Circulating microRNAs as biomarkers of disease activity and treatment response in Crohn’s disease patients receiving infliximab or vedolizumab: a longitudinal cohort study
Abstract
Background and aims Validated biomarkers of biologic response in Crohn’s disease (CD) are lacking. We assessed whether serum microRNAs (miRNAs) track disease activity and predict outcomes during biologic induction in CD. Methods Thirty-nine adults with active CD initiating infliximab (n = 20) or vedolizumab (n = 19) and 10 controls were studied at a single centre. Serum was sampled at the first and fourth infusions. Six target miRNAs were qPCR-quantified and normalised to the geometric mean of miR-93-5p and miR-425-5p. Harvey–Bradshaw Index, C-reactive protein, faecal calprotectin and Simple Endoscopic Score for CD were recorded at baseline, post-induction and 12 months. Four pre-specified analysis families were tested with false discovery rate (FDR) correction for multiple testing. This was a single-centre, exploratory, hypothesis-generating study. Results miR-21-5p and miR-146b-5p were significantly reduced in CD versus controls (q < 0.05). Baseline miR-146b-5p inversely predicted post-induction CRP independently of baseline disease severity (partial r = −0.46, p = 0.010), supporting it as a candidate severity-independent predictor of biochemical response. Post-induction miR-424-5p strongly tracked concurrent inflammation (faecal calprotectin: Spearman ρ = +0.52, q = 0.004; CRP: ρ = +0.44, q = 0.030), these associations remained significant after adjustment for baseline disease severity, after leave-one-out removal of single patients, and under single-reference normalisation. An exploratory post-hoc analysis linked treatment-induced miR-106a-5p upregulation to penetrating (Montreal B3) disease (permutation p = 0.019). Conclusion Serum miRNAs offer novel predictive (baseline miR-146b-5p and miR-106a-5p) and concurrent (post-induction miR-424-5p) biomarker signals during biologic induction in CD, providing information complementary to faecal calprotectin. Prospective independent validation is warranted before clinical translation.