duct drainage wasn’t done due to absence of bile duct dilatation over 12mm as the total bilirubin levels frankly decreased with corticotherapy. However, a week later, the total bilirubin levels increased and a biliary drainage was proposed, attempting access to the papilla through gastrojejunostomy, a procedure complicated by migration of the gastric end of the LAMS into the peritoneal cavity. The guidewire was immediately placed, the LAMS was mobilized into the stomach, concurrently initiating broad-spectrum antibiotic therapy. Despite this initial event, it was decided to proceed with EUS-guided choledocoduodenostomy after identifying the bile duct, placing a 6x8mm LAMS with the distal end released outside the bile duct and positioning a fully covered 40x10mm metal biliary stent coaxially to the LAMS as a rescue, with the end below the confluence and no evidence of contrast extravasation on fluoroscopy. The procedure was complicated by respiratory distress with symptomatic relief after pneumoperitoneum drainage. Recovery was uneventfully and the patient was discharged 5 days after biliary drainage and is well after 30 days of follow up.

Conclusion

EUS guided procedures such as biliary drainage and gastrojejunostomy are likely to spread quickly in clinical practice for the treatment of concomitant malignant biliary and gastric outlet obstruction. The following case is presented due to the importance of recognizing and managing intraprocedural complications associated with LAMS.

References

Rizzo GEM, Carrozza L, Quintini D, Ligresti D, Traina M, Tarantino I. A Systematic Review of Endoscopic Treatments for Concomitant Malignant Biliary Obstruction and Malignant Gastric Outlet Obstruction and the Outstanding Role of Endoscopic Ultrasound-Guided Therapies. Cancers (Basel). 2023 Apr 30;15(9):2585.

Introduction

Factors influencing the exposure to targeted therapies (biologics/JAKi), intestinal resections and hospitalisations in newly diagnosed IBD patients have been scarcely studied.

Aims & Methods

Aim: To identify predictive factors of exposure to biologics/JAKi, surgeries, and hospitalisations within the first five years in IBD patients.
Methods: Prospective, population-based, nationwide registry. Adult patients diagnosed with IBD [Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)] during 2017 in the 17 Spanish regions were included. Patients who consented were followed-up for 5 years after diagnosis. Multivariate analyses were performed to identify the predictive factors for biologics/JAKi use, surgeries, and hospitalisations. To this end, only abdominal surgeries were analysed, and early treatment with immunomodulators or biologics/JAKi drugs were considered if these had been prescribed within the first six months of diagnosis.

Results

A total of 1,526 patients diagnosed with CD and 1,633 with UC were included. Regarding the predictors of exposure to biologics/JAKi treatments, we observed that younger age, more aggressive phenotype of CD and greater extent of UC were associated with a higher risk of exposure (table 1). Furthermore, smoking was associated with a higher likelihood of exposure to biologics/JAKi drugs in patients with CD (HR=1.33, 95%CI=1.11-1.60) while in UC patients it was associated with a lower risk (HR=0.56, 95%CI=0.35-0.89). Concerning surgeries (table 1), early treatment with immunomodulators was associated with a lower risk in patients with CD (HR=0.33, 95%CI=0.22-0.49), whereas early use of biologics/JAKi drugs was associated with a higher likelihood of surgery in patients with UC (HR=11.86, 95%CI=4.62-30.42). Finally, the exposure to biologics/JAKi drugs was associated with a lower risk of hospital admissions both in patients with CD (HR=0.37, 95%CI=0.24-0.56) and UC (HR=0.45, 95%CI=0.22-0.91) (table 1).

Table 1: Predictors of biologics/JAKi use (A), surgeries (B) and hospitalisations (C) in patients with Corhn´s disease (CD) and ulcerative colitis (UC)

Conclusion

The exposure to biologics/JAKi drugs is mediated by the more aggressive phenotype of CD, greater extent of UC, and younger patient age. The use of biologics/JAKi drugs, as currently practiced, is associated with a lower risk of hospitalisations but does not reduce the need for surgery, even when administered early. There is an unmet need for more accurate identification of patients who require these treatments to modify the natural course of the disease.

