Introduction

Smoking is an environmental and conductual risk factor for the development of Chron’s Disease (CD) and is associated with a more severe course of CD. In contrast, a protective effect is shown in the development and a mild course of Ulcerative Colitis (UC). Smoking leads to cardiovascular disease, cancer and other chronic diseases, and social isolation, anxiety and depression. It is also a predictor of poorer adherence to treatment in young patients.

Results & Findings

50% were women, 52 years old (SD: 12.6). 58.6% suffered CD, 39.7% more than 10 years from onset of disease, 60.7% with biologics; 54.4% in remission and 29.8% mild activity. 24% were active smokers, 60% ex-smokers and 15.5% has never smoked. 60.3% were regular exercisers, and 66% consume alcoholic beverages regularly.
Of those who smoked, 64% were women, 57% suffered CD, 46% was in remission. 85.7% with anxiety and 52.7% with depression, 61.5% perceived their health status as suboptimal. 64.3% consumed alcoholic beverages, 57.1% no physical exercise.
The mean anxiety score was 9 (SD: 3.6), depression score was 5.76 (SD: 3.7). 67.2% had anxiety levels and 32.8% depression. Perceived health status as optimal was 57.9%.
In the bilateral analysis between smoking and the independent variables, only depression and anxiety was associated.

Summary & Discussion

Smoking is an environmental risk factor for the development and course of CD. The aim of this study iis to determine smoking habits and associated factors in patients with Inflammatory Bowel Disease (IBD) in Hospital Universitario del Henares (Madrid).
A transversal study was carried out. Data were collected in a questionnaire ad-hoc and HADS.
Patients with IBD are active smokers, and their percentage is bigger to regular population in Comunidad de Madrid (21.9%). On the other hand, the percentage of ex-smokers with IBD (60%) is much higher than with no IBD; it may be related to IBD development.
It is well known the relationship between IBD and psicosocial aspects. In this study we show the high prevalence of anxiety and depression, which is higher than in general population.
Nurses can play an important role in the psychological care of patients with IBD, especially in prevention and early detection.

Conclusion

Patients with IBD showed a high tobacco consumption, most of which were women and with no healthy habits.
Smoking in patients with IBD is associated with anxiety and depression.

References

(1) Bisgaard TH, Allin KH, Keefer L, Ananthakrishnan AN, Jess T. Depression and anxiety in inflammatory bowel disease: epidemiology, mechanisms and treatment. Nat Rev Gastroenterol Hepatol. 2022;19(11):717-726.
(2) Feng L, Cai X, Zou Q, et al. Exploring the management and treatment of IBD from the perspective of psychological comorbidities. Therap Adv Gastroenterol. 2024;17:17562848241290685.
(3) Barreiro-de Acosta M, Marín-Jiménez I, Panadero A, et al. Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) and the Association of Crohn's Disease and Ulcerative Colitis Patients (ACCU) in the management of psychological problems in Inflammatory Bowel Disease patients. Gastroenterol Hepatol. 2018;41(2):118-127.
(4) Herrero MJ, Blanch J, Peri JM, et al. A validation study of the hospital anxiety and depression scale (HADS) in a Spanish population. Gen Hosp Psychiatry. 2003;25(4):277-83.
(5) Comunidad de Madrid. Dirección de Salud Pública. Resultados del Sistema de Vigilancia Integral del Tabaquismo (VITa). Informe 2023.

Introduction

TPM502 is a mixture of three distinct nanoparticles, each coupled with one celiac disease (CeD)-relevant gluten peptide, representing immunodominant and deamidated CD4⁺ T cell epitopes. TPM502 targets liver sinusoidal endothelial cells, which are unconventional antigen-presenting cells capable of inducing antigen-specific tolerance.

Aims & Methods

TCeD21 (NCT00565136) was a phase 2a double-blind, randomized, placebo-controlled study in HLA-DQ2.5-positive adults with confirmed CeD on a gluten-free diet. Patients achieving a predefined IL-2 response to a single dose (6 g) gluten challenge (GC1) were randomized into four cohorts to receive two intravenous infusions with escalating doses of TPM502 or placebo on day (D) 1 and D15. The GC was repeated 7 days after the second TPM502 dose (GC2). Peripheral blood mononuclear cells collected from each patient at predefined timepoints were analyzed by high-dimensional (30-color) flow cytometry, before and after HLA-DQ2.5-gliadin-specific tetramer (tet) enrichment, using surface staining for various phenotypic markers. The study aimed to characterize the phenotypes of gluten-specific T cells in CeD patients before and after TPM502 treatment to assess its immunomodulatory effects.

