Efficacy and safety of a selective URAT1 inhibitor SHR4640 in Chinese subjects with hyperuricaemia: a randomized controlled phase II study.

OBJECTIVE: To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor, in Chinese subjects with hyperuricaemia. METHODS: This was a randomized double-blind dose-ranging phase II study. Subjects whose serum uric acid (sUA) levels were ≥480 µmol/l with gout, ≥480 µmol/l without gout but with comorbidities, or ≥540 µmol/l were enrolled. Subjects were randomly assigned (1:1:1:1:1) to receive once daily 2.5 mg, 5 mg, 10 mg of SHR4640, 50 mg of benzbromarone or placebo, respectively. The primary end point was the proportion of subjects who achieved target sUA level of ≤360 µmol/l at week 5. RESULTS: 99.5% of subjects (n = 197) were male and 95.9% of subjects had gout history. The proportions of subjects who achieved target sUA at week 5 were 32.5%, 72.5% and 61.5% in the 5 mg, 10 mg SHR4640 and benzbromarone groups, respectively, significantly higher than the placebo group (0%; P < 0.05 for 5 mg and 10 mg SHR4640 group). The sUA was reduced by 32.7%, 46.8% and 41.8% at week 5 with 5 mg, 10 mg SHR4640 and benzbromarone, respectively, vs placebo (5.9%; P < 0.001 for each comparison). The incidences of gout flares requiring intervention were similar among all groups. Occurrences of treatment-emergent adverse events (TEAEs) were comparable across all groups, and serious TEAEs were not reported. CONCLUSIONS: The present study indicated a superior sUA-lowering effect and well tolerated safety profile after 5-week treatment with once-daily 5 mg/10 mg of SHR4640 as compared with placebo in Chinese subjects with hyperuricaemia. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03185793.

[Correlations between serum 25-hydroxyvitamin D and cytokines in patients newly diagnosed with systemic lupus erythematosus].

Objective To investigate the correlations between serum 25-hydroxyvitamin D (25-OH-VitD) and serum cytokines of interferon (IFN)-α2, interleukin(IL)-6, IL-10, and IL-17A in Chinese Han patients newly diagnosed with systemic lupus erythematosus (SLE). Methods This study recruited 86 Chinese patients newly diagnosed with SLE and 73 healthy volunteers. The serum 25-OH-VitD was detected using ELISA. The serum levels of IFN-α2, IL-6, IL-10 and IL-17A were detected using Luminex liquichip. The associations between serum 25-OH-VitD and serum cytokines, clinical manifestations and laboratory findings were analyzed using Spearman linear correlation analysis. Results The serum 25-OH-VitD was significantly lower in SLE patients than in healthy controls. The serum 25-OH-VitD was positively correlated with serum C3, negatively correlated with serum IL-17A and 24 hour urine protein excretion, but not obviously correlated with serum IFN-α2, IL-6 and IL-10. Conclusion The serum 25-OH-VitD decreases in Chinese patients newly diagnosed with SLE and it is negatively correlated with serum IL-17A.