Introduction

Self-expandable metallic stents (SEMS) are commonly used to relive malignant gastric outlet obstruction (GOO). However, SEMS with high radial force can occurs tissue proliferation caused by mechanical injury. To overcome these problems, drug-eluting stents using antiproliferative drugs have been developed. Specially, everolimus have demonstrated efficacy in reducing restenosis rates in arteries, but their potential application in the gastrointestinal tract remains unexplored. Additionally, recent studies have reported that stents with thinner struts have a reduced risk of clinical restenosis compared to stents with thicker struts. However, the application of everolimus-coated laser-cut stents, which offer robust antiproliferative properties, has not yet been investigated or established in the gastrointestinal tract.

Aims & Methods

This study aims to investigate the efficacy and safety of everolimus-coated laser-cut SEMS in suppressing stent-induced tissue hyperplasia in a rat gastric outlet model.
Everolimus-coated laser-cut SEMS were prepared using ultrasonic spray technology, and the characteristics of the SEMS before and after coating process were evaluated. Twelve male rats were randomly divided into two groups: control (laser-cut SEMS, n = 6) and everolimus (everolimus-coated laser-cut SEMS, n = 6). The effectiveness of everolimus-coated laser-cut SEMS were assessed by comparing results of fluoroscopy, endoscopy, and histopathological analyses.

Results

Everolimus were uniformly coated onto the surface of the laser-cut SEMS and approximately 80% of everolimus was slowly released for a week. Stent placement was successful in all rats. Stent-induced tissue hyperplasia variables were significantly lower in the everolimus group compared to the control group (all p < 0.05). The luminal diameter was significantly larger in the everolimus group than in the control group (p < 0.05). The degrees of α-SMA-, Ki-67-, and BrdU-positive deposition were significantly lower in the everolimus group (p < 0.001), while the degree of TUNEL-positive deposition was significantly higher than in the control group (p < 0.001).

Conclusion

Everolimus-coated laser-cut SEMS effectively suppressed stent-induced tissue hyperplasia in a rat gastric outlet model. Local treatment with everolimu via laser-cut SEMS was safe and effective to maintain the stent patency and has therapeutic potential in the prevention of restenosis after stent placement in the gastrointestinal tract.

Disclosure

No disclosure

Introduction

Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that potently neutralizes IL-23 and binds to CD64, a receptor on cells that produce IL-23.¹ In the Phase 3 QUASAR maintenance study (NCT04033445), both the GUS 100mg every 8 weeks (q8w) and 200mg q4w subcutaneous (SC) maintenance dose regimens were efficacious.² Here, we evaluated efficacy of these dose regimens in clinically relevant subgroups of participants (pts) with and without extensive ulcerative colitis (UC) disease or high inflammatory burden.

Aims & Methods

Clinical responders after 12 weeks of GUS intravenous (IV) induction were randomized 1:1:1 to GUS 100mg SC q8w, GUS 200mg SC q4w or placebo (PBO) (GUS withdrawal) at start of the maintenance study (M-0). Efficacy endpoints were analyzed at Week (W)44 in the primary analysis population of pts randomized and treated in the maintenance study who had a modified Mayo score of 5-9 at induction baseline (I-0). Subgroup analyses were conducted by (1) extent of UC disease (limited to left side of colon vs extensive) based on screening endoscopy and/or medical history at I-0 and (2) inflammatory burden based on serum C-reactive protein (CRP) levels (≤3 vs >3mg/L) at M-0.

Results

Of 568 pts in the primary analysis population, 257 (45.2%) had extensive UC disease at I-0 and 182 (32.0%) had serum CRP >3mg/L at M-0.
Proportions of pts achieving W44 clinical and histologic-endoscopic efficacy endpoints were greater with both GUS dose regimens vs PBO across subgroups (Table). For pts with extensive UC disease, the proportion of pts achieving clinical remission at W44 was numerically greater with GUS 200mg q4w (62.7%) relative to GUS 100mg q8w (49.4%) (PBO, 11.6%). For those with elevated CRP (>3mg/L) at M-0, clinical remission at W44 was achieved by 48.2% of GUS 200mg q4w vs 30.2% of GUS 100mg q8w pts (PBO, 14.3%). Proportions of pts achieving endoscopic improvement, histo-endoscopic improvement, endoscopic remission, and maintenance of clinical remission were also greater with GUS 200mg q4w in these subgroups. Among pts with disease limited to the left side of the colon or CRP ≤3mg/L at M-0, proportions of pts achieving these efficacy endpoints were similar with GUS 100mg q8w and GUS 200mg q4w.

