Introduction

Many prospective studies conducted in healthy volunteers have shown that diet is associated with the risk of developing IBD. By contrast, data are scarce on the role of diet in disease activity in patients with IBD. The aim of the present study was to find dietary factors associated with the risk of IBD relapses.

Aims & Methods

The “Mikinautes” e-cohort is a nationwide French prospective study recruiting IBD patients older than 6 years at inclusion and followed in private practice and public hospitals. French Crohn and Colitis Patients’ association was also involved in the design, funding and recruitment. Patients filled in online questionnaires about their dietary habits and health status. Validated food frequency questionnaires (FFQ) recorded average intakes of 230 food items over the past 12 months. Patients were followed for at least one year and medical records were prospectively collected. Relapse was defined by i) an increased disease activity reported monthly by the patients and/or a clinical report mentioning a relapse, together with ii) a documented consultation with a doctor and iii) a change in IBD therapy, either drug, enteral nutrition and/or surgery).
A posteriori dietary patterns (DPs) were identified using principal component analysis (PCA) performed on 31 food groups. Primary analysis was a Cox model among patients in remission at inclusion to reduce potential reverse causality. Secondary analyses included: i) a Cox model conducted among all patients, which measured the time between the onset of the last relapse before inclusion (or the ongoing relapse at inclusion) and the first relapse during follow-up and ii) a logistic model comparing inactive versus active patients (defined as patients who had at least one relapse at inclusion or over the first year of follow-up). Models were adjusted for age, sex, smoking status and energy intake.

Results

After exclusion of 14 patients with implausible dietary intakes, 693 patients were retained for analyses, comprising 66% of females, 59% Crohn Disease (CD) patients, 34% ulcerative colitis (UC) patients and 7% indeterminate colitis (IC). Median follow-up [Q1-Q3] was 2.1 years [1.6;2.7]. 77% of patients were in remission at inclusion. Their cumulative probability (95% CI) of flare were 18% [15%; 21%] at 1 year and 25% [22%; 29%] at 2 years. In total, 36% of patients had an active disease after one year of follow-up (including active patients at inclusion).
Four DPs were identified through PCA. In CD, primary Cox analysis revealed an association between the second DP and disease activity (HR 95% CI: 0.42 [0.22;0.80] for 3^rdvs 1^st tertile of consumption, p-trend=0.050). This DP was characterized by high intakes of vegetables, fruit, nuts, legumes, cereals, eggs and unsweetened beverages and by a low consumption of dairy products and desserts, bread, sweet/fat or salty/fat products. Secondary analyses confirmed this association (HR: 0.37 [0.18;0.78] for 3^rdvs 1^st tertile, p-trend=0.010; OR: 0.42 [0.22;0.80] for 3^rdvs 1^st tertile, p-trend=0.010). In UC, fruit consumption was protective toward relapse in primary (HR: 0.46 [0.26;0.82] for 3^rdvs 1^st tertile, p-trend=0.009) together with secondary analyses; no dietary pattern was associated with relapse.

Conclusion

A diet characterized by a high consumption of fruit, vegetables, legumes and nuts is associated with a reduction in the risk of relapse by half in patients with CD. High fruit consumption is associated with the same decreased risk of relapse in patients with UC. These results inform dietary counseling in IBD.

References

Acknowledgements: This study was funded by the French association AFA Crohn-RCH France. It was supported by the networks of the Pediatric GETAID, the GETAID, the CREGG, the ANGH and EPIMAD. We thank Nutrinet-Santé, IBD patients and their doctors who contributed to this study.

Disclosure

FC reports receiving research grants from Alpha Wassermann, MaaT pharma, Mayoly Spindler, Medtronic, Nestlé; receiving payment for lectures from AbbVie, AlphaSigma, Ferring, Janssen, Eli Lilly,
Nestlé Health Sciences, Pierre Fabre, Pileje, Takeda, Tillots, Viatris ; receiving consulting fees from AbbVie, Janssen, MaaT pharma, Tillots. HS, SA, CGR, AB, LD and JPH have nothing to declare.

