Efficacy And Safety Of Fibrates In The Treatment Of Pruritus In Primary Biliary Cholangitis: A Meta-analysis

Objective:Meta-analysis was performed to evaluate the efficacy and safety of fibrates in the treatment of pruritus patients with primary biliary cholangitis(PBC)in order to provide a reference for the clinical management of this type of disease.Methods:Computer searches of Pubmed,Web of Sience,Cochrane Library,Embase,Zhiwang,Chinese Biomedical Literature Database,Vipshop,Wanfang and other databases for relevant studies were supplemented by manual searches for the period of library construction to December 2022,and two evaluators were used to screen the literature,extract data information,and include the quality of the literature The Cochrane Evaluation Manual was used for evaluation,and Rev Man 5.4 and Stata 14.0 were used for statistical and analysis of the data.Results:A total of 15 studies were included,involving a total of 854 patients,including 443 patients treated with UDCA alone and 411 patients treated with UDCA+fibrates combination.Among them,10 studies were on bezafibrate,involving a total of 608 patients,and 5 studies were on fenofibrate,involving 246 patients.The results of meta-analysis showed: 1.Effectiveness:(1)Number of pruritus: UDCA combined with fibrates was superior to UDCA alone in improving pruritus symptoms in patients with PBC(OR=9.31,95%CI=(5.69,15.24),P<0.00001),bezafibrate(OR=9.23,95%CI=(5.44,15.64),P<0.00001)may be superior to fenofibrate(OR=9.77,95%CI=(2.54,37.61),P=0.0009).(2)Itching score: UDCA combined with bezafibrate showed an advantage over UDCA alone in improving the itching score of PBC patients(MD=-3.00,95%CI=(-3.40,-2.60),P<0.00001).(3)UDCA combined with fibrates reduced ALP(bezafibrate: MD=-146.54,95%CI=(-186.44,-106.65),P<0.00001;fenofibrate: MD=-121.78,95%CI=(-145.94,-97.62),P<0.00001),GGT(bezafibrate:MD=-74.17,95%CI=(-98.56,-49.78),P<0.00001;fenofibrate: MD=-137.86,95%CI=(-222.46,-53.26),P=0.001),ALT(bezafibrate: MD=-16.42,95%CI=(-21.49,-11.35),P < 0.00001;fenofibrate: MD=-19.63,95%CI=(-29.55,-9.70),P=0.0001),AST(bezafibrate: MD=-5.96,95%CI=(-7.44,-4.48),P< 0.00001;fenofibrate: MD=-10.55,95%CI=(-17.80,-3.31),P=0.004),TBIL(bezafibrate: MD=-3.53,95%CI=(-4.02,-3.04),P<0.00001;fenofibrate:MD=-13.27,95%CI=(-21.61,-4.94),P=0.002),TC(bezafibrate: MD=-37.14,95%CI=(-43.46,-30.82),P<0.00001;fenofibrate:MD=-0.62,95%CI=(-1.10,-0.13),P=0.01),TG(bezafibrate: MD=-30.98,95%CI=(-36.59,-25.37),P<0.00001;fenofibrate:MD=-0.35,95%CI=(-0.56,-0.14),P=0.001),Ig M(bezafibrate:MD=-67.36,95%CI=(-100.62,-34.09),P<0.0001;fenofibrate:MD=-174.81,95%CI=(-299.06,-50.6),P=0.006).2.Safety:(1)Adverse events:UDCA combined with bezafibrate(OR=2.38,95%CI=(1.38,4.09),P=0.002)or fenofibrate(OR=20.75,95%CI=(4.98,86.50),P<0.0001)may result in more adverse events than UDCA alone.(2)Cr:There was no significant difference in Cr between UDCA combined with fibrates(MD=1.29,95%CI=(-1.57,4.16),P=0.38).Conclusions:Combination therapy of UDCA with fibrates was effective in relieving pruritus symptoms and significantly improving pruritus scores in patients with PBC pruritus;combination therapy improved biochemical function in patients with PBC pruritus and was more effective than UDCA monotherapy in reducing ALP,GGT,ALT,AST,TBIL,TC,TG,and Ig M levels;combination therapy may be more prone to adverse reactions,including gastrointestinal discomfort such as heartburn and nausea,abdominal pain,and transient myalgia without elevated kinases,did not result in elevated Cr levels,and the occurrence of adverse events was not quantitatively significant,with most symptoms being mild and resolving quickly without affecting continued treatment with the drug.