Disclosure

SR has received support for conference attendance, speaker fees, research support, and consulting fees from AbbVie, Adacyte, Faes Pharma, Ferring, Tillots, Galapagos, Janssen, Pfizer, and Lilly.
RF has received support for conference attendance, and research support from AbbVie, Faes Pharma, Ferring, Janssen, Pfizer, Takeda, and Galapagos.
RC: has received support from Janssen, Johnson&Johnson, Ferring, Abbvie, Falk, Pfizer y Galápagos.
AN: has received financial support for travelling and educational activities from Pfizer, Abbvie, Takeda, Janssen, Tillotts Pharma and Ferring.
JPG has served as a speaker, a consultant and advisory member for or has received research funding from MSD, Abbvie, Hospira, Pfizer, Kern Pharma, Biogen, Takeda, Janssen, Roche, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Vifor Pharma.
MC has served as a speaker, or has received research or education funding from MSD, Abbvie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma.

Introduction

Targeted therapies have revolutionized the management of immune-mediated inflammatory diseases (IMIDs), however, there is a substantial number of patients who respond poorly to a given drug. There is a big need to understand the factors that are associated with this heterogeneity.

Aims & Methods

The DoCTIS project (1) aims to characterize molecular variation both at the disease and drug response levels across six different IMIDs. We applied single cell RNA sequencing to 360 peripheral blood mononuclear cell (PBMC) samples from 176 patients from six prevalent IMIDs –psoriasis (PS), psoriatic arthritis (PsA), Crohn’s Disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE)- treated with five different drugs targeting TNF, IL12p40, IL6R, BLySS, IL17 and JAK pathways. All patients were analyzed at two time points including baseline and at the week of clinical response creating an immune landscape of more than two million peripheral immune cells.

Results

We found large inter-disease differences both at the compositional and genetic regulatory programs. ScRNA-Seq analysis revealed large differences at the systemic level between the six IMIDs. Compositional analyses demonstrated that the circulating immune cell profiles of UC and CD were more similar to each other than to the rest of IMIDs, and also identified differences in pDC, MAIT, NK CD16- and T CD4+ Memory subsets between both diseases. At the transcriptional level, we found the expected upregulated interferon response signature affecting multiple cell types in SLE, but also novel findings like strong regulatory differences in B and CD14+ monocyte compartments between UC and CD, two diseases with a highly shared genetic risk. The impact of each drug was found to be largely disease-specific. Furthermore, we found multiple regulatory features associated with the effect of each drug as well the association to response.

Conclusion

The scRNA-Seq atlas developed in DoCTIS provides a unique resource for the understanding of drug response and disease heterogeneity across immune-mediated inflammatory diseases.

References

1. Decision on Optimal Combinatorial Therapies in IMIDS using Systems Approaches (DoCTIS). https://doctis.eu/

Disclosure

Antonio Julià: None declared, Yolanda Guillén: None declared, Paloma Vela Casasempere: None declared, Antonio Fernández Nebro: None declared, Carlos Marras: None declared, Santos Castañeda Bristol-Myers Squibb, Eli Lilly, Bristol-Myers Squibb, Jaime Calvo Alén: None declared, Jesús Tornero Molina: None declared, Juan de Dios Cañete Crespillo: None declared, Eugeni Domènech: None declared, Javier Gisbert: None declared, Jose M Carrascosa: None declared, Eduardo Fonseca: None declared, Luis Bujanda Fernández de Pierola: None declared, Valle García Sánchez: None declared, Britta Siegmund: AbbVie, AlfaSigma, BMS, CED Service GmbH, Dr. Falk Pharma, Eli Lilly, MSD, Ferring, Galapagos, Janssen, Pfizer, and Takeda, Abivax, Boehringer Ingelheim, Endpoint Health, Gilead, Janssen, Landos, Materia Prima, PredictImmune, Giampiero Girolomoni: AbbVie, Almirall, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli-Lilly, Leo Pharma, Merck Serono, Novartis, Pfizer, Pierre Fabre, Samsung bioepis and Sanofi, Almirall, Amgen, Bristol-Myers Squibb, Eli-Lilly, Leo Pharma, Merck Serono, Novartis, Pfizer, Samsung bioepis and Sanofi, Pfizer, Holger Heyn: Mirxes, Moderna, Nanostring, Omniscope, Singularity, Laura Jimenez: None declared, Pere Santamaría: None declared, Edgar Angelats: None declared, Rick Myers: None declared, Sergio H. Martínez-Mateu: None declared, Juan Angel Patiño Galindo: None declared, Ernest Choy: AbbVie, Amgen, Biocon, Biogen, Chugai, Eli Lilly, Fresenus Kabi, Gilead, Janssen, Novartis, Pfizer, Regeneron, Roche, RPharm, and Sanofi, Bio-Cancer, Biogen, Novartis, PFizer, and Sanofi, AbbVie, Amgen, Bristol-Myers Squibb, Chugai, Eli Lilly, Fresenus Kabi, Galapagos, Gilead, Novartis, Pfizer, Regeneron, Roche, RPharm, Sanofi, and UCB Pharma, Sara Marsal: None declared

