Introduction

Management of perianal fistulas in Crohn’s disease (CD) is challenging and requires a multidisciplinary approach, combining surgical drainage and biologic therapies, such as infliximab (IFX). Higher IFX trough concentrations have been associated with improved fistula healing rates. The subcutaneous (SC) formulation of IFX achieves 2–3 times higher and more stable trough levels compared to intravenous (IV) formulation. This study hypothesizes that SC IFX could enhance perianal fistula healing rates in CD patients.

Aims & Methods

REMSILAP study is part of the 3TLAP cohort, a French prospective multicenter observational study evaluating optimal therapeutic strategies for achieving clinical and radiological remission of perianal fistulas in CD at 12 months post-surgical drainage. The REMSILAP substudy focuses specifically on patients receiving SC IFX. Patients who received SC IFX after or within six months prior to surgical drainage were included. Baseline was defined as the day of surgical drainage. The primary outcome was the proportion of patients achieving complete clinical remission defined as Perianal Disease Activity Index (PDAI) fistula drainage subscore = 0 associated with PDAI activity restriction subscore <3 and absence of seton, and radiological remission at 12 months. Here, we present preliminary findings from REMSILAP.

Results

Among the 353 patients enrolled in the 3TLAP cohort, 54 were included in REMSILAP. The cohort consisted of 61.1% male patients, with a median age of 36 years and a median disease duration of 4.5 years. Penetrating disease (B3 phenotype) was present in 40.7%, and 33.3% had a history of surgical resection. At baseline, 40.7% of patients had quiescent disease regarding Harvey-Bradshaw index, while 5.6% had severe disease activity. Biologic exposure prior to inclusion was noted in 42.6%. Surgical drainage, with seton placement, was performed in 74.1% of patients. Forty-eight patients (88%) initiated SC IFX treatment after surgical drainage. Of the patients receiving SC IFX, 50% transitioned to SC IFX after less than three IV infusions. Among those on IV IFX at baseline, 20.4% were receiving a 10 mg/kg dose. Forty-three patients (79.6%) received SC IFX in combination with immunomodulators (azathioprine, methotrexate, or 6-mercaptopurine). The median duration of SC IFX treatment was 13.1 months, with treatment maintained for 67.5% of the follow-up period (mean: 19.3 ± 11.3 months). Forty-three patients (79.6%) were treated with a stable dose of 120 mg/14 days and 6 patients (11.1%) had an intensification of SC IFX dosage to 120mg / 7 days. At 12 months, 42 patients were evaluable for clinical outcomes. Complete clinical healing at 12 months was achieved in 11 patients (27.5%) and association of PDAI restriction subscore <3 and drainage subscore = 0 was found in 18 patients (42.9%). Thirteen patients (34.2%) from the 25 patients who had received at least 6 months of SC IFX treatment showed clinical healing at 6 months. Out of the 26 patients treated with at least 12 months of SC IFX treatment, clinical healing was achieved in 16 patients (61.5%) at 12 months. Among the 11 patients with clinical healing at 12 months, 8 (72.2%) were treated with SC IFX treatment following more than three IFX IV infusions. None of the 11 patients with available MRI date showed radiological healing at 12 months.

Conclusion

Subcutaneous infliximab following surgical drainage of Crohn’s disease perianal fistula demonstrates high treatment persistence and promising rates of fistula healing.

Disclosure

This study was funded by Celltrion Healthcare France

Introduction

Microplastic particles (MPs), defined as plastic fragments smaller than 5 mm, are pervasive pollutants that accumulate in ecosystems and the human food chain (1). Literature points at various health risks, including the induction of carcinogenesis (2). Emerging evidence from animal models (3) suggests that MPs may influence the gut microbiome, but the impact on the human gut microbiome remains poorly understood.