Results

Samples from 36 patients completing the study (12 placebo, 24 TPM502) were analyzed across five timepoints. In the placebo group, tet⁺ CD45RA^-CD62L^-CD4⁺ T (Ttet) cells increased after both GCs. By contrast, the TPM502 cohorts exhibited elevated Ttet cell numbers before GC2 (D22) but showed limited expansion afterward (D29), suggesting that TPM502 treatment may prevent further activation-induced expansion. Moreover, the frequency of activated Ttetcells—indicated by activation markers CD38, ICOS, and OX40—significantly decreased across all TPM502 dose levels after GC2 compared to the placebo group (fold change D22 vs D29, all p < 0.0001 by Kruskal-Wallis test). Notably, the diminished gluten response of Ttet cells post-treatment was accompanied by enhanced expression of co-inhibitory receptors TIGIT and PD-1 (D-21 vs D29, p < 0.0001), along with reduced CD127 expression (p < 0.01), indicative of decreased cell survival. These phenotypic changes, consistent with T cell exhaustion or anergy, persisted until study end and were visibly distinct from those in the placebo group, as illustrated by the heatmap of delta log-transformed flow cytometry data of Ttet cells across timepoints, clustered hierarchically. Gliadin-specific CD4⁺ regulatory T cells (CD25⁺CD127^- Ttet) and CD39⁺ Ttet cells increased post-treatment at the highest TPM502 dose, suggesting the induction of regulatory states in these T cells. Moreover, pre-enriched samples showed reduced activation of αEβ7⁺ γδ⁺ and CD8⁺ Tcells after GC2 at the highest TPM502 dose, suggesting potential bystander effects.

Conclusion

Data from the first longitudinal tetramer-based flow cytometry analysis in CeD patients provide evidence that TPM502 induces antigen-specific tolerance through T-cell immunomodulation. These results corroborate other pharmacodynamic outcomes generated in this study, including a significant and dose-dependent reduction in ex vivo IL-2 and IFN-γ secretion by gluten-specific T cells after treatment. In addition to a good safety and tolerability profile of TPM502, this nanoparticle-mediated induction of antigen-specific tolerance may provide a novel therapeutic avenue to treat celiac disease.

Introduction

The phase 2b GALAXI 1 and phase 3 GALAXI 2&3 studies evaluated guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, in participants (pts) with moderately to severely active CD.¹ Pts treated with ustekinumab (UST) who met inadequate response criteria during the long-term extension (LTE) could cross over to GUS 200 mg SC q4w. Here, we present efficacy and safety results in pts who received GUS after experiencing an inadequate response to UST in the pooled GALAXI LTE.

Aims & Methods

Individuals with prior inadequate response or intolerance to UST were excluded from GALAXI; however, during the LTE, pts treated with UST 90 mg SC q8w who met inadequate treatment response criteria (not in clinical response [≥100-point reduction in CDAI score from baseline or CDAI<150] and CDAI ≥220) between Wks 52-80 of LTE were eligible for a treatment switch to GUS 200 mg SC q4w, without IV induction. Clinical response and clinical remission (CDAI<150) were both assessed 16 weeks after treatment switch. Endoscopic response (≥50% improvement from baseline SES-CD or SES-CD≤2) and endoscopic remission (SES-CD≤4 and ≥2-point reduction from baseline and no subscore >1 in any individual component) were assessed at Wk 96. Safety was assessed through Wk 96.

Results

In total, 80 pts treated with UST underwent treatment switch to GUS 200 mg SC q4w maintenance therapy due to meeting inadequate treatment response criteria between Wks 52-80 of the LTE. Of these 80 pts, 75 were included in the efficacy analyses (baseline mean age, 35.2yrs; male, 64.0%; mean CD disease duration, 8.21yrs; mean CDAI, 291.5; mean SES-CD, 12.8; history of inadequate response/intolerance to biologics [BIO-IR], 60.0%).
The proportions of pts achieving clinical response and clinical remission 16 weeks after treatment switch from UST to GUS 200 mg SC q4w were 61.3% and 52.0%, respectively. These results were comparable to the proportions of pts treated with GUS 200 mg IV q4w induction in the BIO-IR subgroup of the total LTE population who achieved clinical response and clinical remission at Wk 12 (61.7% and 46.7%, respectively).
The proportions of pts achieving endoscopic response and endoscopic remission at Wk 96 (ie, ~1 year after treatment switch from UST to GUS 200 mg SC q4w) were 49.3% and 30.7%, respectively. These results were similar to the proportions of pts in the BIO-IR subgroup receiving GUS 200 mg SC q4w maintenance who achieved endoscopic response and endoscopic remission at Wk 48 (57.2% and 35.5%, respectively).
Safety results are summarized in the Table.

