Efficacy And Safety Analysis Of Fenofibrate Combinedwith Febuxostat/Benzbromarone In The Treatment Of Gout With Hypertriglyceridemia

Objective:Compare the efficacy and safety of fenofibrate combined with febuxostat/benzbromarone in the treatment of primary gout with hypertriglyceridemia.Methods:Type of experimental design for single center,controlled clinical trial(clinical trial registration number ChiCTR1800018160).According to the criteria of inclusion and exclusion,140 patients in the gout clinic of Qingdao University from December 2017 to December 2018 were selected as experimental subjects.They were randomly assigned to Group 1(febuxostat+fenofibrate)and Group 2(benzbromarone+fenofibrate),70 cases in each group.Treatment of Group 1:febuxostatin 20mg qd+fenofibrate 200mg qd.Treatment of Group 2:benbromarone 25mg qd+fenofibrate 200mg qd.The two groups were given basic colchicine and sodium bicarbonate at the same time and required to be in low-purine diet and drink water more than 2000ml/d.According to the corresponding group test scheme treat for 14 weeks,and deteced serum uric acid(SUA),transaminase(ALT/AST),fasting blood glucose(FBG),triglyceride(TG),total cholesterol(TC),serum creatinine(CREA),fraction excretion of uric acid(FEUA)and adverse reactions at week 2th,6th,10th and 14th respectively.EmpowerStats software was used for statistical analysis.Intentional analysis(ITT)was used to treat cases of loss.Quantitative data were compared with T test.Qualitative data were analyzed by chi-square test.The repeated measurement random effect model analysis was used in the comparison of relevant indicators in different visiting points.The statistical result P<0.05 was statistically significant.Results:A total of 140 patients were included in the study.70 cases were enrolled in each group.64 cases were followed up in Group 1,of which 6 cases were eliminated because of the loss of visits(3 cases)and poor compliance(3cases).58 cases were followed up in Group2,of which 12 cases were eliminated because of the loss of visits(4 cases)?poor compliance(2 cases)and no treatment(6 cases).Primary end points:1.The rate of SUA<360 mol/L in the 14th week was 67.14%vs 60.94%in two groups(x~2=0.560,P=0.454).2.In the 14th week,the percentage of SUA decreased from baseline in the two groups was(40.5±11.9)%vs(35.8±15.3)%(t=1.997,P=0.048),and the difference was statistically significant.Secondary end points:1.The percentage reduction of TG in the 14th week from the baseline was(43.78±16.02)%vs(40.79±19.72)%(t=0.969,P=0.334),with no statistical significance.The percentage reduction of TC in the 14th week between the two groups was(15.43±9.89)%vs(14.86±9.92)%(t=0.332,P=0.741).2.The proportion of uric acid<300 mol/L was 40.00%vs 34.38%(x~2=0.452,P=0.501)in the two groups in the 14th week,with no statistical difference.3.FEUA in group 2 was higher than group 1,.The last visit was increased(38.60±49.91)vs(73.67±48.15)%compared with baseline(t=3.238,P=0.002).Safety analysis 1.The incidence of abnormal liver function in two groups was22.86%vs 12.5%,respectively,with no significant difference(x~2=2.439,P=0.118).2.During the treatment,there was no significant difference in the level of estimated glomerular filtration rate(eGFR)between the two groups.The percentage reduction of eGFR between the two groups in the 14th week was(8.09±12.03)%and(11.26±11.10)%(t=1.580,P=0.116),with no statistical significance.eGFR in the two groups in the 14th week decreased from the baseline was(8.86±12.00)vs(11.46±12.41)(ml/min/1.73m~2),which were statistically significant from the baseline respectively(t=6.178vs7.389,P<0.001).Followed up CREA within 2-4 weeks after the end of the experiment,64 patients(34 cases in group 1and 32cases in group 2)comed back.There was no statistical difference between the eGFR in the follow-up state and the baseline state(t=1.009vs0.694,P=0.320vs0.493).3.Other adverse reactions like gastrointestinal tract reaction and gout flare can be found.We didn't see a skin rash,fever,high blood pressure and adverse reactions such as new kidney stones,cardiovascular events in both groups,the adverse reactions between the two groups did not see the difference.ConclusionIn patients with gout combined with hypertriglyceridemia,all of the two groups can achieve a good effect of reducing uric acid and improve blood lipid metabolism.The range of reducing uric acid of fenofibrate combined with febuxostat is greater than that of fenofibrate combined with benbromomarone,and attention should be paid to the monitoring of liver and kidney function in the application process.