Conclusion

For pts with moderately to severely active UC with extensive disease or high inflammatory burden, greater efficacy rates were observed with GUS 200mg SC q4w compared with GUS 100mg SC q8w.

References

1. Sachen KL et al. Guselkumab binding to CD64+ IL-23–producing myeloid cells enhances potency for neutralizing IL-23 signaling. Front. Immunol. 2025;16:1532852.
2. Rubin DT et al. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies. Lancet. 2025;405(10472):33-49.

Disclosure

Study support: Johnson & Johnson.​
JRA: Abbvie, Bristol Myer Squibb, Ferring, Finch, Iterative Scopes, Johnson & Johnson, Merck, Pfizer, Roivant, Seres Therapeutics and Roivant Adiso
TH: AbbVie, Bristol Myers Squibb, Daiichi-Sankyo, EA Pharma Co, Ltd., JIMRO, Eli Lilly, Gilead Sciences, Johnson & Johnson, Kissei Pharmaceutical Co, Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Inc and Takeda Pharmaceutical Co., Ltd
BB: AbbVie, Alimentiv, Allergan, Amgen, AMT, Bausch Health, Bristol Myers Squibb, Business Intelligence, Celgene, Celltrion, Eupraxia Fresenius Kabi, Ferring, Genentech/Roche, Gilead, Iterative Scopes, GlaxoSmithKline, Jamp, Johnson & Johnson, Merck, Microbiome Insights, Mylan, Novartis, Organon, Pendopharm, Pfizer, Protagonist, Qu Biologic, Sandoz, Takeda, and Viatris
LPB: AbbVie, Abivax, Adacyte, Alimentiv, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Bristol Myers Squibb, Celltrion, Connect, Cytoki, Eli Lilly, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech/Roche, Gilead, Gossamer Bio, GlaxoSmithKline, HAC-Pharma, IAG, InDex, Inotrem, Johnson & Johnson, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Nordic Pharma, Novartis, OM, ONO, OSE, Pandion, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Roivant, Samsung, Sandoz, Sanofi, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Vectivbio, Ventyx, Viatris, Vifor, and Ysopia
MG, SY, NS, YM: Johnson & Johnson.
BES: AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Celltrion, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Johnson & Johnson, Kaleido, Kallyope, Lilly, Merck, Microba, Mirador Therapeutics, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Sorriso Pharmaceuticals, Spyre Therapeutics, Sun Pharma, Surrozen, Takeda, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences, and Vividion Therapeutics
DTR: Abbvie, Altrubio, Apex, Avalo Therapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Johnson & Johnson, Lilly, Pfizer, Samsung Neurologica, and Takeda.
AD: Abivax, AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, CED Service GmbH, Celltrion, Dr Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Gilead, High5MD, Johnson & Johnson, Lilly, Materia Prima, MedToday, MSD, Pfizer, Pharmacosmos, Roche, Sandoz, Stada, Takeda, Thieme, Tillotts, UniMed Verlag and Vifor Pharma

Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder from the atopic disease spectre. Despite being studied for years, the EoE-specific therapy has been approved only recently and includes budesonide orodispersible tablet (1) and IL-4R antagonist, dupilumab (2). Therefore, data on the management of the patients who do not respond to this treatment is scarce. Especially those who were diagnosed long in the past and have undergone different therapeutical approaches remain an understudied group. The aim of this project was to provide information on the treatment courses in a real-world setting over past 10 years.

Aims & Methods

This was a retrospective nation-wide project collecting data on patients with EoE in 7 Austrian centres since January 2014. The last follow-up was marked as of February 2025. Information on patients’ demographics, previous medical history, number of esophageal food impactions and different treatment lines were recorded. Due to the descriptive character of the work, no power analysis was carried out.