Table. Safety Summary From Treatment Switch Through Week 96

Conclusion

Among pts who experienced inadequate response to UST in the LTE, more than half achieved clinical remission 16 weeks after treatment switch to GUS 200 mg SC q4w, and approximately 50% were in endoscopic response ~1 year after treatment switch. These data suggest pts with an inadequate treatment response to UST may benefit from GUS treatment. Results should be interpreted considering that pts received GUS SC maintenance therapy directly without IV induction. Key safety event rates were consistent with the known safety profile of GUS in approved indications.

References

1) Sachen K, Hammaker D, Sarabia I, et al. Frontiers in Immunology. 2025; doi:10.3389/fimmu.2025.1532852.

Disclosure

AA reports potential conflicts of interest with AbbVie, Bristol Myers Squibb/Celgene, DiaSorin, Eli Lilly, Gilead, IBD Horizons, Janssen, Pfizer, Takeda, and TLL Pharmaceuticals
DW reports consulting fees from AbbVie, Bristol Myers Squibb, Janssen, Lilly, Pfizer, Takeda
RL reports having received advisory board fees from AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, and Takeda; received research grants from Celltrion, Shire, Janssen, Takeda, Joanna Tiddy grant from University of Sydney, McCusker Charitable Trust, Gastroenterological Society of Australia, NHMRC, Gutsy Group, and Pfizer
RVR, WvD, and CB are employees of Johnson & Johnson and own company stock/stock options.
TH received grant support from Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co. Ltd., Boston Scientific Corporation, Kissei Pharmaceutical Co. Ltd., consulting fees from Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, Janssen Pharmaceutical K.K., Pfizer Inc., Nichi-Iko Pharmaceutical Co. Ltd., Eli Lilly, Gilead Sciences, Bristol Myers Squibb, and lecture fee from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA pharma Co. Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc. Kissei Pharmaceutical Co. Ltd.
JP reports consultancy fees/honorarium from AbbVie, Alimentiv, Athos, Atomwise, Boehringer Ingelheim, Celsius, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Surrozen, Takeda, and Wasserman, and has served on a data safety monitoring board for Alimentiv, Mirum, Sorriso, Sanofi, and Surrozen.

Introduction

Colorectal cancer (CRC) gradually develops from precancerous lesions - colorectal adenomas or serrated polyps - in the gut. As such, removal of these lesions is an effective prevention of CRC [1]. However, currently currently available non-invasive detection methods – such as the fecal immunochemical test – produce a high number of false positive results, resulting in a high number of unnecessary colonoscopes [1]. CRC has been associated with changes in the gut microbiota, but links between microbiome and pre-cancerous lesions are underexplored and it is unclear if gut microbes can predict the future onset of CRC.

Aims & Methods

We linked the Dutch Microbiome Project - a large-scale prospective population study including 8,208 individuals [3] - with the Dutch nationwide pathology database [4] to identify all recorded cases of colonic biopsies in these individuals from the past five decades. This allowed us to associate gut microbiome to detailed histological information about precancerous lesions and CRC, including when were lesions detected relative to fecal sampling as well as lesion subtype, growth pattern, size, location and the grade of dysplasia. We analyzed the function, composition and metagenome-assembled genome strain profiles of gut microbiota in participants who developed (pre)cancerous colorectal lesions before fecal sampling (n=214, years 2000-2015) and patients developing lesions after fecal sampling (n=305, 2015-2022), using n=202 individuals with normal colonoscopy findings and general population as controls. We associated clinical phenotypes (e.g. type and size of lesion) with microbiome composition and function using multivariate regression and permutational analysis of variance (adonis). Furthermore, we explored strain profiles and functions of associated bacterial species by reconstructing their genomes from metagenomic data using metagenomic assembly and binning approaches.

