延长或转换为艾米替诺福韦治疗在慢性乙型肝炎患者中的疗效评估:一项Ⅲ期随机对照研究

Efficacy evaluation of extending or switching to tenofovir amibufenamide in patients with chronic hepatitis B:a phaseⅢrandomized controlled study

目的研究慢性乙型肝炎患者(CHB)分别初始接受艾米替诺福韦(TMF)或富马酸替诺福韦酯(TDF)治疗96周后,延长或转换为TMF治疗48周的疗效特点。方法CHB患者按2∶1随机分配至每日1次口服TMF 25 mg或TDF 300 mg,持续96周,然后进入48周的开放标签TMF 25 mg治疗期,评估包括病毒学、血清学、生化学应答和组织学评价方面的疗效差异。据资料不同采用McNemar检验、t检验或Log-Rank检验进行统计学分析。结果TMF初治组共593例,TDF转换组共287例受试者完成144周治疗或达到研究终点。第144周时,整体人群获得乙型肝炎病毒(HBV)DNA<20 IU/ml的比例分别为86.2%和83.3%;在基线HBV DNA≥8 log 10 IU/ml的人群中,该比例分别为78.1%和73.8%;无患者新发耐药。两组第144周HBeAg转阴率和血清学转换率较96周仍有进一步显著提升,3年合计阴转率约为35%。同时TDF组在转换治疗48周后丙氨酸转氨酶(ALT)复常率进一步提高了11.4%,肝纤维化指数(FIB-4)也获得了显著改善。结论CHB患者经过144周TMF的治疗,可维持良好的病毒学应答和生化学应答。TDF治疗96周后,转换至TMF 48周可使患者获得生化学应答的提高。

ObjectiveIn chronic hepatitis B(CHB)patients with previous 96-week treatment with tenofovir amibufenamide(TMF)or tenofovir disoproxil fumarate(TDF),we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.MethodsEnrolled subjects who were previously assigned(2:1)to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks.Efficacy was evaluated based on virological,serological,biological parameters,and fibrosis staging.Statistical analysis was performed using the McNemar test,t-test,or Log-Rank test according to the data.Results593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144,with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2%and 83.3%,respectively,and 78.1%and 73.8%in patients with baseline HBV DNA levels≥8 log10 IU/ml.Resistance to tenofovir was not detected in both groups.For HBeAg loss and seroconversion rates,both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35%in each group.However,HBsAg levels were less affected during 96 to 144 weeks.For patients switched from TDF to TMF,a substantial further increase in the alanine aminotransferase(ALT)normalization rate was observed(11.4%),along with improved FIB-4 scores.ConclusionAfter 144 weeks of TMF treatment,CHB patients achieved high rates of virological,serological,and biochemical responses,as well as improved liver fibrosis outcomes.Also,switching to TMF resulted in significant benefits in ALT normalization rates(NCT03903796).