Aernoud Fiolet

277 Colchicine reduces extracellular vesicle NLRP3 inflammasome protein levels EVNLRP3 protein levelswere significantly lower in patients treatedwith colchicine (median 1.38 ng/mL) compared to placebo (median 1.58 ng/mL) (difference -0.20 ng/mL, 95% CI -0.37 to -0.03; p=0.025) (Figure 4). NLRP3 protein level in serumwithout EV isolation did not differ between treatment groups (Supplemental Figure 2). Figure 4. Extracellular vesicle NLRP3 protein levels after one year treatment with colchicine or placebo. NLRP3 protein levels in EVs in patients treatedwith colchicine compared to placebo. Boxplots represent medians with inter quartile range and whiskers show 10-90th percentile. Abbreviations: EV, extracellular vesicle; NLRP3, nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 Effect of colchicine on hs-CRP and IL-6 Hs-CRP was significantly lower in patients treated with colchicine (median 0.80 mg/L) compared to placebo (median 1.34 mg/L) (difference -0.54 mg/L, 95% CI -0.58 to -0.12; p<0.005) (Figure 5). IL-6 levels were lower in patients treated with colchicine (median 2.07 ng/L) compared to placebo (median 2.59 ng/L), although this was not statistically significant (difference -0.52 ng/L, 95% CI -0.74 to 0.03; p=0.076) (Figure 5). Levels of hs-CRP correlated significantly with IL-6 levels in patients treated with colchicine (r=0.40, p<0.005) or placebo (r=0.55, p<0.005). Hs-CRP levels did not correlate with EV NLRP3 protein levels in both treatment groups. IL-6 levels correlated with EV NLRP3 protein levels in patients treated with colchicine (r=0.170, p=0.044) (Supplemental Figure 3).

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