Introduction

Following anti-TNF therapy, treatment options include switching between different anti-TNF agents or swapping to therapies with distinct mechanisms of action. It is essential to evaluate these treatment pathways in real-world settings to improve inflammatory bowel diseases (IBD) management.

Aims & Methods

This retrospective study analyzed data from the French National Health Data System and included all adult patients meeting at least one of the following criteria between 2014 and 2023: i) long-term disease related to IBD ii) at least 2 hospitalizations for IBD iii) one hospitalization for IBD coupled with 3 or more IBD treatment deliveries. The study assessed treatment discontinuation (short-term: 1 year; long-term: 5 years), and hospitalizations for IBD, IBD-related surgeries and serious infections among patients initiating a second line treatment (2L) between 2014 and 2022 following a first anti-TNF therapy. All outcomes were evaluated one year post switching between anti-TNF agents (reference) versus swapping to vedolizumab (VDZ) or ustekinumab (UST) using a propensity score (PS)-matched Cox proportional hazards model. Covariates used to estimate PS were age, gender, and medical history (see full list in Table 1). Covariate balance was assessed through standardized mean difference (SMD).

Results

The cohort consisted of 151,999 CD patients and 152,367 UC patients, with 14.5% of CD patients and 9.3% of UC patients undergoing 2L treatment. After PS matching, the profiles of IBD patients who switched to a 2^nd anti-TNF were comparable to those who swapped to UST or VDZ (SMD<0.1 for all covariates). Main outcomes are summarized in Table 1.
CD patients who swapped to VDZ had higher risks of treatment discontinuation compared to those who switched to a 2^nd anti-TNF (short-term: adjusted hazard ratio (aHR)=1.23 95%CI [1.11-1.36]; long-term: aHR=1.14 95%CI [1.06-1.23]). Conversely, patients who swapped to UST showed lower risks of treatment discontinuation (short-term: aHR=0.76 95%CI [0.70-0.81]; long-term: aHR=0.72 95%CI [0.68-0.76]), and experienced fewer hospitalizations due to IBD (aHR=0.77 95%CI [0.71-0.83]) and serious infections (aHR=0.74 95%CI [0.59-0.93]).
UC patients who swapped to VDZ had lower risks of treatment discontinuation (short-term: aHR=0.81 95%CI [0.75-0.87]; long-term: aHR=0.83 95%CI [0.78-0.87]), but a higher risk of IBD-related hospitalizations (aHR=1.11 95%CI [1.02-1.20]) compared to those who switched to another anti-TNF. In contrast, UC patients who swapped to UST showed decreased risks of treatment discontinuation (short term: aHR=0.58 95%CI [0.49-0.69]; long-term: aHR=0.62 95%CI [0.54-0.71]). For all other outcomes, the results were statistically non-significant and are presented in Table 1.

Conclusion

In this large cohort of patients, swapping to UST led to better treatment persistence in both CD and UC while reducing the risks of hospitalizations and serious infections in CD compared to switching between anti-TNF agents. Swapping to VDZ offered better treatment persistence than switching to another anti-TNF agent in UC.

Disclosure

LV received fees from abbvie, amgen, MSD, Ferring, Takeda, Pfizer, Janssen, Lilly, Galapagos, Celltrion, Viatris
LPB received fees from Abbvie, Abivax, 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, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD
Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par' Immune, Pfizer, Prometheus,
Protagonist, Roche, Roivant, Samsung, Sandoz, Sanofi, Takeda, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vifor, Vectivbio,
Ventyx, Ysopia.
JK received fees from Janssen, Takeda, Lilly, Abbvie, Pfizer, Tillots, Amgen, Celltrion, Roche, Gilead, Galapagos.
SC, VC, HO, LG, KS, LC works for Johnson&Johnson Innovative Medicine.
PR, GB, AH, TN works for IQVIA Operations France.