講演情報
[SY7-7]Efficacy of Colchicine in Mild-to-Moderate Ulcerative Colitis and Identification of Treatment Response–Associated Molecular Profiles
*Hiroki Kurumi1,2, Kohei Wagatsuma1, Yuta Shimomori1, Kotaro Akita1, Yoshihiro Yokoyama1, Tomoe Kazama1, Hiroshi Nasuno3, Atsushi Yawata4, Hajime Isomoto2, Hiroshi Nakase1 (1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan, 2. Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Japan, 3. Department of Gastroenterology, Kushiro City General Hospital, 4. Department of Gastroenterology and Hepatology, Hakodate Goryoukaku Hospital)
Background
Inflammasome activation is a central driver of innate immune signaling and can amplify intestinal inflammation by releasing IL-1β. Our previous studies suggest that aberrant inflammasome activation contributes to the pathophysiology of ulcerative colitis (UC) in a subset of patients. This study aimed to evaluate the efficacy of colchicine, an inflammasome inhibitor, in patients with mild-to-moderate UC and to identify molecular profiles associated with treatment response using omics analyses.
Methods
Fifteen patients with mild-to-moderate UC (treatment-naïve or 5-ASA–refractory/intolerant) received colchicine 0.5 mg/day, escalated to 1.0 mg at day 14 if non-responding; non-responders at day 28 discontinued, while responders continued through day 84. The primary endpoint was clinical response at day 14. Secondary endpoints included clinical and endoscopic remission at day 84 and safety (CTCAE v5.0). Omics analyses comprised genomic (blood), transcriptomic (colonic mucosa), and gut microbiome analyses (fecal).
Results
Clinical response at day 14 was achieved in 53.3% (8/15), clinical remission at day 84 in 33.3% (5/15), and endoscopic remission in 13.3% (2/15). Adverse events were mild: one patient experienced grade 1 diarrhea, and one grade 1 liver dysfunction. Responders (R) carried MEFV variants in 87.5% (7/8), significantly higher than non-responders (NR) (28.6%, 2/7; p=0.041). Transcriptomic analysis showed enrichment of adaptive immune–related pathways in NR, with significantly elevated KLRG1 expression (p<0.001). Gut microbiome analysis revealed no difference in α-diversity between R and NR, whereas β-diversity differed significantly (PERMANOVA, p=0.049). In R, potentially inflammasome-activating bacteria such as Enterobacter were significantly enriched, whereas NR showed increases in anti-inflammatory taxa (e.g., Bifidobacterium longum), suggesting a compensatory expansion.
Conclusion
Colchicine may benefit a subset of patients with UC who show linked inflammasome signatures across genetics, microbiota, and mucosa.
Inflammasome activation is a central driver of innate immune signaling and can amplify intestinal inflammation by releasing IL-1β. Our previous studies suggest that aberrant inflammasome activation contributes to the pathophysiology of ulcerative colitis (UC) in a subset of patients. This study aimed to evaluate the efficacy of colchicine, an inflammasome inhibitor, in patients with mild-to-moderate UC and to identify molecular profiles associated with treatment response using omics analyses.
Methods
Fifteen patients with mild-to-moderate UC (treatment-naïve or 5-ASA–refractory/intolerant) received colchicine 0.5 mg/day, escalated to 1.0 mg at day 14 if non-responding; non-responders at day 28 discontinued, while responders continued through day 84. The primary endpoint was clinical response at day 14. Secondary endpoints included clinical and endoscopic remission at day 84 and safety (CTCAE v5.0). Omics analyses comprised genomic (blood), transcriptomic (colonic mucosa), and gut microbiome analyses (fecal).
Results
Clinical response at day 14 was achieved in 53.3% (8/15), clinical remission at day 84 in 33.3% (5/15), and endoscopic remission in 13.3% (2/15). Adverse events were mild: one patient experienced grade 1 diarrhea, and one grade 1 liver dysfunction. Responders (R) carried MEFV variants in 87.5% (7/8), significantly higher than non-responders (NR) (28.6%, 2/7; p=0.041). Transcriptomic analysis showed enrichment of adaptive immune–related pathways in NR, with significantly elevated KLRG1 expression (p<0.001). Gut microbiome analysis revealed no difference in α-diversity between R and NR, whereas β-diversity differed significantly (PERMANOVA, p=0.049). In R, potentially inflammasome-activating bacteria such as Enterobacter were significantly enriched, whereas NR showed increases in anti-inflammatory taxa (e.g., Bifidobacterium longum), suggesting a compensatory expansion.
Conclusion
Colchicine may benefit a subset of patients with UC who show linked inflammasome signatures across genetics, microbiota, and mucosa.