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

Immune checkpoint inhibitors (ICIs), a new class of immunotherapeutic agents, are the first-line treatment for many advanced epithelial cancers. Gastrointestinal irAEs, particularly diarrhea and colitis, affect approximately 40% of ICI-treated patients and often lead to therapy discontinuation.¹ High-dose corticosteroids represent the first-line treatment, but about one-third of patients show inadequate response and require second-line immunosuppressants such as Infliximab or Vedolizumab.² As the body of evidence about the role of gut microbiota in the pathogenesis of GI irAE grows, fecal microbiota transplantation (FMT) is emerging as a potential treatment for steroid- and biologic-refractory ICI-induced colitis.³ Although data are still preliminary, FMT represents a promising therapeutic strategy in this setting.

Aims & Methods

The aim of this study is to evaluate the safety and efficacy of FMT in patients referred to our Microbiome clinic for steroid- and biologic-refractory ICI-induced colitis. After clinical evaluation, patients were treated with FMT via colonoscopy from healthy donors. FMT was performed as already described, following international clinical guidelines.^4,5 Following the endoscopic procedure, patients were evaluated at 1, 4, 8, and 12 weeks. We collected data on: patient characteristics, cancer type, cancer treatment and its suspension, severity of diarrhea before FMT (graded via CTCAE)⁶, time in weeks from initiation of cancer therapy to onset of diarrhea, grade of diarrhea following treatment and resumption of ICI.

Results

Our cohort included 7 patients with steroid- and biologic-refractory ICI-induced colitis (grade 1: n=0 ; grade 2: n=1 ; grade 3: 5=x; grade 4: n=1). Four patients were affected by renal cell carcinoma, 2 by melanoma, 1 by pulmonary cancer. All patients were treated with PD-1/PDL-1 inhibitors or CTLA-4 ( Nivolumab: n= 3; Nivolumab and Ipilimumab: n=2; Durvalumab: n= 1; Pembrolizumab: n= 1) and 6 patients interrupted ICI due to gastrointestinal irAEs. All patients received single FMT from healthy donors via colonoscopy. Following FMT, diarrhea improved to grade ≤ 1 in 6 patients (85%) at week 1, 4, 8, and 12 after the procedure, suggesting a sustained effect of microbiome modulation in the medium term. One patient died during follow-up for reasons other than ICI-colitis.

Conclusion

Our preliminary findings suggest that FMT may be a promising therapeutic strategy for refractory ICI-colitis. Further, larger and randomized studies are warranted to confirm our data.

References

1. Dougan M, Wang Y, Rubio-Tapia A, Lim JK. AGA Clinical Practice Update on Diagnosis and Management of Immune Checkpoint Inhibitor Colitis and Hepatitis: Expert Review. Gastroenterology. 2021;160(4):1384-1393. doi:10.1053/j.gastro.2020.08.063
2. Haanen J, Obeid M, Spain L, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(12):1217-1238. doi:10.1016/j.annonc.2022.10.001
3. Wang Y, Wiesnoski DH, Helmink BA, et al. Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis. Nat Med. 2018;24(12):1804-1808. doi:10.1038/s41591-018-0238-9
4. Cammarota G, Ianiro G, Kelly CR, et al. International consensus conference on stool banking for faecal microbiota transplantation in clinical practice. Gut. 2019;68(12):2111-2121. doi:10.1136/gutjnl-2019-319548
5. Ianiro G, Rossi E, Thomas AM, et al. Faecal microbiota transplantation for the treatment of diarrhoea induced by tyrosine-kinase inhibitors in patients with metastatic renal cell carcinoma. Nat Commun. 2020;11(1):4333. doi:10.1038/s41467-020-18127-y
6. Freites-Martinez A, Santana N, Arias-Santiago S, Viera A. Using the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0) to Evaluate the Severity of Adverse Events of Anticancer Therapies. Actas Dermosifiliogr. 2021;112(1):90-92. doi:10.1016/j.ad.2019.05.009

Disclosure

G.I. has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics and Tillotts Pharma, and for acting as consultant and/or advisor for Ferring Therapeutics, Giuliani, Malesci and Tillotts Pharma. A.G. reports personal fees for consultancy from Eisai Srl, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, SinergieSrl, Board MRGE and Sanofi SpA personal fees for acting as a speaker for Takeda SpA, AbbVie and Sandoz SpA and personal fees for acting on advisory boards for VSL3 and Eisai. G.C. has received personal fees for acting as advisor for Ferring Therapeutics. All other authors have no conflicts of interest to disclose.