Results

We found 214 participants with colonoscopy identified precancerous colonic developed before fecal sampling (106 cases of low-grade dysplasia, 24 of high-grade dysplasia, 60 of serrated polyps and 26 cases of CRC), and 305 study participants with lesion developed after the fecal sampling (26 cases of CRC, 149 low grade dysplasias, 78 high-grade dysplasias, 52 serrated polyps and 26 cases of CRC). Microbiome diversity was decreased in participants who developed colonic lesions after sampling (FDR < 0.05) and microbiome composition and function were different in patients with pre-existing or future lesions as well as with types of lesions (CRC, high-grade dysplasia, low-grade dysplasia or serrated polyp; adonis FDR < 0.05). Bacterial species from family of Lachnospiraceae, and the genera Roseburia and Eubacterium were linked with future development of lesions, while associated functions involved methanogenesis, biosynthesis of aerobactin, queuosine and flavine and degradation of lysine. Microbiome composition had a moderate predictive power for future lesions and CRC (AUROC ~0.7).

Conclusion

We found that the gut microbiome of study participants who developed (pre)cancerous colonic lesions in 2015-2022 is significantly different from general population, implying that the gut microbiota might be involved in the development of colorectal lesions and cancer. Our results suggest that the gut bacteria might be used to enhance currently used diagnostics for detection of colorectal polyps and that microbiome-modulating therapies might play a role in prevention of colorectal cancer.

References

[1] Integraal kankercentrum Nederland (IKNL) & National Institute for Public Health and the Environment (RIVM): National monitoring of colorectal cancer screening in the Netherlands (2019)
[2] Yachida, S. et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nature Medicine. 25, 968–976 (2019)
[3] Gacesa, R. et al. Environmental factors shaping the gut microbiome in a Dutch population. Nature. 604, 732–739 (2022)
[4] Casparie, M. et al. Pathology databanking and biobanking in The Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive. Anal Cell Pathol. 29 (1), 19-24 (2007)

Disclosure

RKW received unrestricted grants from Takeda, Johnson and Johnson, Tramedico, Ferring, and acted as consultant for Takeda. GAPH acted as consultant for Amgen, Bristol-Myers Squibb, Roche, MSD, Pfizer, Novartis, Sanofi, and Pierre Fabre.

Introduction

Guselkumab (GUS), a dual-acting interleukin-23p19 subunit inhibitor, demonstrated efficacy in participants (pts) with ulcerative colitis (UC) treated with intravenous (IV) or subcutaneous (SC) induction. Here, we report the efficacy and safety of SC induction followed by SC maintenance through Week (W) 48 in ASTRO, a phase 3, randomized, double-blind, placebo (PBO)-controlled, treat-through study in pts with moderately to severely active UC.

Aims & Methods

Eligible pts had modified Mayo scores of 5 to 9, rectal bleeding subscore of ≥1, and Mayo endoscopic subscore (MES) ≥2. Pts also had documented inadequate response/intolerance to biologics, Janus kinase (JAK) inhibitors, and/or sphingosine-1-phosphate (S1P) inhibitors (BIO/JAKi/S1Pi-IR) or to corticosteroids, 6-mercaptopurine, or azathioprine. Randomization was stratified by baseline BIO/JAKi/S1Pi-IR status and MES with 418 pts allocated 1:1:1 to GUS 400 mg SC every 4 weeks (q4w) (×3)→GUS 200 mg SC q4w (N=140), GUS 400 mg SC q4w (×3)→GUS 100 mg SC every 8 weeks (q8w) (N=139), or PBO SC (N=139). PBO pts who met rescue criteria were switched to GUS at W16; GUS pts who met rescue criteria stayed on their assigned GUS dose regimen (sham rescue).

Results

At W48, greater proportions of pts in the GUS groups achieved clinical remission compared with PBO (36.7% for GUS 100 mg q8w [Δ 29.5%], 42.9% for GUS 200 mg q4w [Δ 35.6%], 7.2% for PBO) (Table). Endoscopic remission proportions were 25.9% for GUS 100 mg q8w (Δ 20.9%), 26.4% for GUS 200 mg q4w (Δ 21.4%), and 5.0% for PBO. Clinical response, symptomatic remission, endoscopic improvement, histologic improvement, and histologic remission proportions were also greater for GUS vs PBO. Consistent with the results of the overall population, efficacy was also observed for subpopulations of BIO/JAKi/S1Pi-naïve and BIO/JAKi/S1Pi-IR pts. Safety events per 100 pts-years were not greater in the GUS groups compared with the PBO group: adverse events (AE) (GUS 100 mg q8w and 200 mg q4w vs PBO: 308.3 and 310.7 vs 357.1), serious AEs (6.5 and 8.2 vs 38.4), serious infections (0.8 and 2.5 vs 3.7), and AEs leading to treatment discontinuation (4.9 and 4.1 vs 19.8).
Table. Efficacy endpoints at Week 48 in the overall population and by biologic, JAK inhibitor, and/or S1P inhibitor history

Conclusion

GUS SC induction followed by SC maintenance was efficacious through 1 year in pts with moderately to severely active UC, and the safety profile is consistent with GUS in its approved indications including UC.