Aims & Methods

This study aimed to evaluate how various MP types influence gut microbial composition and metabolism using an ex vivo bioreactor model, with a focus on exploring potential carcinogenic effects arising from MP–microbiome interactions.
Stool samples from healthy donors were used to inoculate bioreactor cultures, which were maintained under anaerobic conditions for five days with daily nutrient feeding. These cultures were exposed to five common MP types—polystyrene (PS), polypropylene (PP), low-density polyethylene (LDPE), poly(methyl methacrylate) (PMMA), and polyethylene terephthalate (PET)—at concentrations mimicking both estimated human exposure (4) and higher doses to assess dose-dependence. Cell viability and total bacterial counts, as well as culture pH, were measured throughout the experiment. To further explore potential microbiome and metabolic alterations, 16S rRNA gene sequencing and targeted metabolomics were performed.

Results

MP exposure did not lead to significant changes in total or viable bacterial cell counts. However, MP-treated cultures exhibited a consistent and significant decrease in pH compared to controls, suggesting changes in microbial metabolic activity. Microbiome sequencing revealed plastic-type-dependent alterations in microbial composition, with certain bacterial taxa increasing or decreasing in abundance depending on the MP type. These shifts occurred across multiple genera within diverse families, including Lachnospiraceae, Oscillospiraceae, Enterobacteriaceae, and Ruminococcaceae, with the majority of changes occurring withing the phylum Bacillota. These compositional changes were accompanied by shifts in the metabolomic profiles, some of which correlated with the observed pH changes. Several plastic types induced changes in valeric acid levels, while individual MP types were associated with alterations in distinct metabolites such as uracil, lactic acid, and acetic acid.

Conclusion

This study demonstrates that MPs can affect gut microbial activity and metabolism without significantly altering overall bacterial abundance in the short term. The variation in microbiome response across plastic types highlights the complexity of MP-microbiome interactions. Changes in faecal pH are known to be associated with various gastrointestinal diseases (5). Interestingly, some of the MP-induced changes in microbial composition resembled patterns linked to diseases such as depression and colorectal cancer. In contrast, other changes showed patterns that differed from those typically associated with conditions like Parkinson’s disease and irritable bowel syndrome, highlighting the complexity of these associations and the dependency on the context. The bioreactor model provided a controlled environment for identifying direct MP-microbiome interactions; however, in humans, additional factors like diet, immune response, and individual microbiome variations play a role in determining long-term effects. Exposure duration may also play a critical role in shaping the extent and nature of microbiome alterations (6), underscoring the need for further research into the effects of chronic MP exposure and associated health risks.

References

(1) Mamun, A. A., Prasetya, T. A. E., Dewi, I. R., & Ahmad, M. (2023). Microplastics in human food chains: Food becoming a threat to health safety. The Science of the total environment, 858(Pt 1), 159834. https://doi.org/10.1016/j.scitotenv.2022.159834
(2) Kumar, R., Manna, C., Padha, S., Verma, A., Sharma, P., Dhar, A., Ghosh, A., & Bhattacharya, P. (2022). Micro(nano)plastics pollution and human health: How plastics can induce carcinogenesis to humans?. Chemosphere, 298, 134267. https://doi.org/10.1016/j.chemosphere.2022.134267
(3) Hirt, N., & Body-Malapel, M. (2020). Immunotoxicity and intestinal effects of nano- and microplastics: a review of the literature. Particle and fibre toxicology, 17(1), 57. https://doi.org/10.1186/s12989-020-00387-7
(4) Senathirajah, K., Attwood, S., Bhagwat, G., Carbery, M., Wilson, S., & Palanisami, T. (2021). Estimation of the mass of microplastics ingested - A pivotal first step towards human health risk assessment. Journal of hazardous materials, 404(Pt B), 124004. https://doi.org/10.1016/j.jhazmat.2020.124004
(5) Yamamura, R., Inoue, K. Y., Nishino, K., & Yamasaki, S. (2023). Intestinal and fecal pH in human health. Frontiers in Microbiomes, 2, 1192316.
(6) Yin, L., Yang, M., Teng, A., Ni, C., Wang, P., & Tang, S. (2025). Unraveling Microplastic Effects on Gut Microbiota across Various Animals Using Machine Learning. ACS nano, 19(1), 369–380. https://doi.org/10.1021/acsnano.4c07885

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.