Results

In total, 336 patients (30.1% female) were included. Approximately one third of them (119/336) experienced an esophageal food impaction before the diagnosis was made. The most common 1st line therapy was budesonide orodispersible tablet (193/336, 57.4%), followed by proton pump inhibitors (87/336, 25.9%) and food elimination diet (20/336, 6.0%). Two hundred twenty (220/336, 65.5%) patients did not remain on the 1^st line treatment. Forty-four (44/336, 13.1%) subjects required more than 2 therapies and one person received even 7^th line medication. Biologic treatment – dupilumab – was given to forty-one (12.2%) patients. It was the first line treatment in 1 person, the others received it in the further course. These drugs were well-tolerated and 97.6% (40/41) patients remained on it until the last follow-up and reached symptomatic remission. Three patients were diagnosed more than 10 years before they received biologic treatment and 2 of them responded to it. One person discontinued due to side effects. The most common reasons for switch for dupilumab were clinical and/or histological activity (24/41, 58.5%), side effects (10/41, 24.4%) and patients’ preference (2/41, 4.9%).

Conclusion

This is the first study on different therapy courses in patients with EoE in Europe. Due to its retrospective character, no direct conclusions on the superiority of one approach upon another in case of refractoriness are possible.

References

1. Lucendo AJ, Miehlke S, Schlag C, Vieth M, von Arnim U, Molina-Infante J, et al. Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial. Gastroenterology. 2019;157(1):74-86.e15.
2. Hirano I, Dellon ES, Hamilton JD, Collins MH, Peterson K, Chehade M, et al. Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis. Gastroenterology. 2020;158(1):111-22.e10.

Disclosure

JP: travel grants from Johnson&Johnson and Tillots Pharma AG
MW: no conflicts of interest
PD: consulting and speakers fees from Falk Pharma, Sanofi, Abbvie, MSD, Takeda, Janssen, Pfizer
KS: support from: Abbvie, Astro Pharma, Takeda, Johnson&Johnson, MSD, Falk Pharma, Galapagos
TH: speaker fee from Falk
MH: no conflicts of interest
LKS: •Past/present Principal investigator für Studien gesponsort durch: SigmaTau, Sanofi , Tigenix und Falk;
•Speaker fee: MSD, AbbVie, Ferring, MerckSerono/Dr Falk, Chiesi, Novartis, Roche, Abbott, Phadia Austria/Thermo Fisher Scientific, CSL-Behring , Janssen-Cilag Pharma, Labors.at GmbH, Vertex, ENML Laborbetriebs GmbH, Johnson&Johnson
•Conference support: Mylan, Abbott, MSD, Gilead, MerckSerono/Dr Falk, Novartis, Pfizer, Janssen-Cilag Pharma, Chiesi, Shire, Abbvie, Takeda, Vertex, Astropharma
•Consultancy for: MSD, Takeda
GN: lecturing fees, consulting fees, and advisory fees from AbbVie, Merck Sharp & Dohme, Takeda, Janssen-Cilag, Pfizer, Gilead, Galapagos, Ferring, Vifor, AstroPharma, Falk, Bristol Myers Squibb, Arena Pharmaceuticals and Amgen
MT: received grant support from Albireo, Alnylam, Cymabay, Falk, Genentech, Gilead, Intercept, MSD, Takeda and UltraGenyx, honoraria for consulting from AbbVie, Albireo, Agomab, Boehringer Ingelheim, BiomX, Chemomab, Dexoligo Therapeutics, Falk, Genfit, Gilead, GSK, Hightide, Intercept, Ipsen, Jannsen, MSD, Novartis, Phenex, Pliant, Regulus, Siemens and Shire, speaker fees from Albireo, Boehringer Ingelheim, Bristol-Myers Squibb, Falk, Gilead, Intercept, Ipsen, Madrigal, Mirum and MSD , as well as travel support from AbbVie, Falk, Gilead, Jannsen and Intercept. He is also co-inventor of patents on the medical use of 24-norursodeoxycholic acid filed by the Medical University of Graz (service inventions).
WS: no conflicts of interest
HS: consulting and speakers fees from Falk Pharma, Sanofi, Medtronic
PS: consulting fees and/or speaker fees from Dr. Falk Pharma, GmbH, Takeda, Regerenon-Sanofi Pharmaceuticals, AbbVie, Janssen-Cilag, Receptos-Celgene-BMS