Disclosure

ML reports research support from Lilly, Pfizer, and Takeda; consulting for AbbVie, Bristol Myers Squibb, Intercept, Janssen (Johnson & Johnson), Lilly, Pfizer, Prometheus, Roivant, Takeda, and Target RWE.
JRA reports grant support from Janssen, Merck, and Pfizer; consultancy fees from AbbVie, Adiso, Bristol Myers Squibb, Ferring, Genentech, GlaxoSmithKline, Janssen, Merck, Pfizer, Roivant, Celltrion, TrexBio, Shattuck Labs and Seres Therapeutics; payments for speaking from AbbVie, Bristol Myers Squibb, and Janssen; and is a steering committee member and investigator for Janssen.
SD reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB, and Vifor; and reports lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, and Takeda.
MG, TB, YA, KH, SJ, LJ, and HZ are employees of and may own stock in Johnson & Johnson.
TH reports research grants from AbbVie GK, Boston Scientific Corporation, EA Pharma Co. Ltd., JIMRO Co. Ltd., Kissei Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Pfizer Inc., Takeda Pharmaceutical Co. Ltd., and Zeria Pharmaceutical Co. Ltd.; consulting fees from AbbVie GK, Abivax, Bristol Myers Squibb, EA Pharma Co. Ltd., Gilead Sciences, Janssen Pharmaceutical K.K., Lilly, Mitsubishi Tanabe Pharma Corporation, and Pfizer Inc.; and lecture fees from AbbVie GK, EA Pharma Co. Ltd., Janssen Pharmaceutical K.K., JIMRO Co., Kissei Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co. Ltd.
DTR reports consulting and/or speaker fees and/or advisory board participation for AbbVie, Altrubio, Apex, Avalo, Bristol Myers Squibb, Buhlmann Diagnostics, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Janssen (Johnson & Johnson), Lilly, Pfizer, Samsung Neurologica, and Takeda; Altrubio, Datos Health, and Iterative Health stock options; grants from Takeda; and membership on the Board of Directors of Cornerstones Health, Inc. and on the Crohn’s & Colitis Foundation’s Board of Trustees.
LPB reports grants or contracts from Celltrion, Fresenius Kabi, Medac, MSD, and Takeda; consulting and/or payment or honoraria and/or data safety monitoring board or advisory board participation for AbbVie, Abivax, Adacyte, Alfasigma, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, Bristol Myers Squibb, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GlaxoSmithKline, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Kern Pharma, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par' Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx, and Ysopia; and meeting attendance/travel support from AbbVie, Alfasigma, Amgen, Celltrion, Connect Biopharm, Ferring, Galapagos, Genentech, Gilead, Gossamer Bio, Janssen, Lilly, Medac, Morphic, MSD, Pfizer, Sandoz, Takeda, Thermo Fischer, and Tillots.

Introduction

Fistulizing perianal Crohn’s disease (CD) remains a significant therapeutic challenge, with limited randomized controlled trials to date, restricted so far to infliximab and, more recently, filgotinib. The USTAP (NCT04496063) trial aimed to evaluate the efficacy and safety of UST in patients with actively draining perianal fistulas through a multicenter randomized controlled design.

Aims & Methods

This double-blind, placebo-controlled, multicenter trial enrolled adult patients with active draining fistulizing perianal CD. Between April 2020 and June 2024, eligible patients with persistent fistula drainage were randomized 1:1, after seton placement when necessary, to receive either UST (6 mg/kg IV at baseline followed by 90 mg SC at week 8, then every 8 weeks) or placebo. Steroids were allowed at baseline with a standardized steroid taper. Seton removal was planned at week 6. The primary endpoint was combined clinical remission (absence of drainage from all external fistula openings) and radiological remission (defined as the absence of abscesses >2 cm confirmed by blinded central pelvic MRI) at week 12. Secondary endpoints included clinical remission, radiological remission, changes in disease activity (CDAI, PDAI), IBD-DI, and safety. Endpoints were independently reviewed by a blinded adjudication committee. Randomization was stratified by prior anti-TNF exposure and study center. The intended sample size was 73 patients per group to detect a 20% difference in remission rates (power 80%, alpha 5%). Due to slow recruitment, the study was discontinued in June 2024 after randomizing 32 patients, without unblinding the study data. Patients were subsequently followed until week 48.