Introduction

​​​​​Guselkumab (GUS) is a selective dual-acting IL-23p19 subunit inhibitor that potently blocks interleukin 23 (IL-23) and binds to CD64, a receptor on cells that produce IL-23¹. In patients with moderately to severely active Crohn’s disease (CD), the GALAXI-2 and GALAXI-3 Phase 3 studies established short- and long-term efficacy of GUS compared to placebo, and statistical superiority to ustekinumab (UST) in prespecified analyses of pooled data at Week (WK)48². We subsequently developed an endoscopic clustering method using Simple Endoscopic Score for Crohn's Disease (SES-CD) segmental scores in patients from GALAXI 2/3 which revealed higher endoscopic remission rates with GUS compared with UST at WK12 and WK48 in pts characterized by ileal disease and strictured right colon³. Here we report molecular differentiation of GUS compared with UST in isolated ileal disease based on serum pharmacodynamic (PD) markers and tissue transcriptomics in CD using pooled samples from the GALAXI studies.

Aims & Methods

Patients (pts) in GALAXI-2 (n=508) and GALAXI-3 (n=513) were randomized 2:2:2:1 to receive GUS 200mg IV q4w x3 → GUS 200mg SC q4w, GUS 200mg IV q4w x3→ GUS 100mg SC q8w, UST ⁓6mg/kg IV x1 → UST 90mg SC q8w or placebo IV q4w x3 (PBO). Serum biomarkers were measured in a subset of (n=50) pts per group at WK0, WK4 and WK12 using a proinflammatory panel and a high sensitivity IL-22 assay. Matched ileal and rectal biopsies were evaluated at WK0, WK12 and WK48 in a subset of 344 pts representative of the full study population. Transcriptional profiling was performed with bulk RNA sequencing (RNAseq) using transcriptional modules. Analysis of treatment effects was performed using molecularly inflamed samples (biopsy molecular inflammation score [bMIS]⁴ >0) from segments with SES-CD >0 at baseline. Serum proteins and transcriptional modules were evaluated for differential expression stratified by isolated ileal, isolated colonic and ileocolonic disease defined during screening.

Results

In pts with isolated ileal disease, GUS decreased serum protein levels of IL-22, IL-17A and IFNγ at WK12 while UST only reduced IFNγ. In ileal tissue, GUS significantly altered inflammatory modules at WK12 and WK48 including reductions in neutrophil, inflamed epithelium, IL-23/Th17 and inflammatory fibroblast biology compared with minimal changes observed with UST, which only significantly reduced neutrophil, plasma cell and macrophage modules at WK48. In contrast, in pts with isolated colonic or ileocolonic disease, both GUS and UST decreased IL-23-dependent serum proteins towards normal levels compared with an independent cohort of healthy control sera. In rectal tissue, both GUS and UST significantly altered key inflammatory transcriptional modules in rectal biopsies at WK12 and WK48. Overall, greater effects of GUS vs UST were observed in ileal tissue at WK12 and at WK48 in transcriptional modules associated with decreasing disease-related features and restoring epithelial health than UST.

Conclusion

GUS decreased IL-23-dependent serum proteins and improved tissue transcriptional profiles in pts with isolated ileal disease while UST only reduced serum IFNγ and had a minimal impact on IL-23-dependent transcriptional modules. These data suggest potential differences in IL-23 and IL-12 pathway enrichment in isolated ileal disease where inhibition of IL-23p19 subunit with GUS achieved greater molecular treatment effects early which were maintained through WK48 and associated with differential clinical outcomes in patients with isolated ileal disease.

