P0870Dynamic profiling of circulating micro-RNAs reveals early signatures of infliximab response in ulcerative colitis

Abstract Background Micro-RNAs (miRNAs) are small non-coding RNAs mediating post-transcriptional gene silencing. We conducted a prospective study to identify circulating miRNAs associated with treatment response in patients with ulcerative colitis (UC) undergoing infliximab therapy. Methods Patients with moderate-to-severe UC starting intravenous infliximab were included and classified after 12 months as “responders” (achieving combined clinical-endoscopic remission, i.e. Mayo endoscopic subscore=0 and absence of symptoms) or “non-responders”. Plasma samples were collected at baseline and post-induction. Clinical and endoscopic assessments were performed at baseline and at 12 months or earlier in case of treatment failure. Circulating miRNAs were analysed using the Nanostring Human v3 miRNA Assay. Differential expression analysis, target genes identification, and receiver operating characteristic (ROC) analyses were performed. Results Twelve patients were included in this study: 6 responders, 6 non-responders (Table 1). Distinct miRNA expression patterns emerged when comparing the two groups. At baseline (Figure 1A), target genes of upregulated miRNAs in responders were mostly involved in immune regulation pathways, particularly T-cell differentiation and complement activation. In contrast, targets of downregulated miRNAs were associated with TGF-β response, epithelial-mesenchymal transition (EMT), epithelial development, and fibroblast proliferation. After induction (Figure 1B), enrichment analysis of target genes of upregulated miRNAs revealed modulation of pathways related to epithelial and T-cell differentiation. Consistent with baseline findings, targets of downregulated miRNAs in responders were significantly enriched in pathways involved in epithelial development, EMT, TGF-β receptor signaling, and hypoxia-associated pathways. Among the evaluated candidates, the best predictors of combined remission were miRNAs of the miR-200 family. At baseline, miR-200b-3p showed a trend towards significance area under the ROC curve (AUC)=0.833, p = 0.065, while after induction, miR-200a-3p was the most accurate and significant predictor of 12-month combined remission (AUC=0.933, p = 0.017) (Figure 1C-D). Both miRNAs belong to the TGF-β-related regulatory network, consistent with the recurrent involvement of epithelial development and TGF-β signaling across time points. Conclusion Our pilot study suggests that specific circulating miRNA signatures may serve as early biomarkers of treatment response in UC. Notably, miR-200a-3p emerged as a promising candidate, demonstrating strong predictive performance for 12-month combined remission when assessed at the end of infliximab induction. These preliminary findings warrant validation in larger, prospective cohorts. Conflict of interest: Dr. Innocenti, Tommaso: Speaker fees from Aurora Biofarma, and Ferring. Travel grants from Abbvie, Alfasigma, Celltrion, Eli Lilly, Ferring, Malesci, Pfizer. Pillozzi, Serena: No conflict of interest Scolari, Federico: No conflict of interest Menicacci, Beatrice: No conflict of interest Iamello, Rocco Gabriele: No conflict of interest Picariello, Lucia: No conflict of interest Curto, Armando: No conflict of interest Ceni, Elisabetta: No conflict of interest Bagnoli, Siro: No conflict of interest Polvani, Simone: No conflict of interest Mello, Tommaso: No conflict of interest Milani, Stefano: No conflict of interest Galli, Andrea: No conflict of interest Dragoni, Gabriele: Grant: ECCO Grant 2020 ECCO/AOCC Travel Grant 2021 ECCO IIS Registry Grant 2023 ECCO/IBUS Research Grant 2023 Personal Fees: - Speaker’s fees from: 2020: Novartis 2022: Janssen 2023: Alfasigma, Janssen, Pfizer, and Takeda 2024: Ferring, Johnson & Johnson, Eli Lilly, Pfizer, and Takeda 2025: Abbvie, Alfasigma, Ferring, Eli Lilly, LionHealth, Pfizer, Takeda - Advisory board fees from: 2023: Celltrion Healthcare and Pfizer 2024: AbbVie 2025: AbbVie, Johnson & Johnson