宁夏地区克拉霉素敏感性检测指导下精准与经验性含铋剂四联疗法在首次幽门螺杆菌根除治疗中的疗效分析

Efficacy analysis of precise and empirical bismuth-containing quadruple therapy guided by clarithromycin sensitivity testing in the first eradication of Helicobacter pylori in Ningxia

目的探讨宁夏地区克拉霉素敏感性检测指导下精准与经验性含铋剂四联疗法在首次根除幽门螺杆菌(H.pylori)中的疗效。方法选取2022年8月12日至2023年3月22日于宁夏回族自治区人民医院、宁夏回族自治区人民医院宁南医院、中卫市人民医院、吴忠市盐池县人民医院、石嘴山市平罗县人民医院就诊的经14C-尿素呼气试验(14C-UBT)初次诊断为H.pylori阳性患者600例,采用随机数字表法分为经验性治疗组(以下简称经验组)、基因检测组(以下简称基因组)、药敏试验组(以下简称药敏组),每组200例患者。经验组未行药敏试验和基因检测。基因组和药敏组分别经基因检测和药敏试验明确对克拉霉素敏感,并排除耐药患者。3组患者均接受相同克拉霉素含铋剂四联治疗方案,采用意向性治疗集(ITT)和符合方案集(PP)分析比较3组的H.pylori根除率。基于ITT计算成本-效果比(CER)和增量成本-效果比(ICER)进行成本-效果和敏感性分析。统计学方法采用卡方检验。结果ITT中经验组、基因组、药敏组分别纳入200、126、168例患者,PP中3组分别纳入190、123、164例患者。ITT分析结果显示,经验组、基因组、药敏组的H.pylori根除率分别为80.5%(161/200)、94.4%(119/126)、95.2%(160/168),PP分析结果显示3组的H.pylori根除率分别为84.7%(161/190)、96.7%(119/123)、97.6%(160/164),差异均有统计学意义(χ^(2)=25.39、24.93,均P<0.001)。ITT和PP分析中基因组、药敏组的H.pylori根除率均高于经验组(χ^(2)=12.40、17.80、11.42、17.13,均P<0.001)。成本-效果分析显示,经验组、基因组、药敏组的治疗直接成本分别为400.8、729.2、779.2元,3组CER分别为4.98、7.72、8.18元/%。基因组、药敏组相较于经验组的ICER分别为23.6、25.7元/%。敏感性分析显示,当基因检测费用下调或上调20%,基因组相较于经验组的ICER分别为21.8、25.5元/%;当药敏试验费用下调或上调20%,药敏组相较于经验组的ICER分别为23.3、28.2元/%;当胃镜检查费用下调或上调20%,基因组相较于经验组的ICER分别为20.8、26.5元/%,药敏组相较于经验组的ICER分别为23.0、28.4元/%。结论若在宁夏地区应用克拉霉素含铋剂四联方案作为首次根除H.pylori方案,为达到满意的根除H.pylori疗效,并且患者可以接受H.pylori根除率每增加1%需额外支付23.6或25.7元,建议进行克拉霉素耐药性检测后给予精准化治疗。

Objective To explore the efficacy of precise and empirical bismuth-containing quadruple therapy guided by clarithromycin sensitivity testing in the first eradication of Helicobacter pylori(H.pylori)in Ningxia.Methods From August 12,2022 to March 22,2023,600 patients diagnosed as H.pylori-positive by 14C-urea breath test(14C-UBT)for the first time in People′s Hospital of Ningxia Hui Autonomous Region,Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region,Zhongwei People′s Hospital,Yanchi County People′s Hospital,and Pingluo People′s Hospital were selected,and divided into empirical treatment group(hereinafter referred to as the empirical group),genetic testing group(hereinafter referred to as the genetic group),and drug sensitivity testing group(hereinafter referred to as the drug sensitivity group)by using random number table with 200 patients in each group.The empirical group did not undergo drug sensitivity testing and genetic testing,while the genetic and drug sensitivity groups were confirmed to be sensitive to clarithromycin through genetic testing and drug sensitivity testing,and the patients with drug-resistant were excluded,respectively.All the patients of the 3 groups received the same clarithromycin bismuth-containing quadruple therapy.Intention-to-treat(ITT)and per-protocol(PP)analyses were performed to compare the eradication rates of H.pylori among 3 groups.Cost-effectiveness ratio(CER)and incremental cost-effectiveness ratio(ICER)were used for cost-effectiveness and sensitivity analysis based on the ITT.Chi-square test was used for statistical analysis.Results There were 200,126,and 168 patients included in the empirical group,genetic group,and drug sensitivity group in ITT analysis,and 190,123,and 164 patients were enrolled in the 3 groups in PP analysis,respectively.The results of ITT analysis showed that the eradication rates of H.pylori in the empirical group,genetic group,and drug sensitivity group were 80.5%(161/200),94.4%(119/126),and 95.2%(160/168),respectively.The results of PP analysis indicated that the eradication rates of H.pylori in the 3 groups were 84.7%(161/190),96.7%(119/123),and 97.6%(160/164),respectively,and the differences were statistically significant(χ^(2)=25.39 and 24.93,both P<0.001).The H.pylori eradication rates of genetic group and drug sensitivity group were both higher than that of empirical group in ITT and PP analysis(χ^(2)=12.40,17.80,11.42,and 17.13;all P<0.001).The cost-effectiveness analysis showed that the direct treatment cost of the empirical group,genetic group,and drug sensitivity group was 400.8,729.2,and 779.2 yuan,respectively,and the CER was 4.98,7.72,and 8.18 yuan/%,respectively.Compared to the empirical group,the ICER of the genetic group and drug sensitivity group was 23.6 and 25.7 yuan/%,respectively.The sensitivity analysis demonstrated that,when the cost of genetic testing reduced or increased by 20%,the ICER of the genetic group compared to the empirical group was 21.8 or 25.5 yuan/%,respectively.When the cost of drug sensitivity testing reduced or increased by 20%,the ICER of the drug sensitivity group compared to the empirical group was 23.3 or 28.2 yuan/%.When the cost of gastroscopy reduced or increased by 20%,the ICER of the genetic group compared to the empirical group was 20.8 or 26.5 yuan/%,and the ICER of the drug sensitivity group compared to the empirical group was 23.0 or 28.4 yuan/%,respectively.Conclusion In Ningxia,if the clarithromycin bismuth-containing quadruple regimen is applied as the first H.pylori eradication regimen,in order to achieve the clinical eradication efficacy of H.pylori,and the patients can accept an additional payment of 23.6 or 25.7 yuan for each 1%increasing in the H.pylori eradication rate,then the precision treatment after clarithromycin resistance test is recommended.