References

1. Sachen K, Hammaker D, Sarabia I, et al. Guselkumab binding to CD64+ IL-23–producing myeloid cells enhances potency for neutralizing IL-23 signaling. Frontiers in Immunology. 2025; doi:10.3389/fimmu.2025.1532852
2. Panaccione R, Danese S, Feagan BE, et al. Efficacy and safety of guselkumab therapy in patients with moderately to severely active Crohn’s disease: results of the GALAXI 2 & 3 phase 3 studies. Gastroenterology. 2024; 5 (Supplement): p1057b
3. Richards D, Seridi L, Sohn, K, et al. Guselkumab shows higher endoscopic remission rates than ustekinumab in patients characterized by isolated ileal and srtictured right colon Crohn’s disease: Post-hos analysis of GALAXI 2/3 Ph3 trials. DDW 2025 Abs #4253526; poster.
4. Argmann C, Hou R, Ungaro, R, et al. A biopsy and blood-based molecular biomarker of inflammation in inflammatory bowel disease. Gut. 2022; 0:1-17.

Disclosure

DR, KS, MZ, RP, BM, NAT, MV, DC and PB are current or former employees of Janssen and may hold stock in Johnson & Johnson.
WR has served as a speaker for AbbVie, Celltrion, Ferring, Janssen, Galapagos Medice, MSD, Roche, Pfizer, Sobi, Takeda, as a consultant for AbbVie, Amgen, AOP Orphan, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celltrion, Eli Lilly, Galapagos, Gilead, Index Pharma, Janssen, Medahead, Microbiotica, Pfizer, Takeda; as an advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Galapagos, Janssen, Pfizer, and has received research funding from AbbVie, Janssen, Sandoz, Sanofi, Takeda.

Introduction

Response to hepatitis B vaccine (HBV) is variable in inflammatory bowel disease (IBD) patients with seroconversion rates of 34-89%. Strategies suggested to improve the seroconversion rates are double dose, accelerated schedule, or addition of booster dose with variable results. This study compared the standard (20 µg) dose and double (40 µg) dose of HBV vaccination in IBD patients.

Aims & Methods

Patients of IBD were randomized to 1:1 to receive standard or double dose of HBV at 0, 1 and 6 months. Anti-HBs titers were assessed at 1 month after the third dose. Response was defined as an adequate immune response (AIR, anti-HBs titer >10 mIU/mL) and effective immune response (EIR, anti-HBs titer >100 mIU/mL). Total mayo score and Crohn’s disease activity index (CDAI) was used to identify the active disease. IBD medications with immunosuppressive effects were categorized as immunomodulators, corticosteroids, tofacitinib and biologic group. Multivariable logistic regression analysis was done to identify the predictors of AIR and EIR.

Results

Eighty-eight patients of IBD were randomized to receive standard (45, 51.1%) or double (43, 48.9%) dose of HBV. 79 of 88 patients had ulcerative colitis (UC) and 9 had Crohn’s disease (CD). 49 (55.7%) patients had active disease while 39 (44.3%) were in remission. At the end of the study, total 63 (71.61%) patients achieved AIR and 51 (60%) achieved EIR. AIR (88.4 % vs. 55.6 %, p 0.001) and EIR (69.8% vs. 46.7%, p = 0.028) rates were significantly higher with double dose compared to standard dose of HBV. Patients with active IBD had higher AIR (87.5% vs. 44%, p = 0.001) and EIR (70.8% vs. 32%, p = 0.007) rates with double dose of HBV. Patients with IBD in remission also had higher AIR (89.5% vs. 70%) and EIR (78.4% vs. 65%) rates with double dose of HBV, though statistically non-significant.
Multivariable analysis identified the use of double dose of HBV {odds ratio (OR) 10.865, 95% confidence interval (CI): 2.418-48.817} and biologic (OR 0.022, 95% CI: 0.001-0.421) as predictors to achieve AIR. Similarly, double dose of HBV (OR 3.0, 95% CI: 1.087-8.280) and use of biologic (OR 0.074, 95% CI: 0.006-0.931) also predicted the EIR.

Conclusion

Double dose of HBV vaccine demonstrated a superiority over standard dose of vaccine for achieving both AIR and EIR. Use of biologic impaired the response. Double dose of HBV should be used in IBD patients to improve the seroconversion rates.

Disclosure

No conflict of Interest