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. In the QUASAR studies, GUS intravenous (IV) induction and subcutaneous (SC) maintenance demonstrated symptomatic, endoscopic, and histologic efficacy through 2 years.^1,2 Here, we describe maintenance of endoscopic and histologic efficacy in the long-term extension (LTE).

Aims & Methods

At maintenance week (W) 0, GUS IV induction responders were randomized 1:1:1 to GUS 100 mg SC every 8 weeks (q8w), GUS 200 mg SC q4w or placebo (GUS withdrawal). Participants (pts) completing the W44 visit could enter the LTE and continue the treatment regimen they were receiving at W44. Placebo pts discontinued after study unblinding. Efficacy data for randomized pts who continued to receive their GUS regimen assigned at W0 in the LTE were analyzed using 2 methods: 1) nonresponder imputation (NRI) accounting for pts with treatment failure or missing data, and 2) “as observed.”

Results

Overall, 303 randomized pts (155 for 100 mg q8w and 148 for 200 mg q4w) continued their GUS treatment assigned at W0 in the LTE. Of pts who achieved endoscopic improvement at W44, 87.2% of GUS 100 mg q8w pts and 80.2% GUS 200 mg q4w pts maintained endoscopic improvement through W92 (NRI analysis; Table). Of pts who achieved histologic improvement at W44, 77.9% and 75.2%, respectively, maintained histologic improvement at W92. Of pts who achieved histo-endoscopic mucosal improvement (HEMI) at W44, 73.5% and 75.5%, respectively, maintained HEMI through W92. Of pts who were in histologic remission at W44, 71.2% maintained histologic remission at W92 in both GUS groups. Results of the as-observed analysis were consistent with the NRI analysis; the dropout rate was low among GUS-treated pts in the LTE. Proportions of pts who maintained endoscopic and histologic outcomes from W0 to W92 are presented in the Table.

Conclusion

High rates of long-term sustained endoscopic and histologic endpoints were observed at W92 of the LTE with both GUS dose regimens.

References

1. 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.
2. Lichtenstein GR, et al. Efficacy and safety of guselkumab for ulcerative colitis through week 92 of the QUASAR long-term extension study. Presented at: Digestive Disease Week (DDW); May 4–6, 2025; San Diego, CA.