Results

Thirty-three patients consented to participate with 32 patients (women: 41%; median age: 42) ultimately randomized (UST: 16; placebo: 16) across 10 French centers. Seventy percent had prior anti-TNF exposure (50% in UST arm, 50% in placebo arm), and 23% had previously failed two or more anti-TNF therapies. At baseline, 84% had one draining fistula, 16% had two, and 25% had associated abscesses. At week 12, combined remission was achieved in 62% in the UST group versus 25% in the placebo group (Table). Clinical remission was observed in 69% in the UST group vs. 31% in the placebo group, while radiological remission rates were 87.5% in the UST group and 75% in the placebo group. In the UST arm, mean change in CDAI, PDAI and IBD-DI from baseline to week 12 was -56.3, -2.2 and -4.9, (vs. -9.8, -1.6 and +4.9, in the placebo arm, respectively). Adverse events (AE) and serious adverse events (SAE) were similar in both treatment groups: 23 AE (62%) occurred in the placebo group, and 14 AE (38%) in the UST group. Six SAEs were reported overall, including two gastrointestinal events, one renal disorder, and one anal abscess. Two patients in the placebo group discontinued study by week 6 due to SAEs (an anal abscess and a peri-ileal abscess).

Conclusion

In this trial, where the majority of patients had prior anti-TNF exposure, the observed short-term clinical benefit of UST supports its use in fistulizing perianal CD.

Disclosure

This work was supported by a grant from Johnson & Johnson
Pauline Wils : Johnson & johnson, Takeda, Amgen, Abbvie, Celltrion, Ferring
S Nancey: Abbvie, Johnson and Johnson, Fresenius Kabi, Biogen, Takeda, Medac, Celltrion, MSD, Pfizer, Sandoz, Lilly,Ferring, Amgen
E. Messmer: No conflict of interest for this study
A Bourreille: Johnson and Johnson
A Buisson: Consulting fees from: Abbvie, Amgen, Arena, Biocon, Biogen, Celltrion Healthcare, CTMA, Ferring, Galapagos/AlfaSigma, GutyCare/Resilience Janssen, Lilly, MSD, Nexbiome, Pileje, Pfizer, Roche, Sandoz, Takeda et Tillotts. Lecture fees from: Abbvie, Amgen, Biogen, Celltrion Healthcare Galapagos/AlfaSigma, Ferring, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Norgine, Pfizer, Roche, Takeda, Tillotts and Vifor Pharma. Research grants/fundings from: Abbvie, Celltrion Healthcare, Janssen, Lessaffre, Lilly, Pfizer, Sandoz and Takeda
L Caillo: No conflict of interest for this study
L Vuitton: abbvie amgen J&J Pfizer Takeda Lilly MSD Mayoli Ferring Dr Falk Alpha Sigma
R Altwegg: Abbvie, Johnson ans Johnson, Takeda, Pfizer, Lilly, Alphasigma, Celltrion, Amgen, Biogen, Sandoz, Ferring
X Hébuterne reports clinical research funding from Abbvie, Abivax, Amgen, Celltrion, Lilly, Fresenius-Kabi, J&J, InDex Pharmaceuticals, Pfizer, Prometheus, MSD, Roche, Takeda, serving on advisory boards for Abbvie, Biogen, Celltrion, Lilly, J&J, and participating in lectures and educational activities for Abbvie, Amgen, Celltrion, Lilly, Fresenius-Kabi, Galapagos, J&J, MSD, Nestlé Health Sciences, Nutricia, Pfizer, Tillots, Takeda.
O Ernst: No conflict of interest for this study
P Meunier: No conflict of interest for this study
V Laurent: No conflict of interest for this study
D Laharie: received board and lecture fees from: Abbvie, Alfasigma, Amgen, Biogen, Celltrion, Ferring, Fresenius-Kabi, Janssen, Lilly, MSD, Pfizer, Roche, Sandoz, Takeda
E Vicaut: No conflict of interest for this study
L Peyrin-Biroulet: Consulting : Abbvie, Abivax, Adacyte, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, BMS, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par' Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx, Ysopia ; lecture : Abbvie, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots, Viatris