Disclosure

Study support: Johnson & Johnson.
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, Takeda Pharmaceutical Co., Ltd.
JP: AbbVie, Alimentiv, Athos, Atomwise, Boehringer Ingelheim, Celsius, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Johnson & Johnson, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Surrozen, Takeda, Wasserman.
FM: AbbVie, Arena, Celltrion, Eli Lilly and Company, Ferring, Fresenius, Galapagos, GlaxoSmithKline, Johnson & Johnson, Merck, Pfizer, Prometheus Biosciences, Roche, Sandoz, Tillots, Takeda, Teva.
GRL: AbbVie, American College of Gastroenterology, CellCeutrix, Celgene, Clinical Advances in Gastroenterology, Ferring, Gastroenterology and Hepatology [Gastro-Hep Communications], Gilead, Johnson & Johnson, Orthobiotech, Eli Lilly, Luitpold / American Regent, Merck, McMahon Publishing, Pfizer, Prometheus, Romark, Salix/ Valeant, Shire, SLACK, Springer, Takeda, UCB, Up-To-Date, Vindico, Virgo.
JRA: Abbvie, Bristol Myer Squibb, Ferring, Finch, Iterative Scopes, Johnson & Johnson, Merck, Pfizer, Roivant, Seres Therapeutics, Roivant Adiso.
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, Viatris.
WA: AbbVie, Amgen, BMS, Dynacare, Eli-Lilly, Johnson & Johnson, Merck, Novartis, Pfizer, Prometheus, Sandoz, Sanofi, Takeda, Theradiag.
MAS: AbbVie, Bristol-Myers Squibb, Falk, Galapagos, Janssen, Lilly, MSD, Pfizer, Samsung Bioepis, Sandoz, Sanofi, STADA, Takeda, Tillotts.
BDY: AbbVie Korea, BMS Pharmaceutical Korea Ltd., Celltrion, Chong Kun Dang Pharm, CJ Red BIO, Cornerstones Health, Curacle, Daewoong Pharm, Dong-A ST, Eisai Korea, Eli Lilly and Company Korea, Ferring Korea, Imscout, IQVIA, Johnson & Johnson, Johnson & Johnson Korea, JEIL PHARMACEUTICAL CO., Kangstem Biotech, Korea Otsuka Pharm, Korea United Pharm, Medtronic Korea, NanoEntek, ORGANOIDSCIENCES LTD, Pfizer Korea, Samsung Bioepis, Takeda, Takeda Korea, Yuhan.
SY, MG, NS, DP, YM, HZ: Johnson & Johnson.
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, Vifor Pharma.
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, Takeda.
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.

Introduction

Crohn's disease (CD) is a disabling and destructive disease. Early intervention associated with tight monitoring appear to the best way to achieve deep remission and to prevent disease progression. Whether anti-TNF (tumor necrosis factor) therapy can be interrupted in patients with early CD who have undergone a period of prolonged deep remission is unknown.

Aims & Methods

The primary objective was to evaluate the sustained deep remission rate one year after discontinuation of a 12-month course of adalimumab in adult patients with early CD who achieved deep remission at 12 months after treatment induction and who were already in clinical remission and biomarker remission at 6 months.
We carried out a multicentre prospective GETAID cohort study. All patients had early luminal CD less than 24 months since diagnosis, and were naïve to biologics. The primary study endpoint was percentage of patients with sustained deep remission one year after stopping a 12-months course of adalimumab (+/- 3 months) in adult patients with early-stage CD who achieved deep remission without therapeutic intervention (i.e. no surgery, no clinical flare-up, no introduction of CD-related treatment, no need for adalimumab optimization) AND who were already in clinical remission (CDAI < 150) and biomarker remission (CRP < 5 mg/L and fecal calprotectin < 250) at 6 months. A clinical flare-up was defined as a CDAI > 220 or an increase in CDAI between two subsequent visits > 70.

Results

A total of 171 patients received treatment with adalimumab between March 2015 and March 2019.
In this cohort, 39.2% (67/171) were active smokers. The median disease duration was 4 [2-9] months. CD location was ileal (42.7%, 73/171), colonic (12.3%, 21/171), and ileo colonic (44.4%, 76/171). Twenty-one patients (12.3%) had perianal disease. The majority of patients had an inflammatory phenotype (71.3%, 122/171). At inclusion, median CRP level was 9.0 [3.0-24.0] mg/L, and median fecal calprotectin was 440.5 [159.0-838.0] µg/g.
Overall, 38/171 (22.2%) of patients achieved deep remission after a 12-month course of adalimumab. From those who achieved deep remission, 7 patients did not discontinue adalimumab. In this study, 7/31 (22.6%) patients maintained their deep remission for one year after their treatment discontinuation (24 months from initiation of adalimumab). Among the whole cohort, only 4% (7/171) of patients were in deep remission off adalimumab at 2 years. Median time between adalimumab discontinuation and the first clinical relapse was 14 months. No predictive factor associated with loss of deep remission in the year following treatment discontinuation was identified. No serious adverse event was reported.

Conclusion

In this first prospective trial exploring withdrawal of advanced therapy in early CD, 22.6% achieved deep remission at one year with adalimumab; among them, about a quarter maintained deep remission at two years. These results demonstrate that anti-TNF therapy should not be discontinued, even in patients with early CD.