埃索美拉唑、克拉霉素、阿莫西林序贯疗法与三联疗法治疗Hp阳性十二指肠溃疡的疗效及经济学对比

Comparison of the Efficacy and Economy of Sequential Therapy and Triple Therapy of Esomeprazole Combined with Clarithromycin and Amoxicillin for Hp Positive Duodenal Ulcer

目的对比分析埃索美拉唑、克拉霉素、阿莫西林序贯疗法与标准三联疗法治疗幽门螺杆菌(Hp)阳性十二指肠溃疡临床疗效,为Hp的临床根治提供借鉴和参考。方法选取2015年1月至2016年6月我院收治的290例Hp阳性十二指肠溃疡患者进行前瞻性研究。按就诊顺序将患者分为改良序贯组(97例),给予改良序贯疗法:前5天每天2次口服埃索美拉唑(20 mg)+克拉霉素(500 mg),后5天每天2次口服埃索美拉唑(20 mg)+克拉霉素(500 mg)+阿莫西林(1 000 mg);传统序贯组(97例),给予传统序贯疗法:前5天每天2次口服埃索美拉唑(20 mg)+阿莫西林(1 000 mg),后5天每天2次口服埃索美拉唑(20 mg)+克拉霉素(500 mg)+阿莫西林(1 000 mg);标准三联组(96例),给予标准三联疗法:连续10天每天2次口服埃索美拉唑(20 mg)+克拉霉素(500 mg)+阿莫西林(1 000 mg)。所有药物均为每日给药2次,疗程均为10天。观察3组患者的Hp根除率和不良反应发生情况,进行3组治疗方案的疗效评价和成本分析。结果共275例患者完成了最终随访研究,改良序贯组、传统序贯组和标准三联组的Hp根除率分别为88.66%(ITT)和92.47%(PP)、84.54%(ITT)和89.13%(PP)、72.92%(ITT)和77.78%(PP),改良序贯组和传统序贯组均明显高于标准三联组(P<0.05)。共247例患者分离出Hp并培养成功,其中克拉霉素耐药性达13.36%(33/247),无阿莫西林耐药菌株。改良序贯组、传统序贯组和标准三联组的克拉霉素耐药Hp根除率分别为为81.82%(9/11)、80.00%(8/10)和33.33%(4/12),改良序贯组和传统序贯组均显著高于标准三联组(P<0.05);而敏感菌株的患者治疗后,3组Hp根除率分别为93.90%(77/82)、90.24%(74/82)和84.62%(66/78),组间比较无显著性差异(P>0.05)。三组患者治疗后的临床总有效率和不良反应发生率比较均无显著性差异(P>0.05)。改良序贯组和传统序贯组的成效比及增量成效比均略优于标准三联组。结论埃索美拉唑、克拉霉素和阿莫西林序贯疗法和标准三联疗法均可有效治疗Hp阳性十二指肠溃疡,但序贯疗法对Hp根除率更高,且具有更高的药物经济性。至于改良贯疗法而言,在本次研究中并未表现出优势,仍需进一步探索。

objective To analyze and compare the efficacy and economy of sequential therapy and triple therapy of esomeprazole combined with clarithromycin and amoxicillin for Helicobacter pylori (Hp) positive duodenal ulcer, and provide the reference for eradication of Hp. Methods 290 patients with Hp positive duodenal ulcer from January 2015 to June 2016 in our hospital were studied prospectively. All of the patients were divided into three groups according to the visiting sequence, including 97 cases who received the modified sequential therapy as the modified sequential group, 97 cases who received the traditional sequential therapy as the traditional sequential group, and 96 cases who received the standard triple therapy as the standard triple group.Patients in the modified sequential group were provided 20 mg of esomeprazole, 500 mg of clarithromycin twice daily for the first 5 days, followed by 20 mg of esomeprazole, 500 mg of clarithromycin, and 1 000 mg of amoxicillintwice daily for the remaining 5 days. Patients in the traditional sequential group were given 20 mg of esomeprazole, 1 000 mg of amoxicillin twice daily for the first 5 days, followed by 20 mg of esomeprazole, 500 mg of clarithromycin, and 1 000 mg of amoxicillin twice daily for the remaining 5 days. Patients in the standard triple group received 20 mg of esomeprazole, 500 mg of clarithromycin,and 1 000 mg of amoxicillin twice daily for standard 10-day therapy. All of the drugs were administered 2 times a day, the course of treatment was 10 days. The Hp eradication rate and adverse reaction of 3 groups were observed, the efficacy and cost analysis of the 3 groups were evaluated. Results A total of 275 patients were followed-up at the end of study, the Hp eradication rates of the modified sequential group, the traditional sequential group and the standard triple group were 88.66%(ITT) and 92.47%(PP), 84.54%(ITT) and 89.13% (PP), 72.92%(ITT) and 77.78%(PP).The Hp eradication rates of the modified sequential group and traditional sequential group were significantly higher than those of the standard triple group (P < 0.05). 247 cases of Hp were isolated and cultured successfully, resistant rate of clarithromycin was 13.36% (33/247), no amoxicillin resistant strains. The eradication rates of clarithromycin resistant Hp in the modified sequential group, traditional sequential group and standard triple group were 81.82% (9/11), 80.00% (8/10) and 33.33% (4/12) respectively, and the eradication rate in the modified sequential group and traditional sequential group were significantly higher than that in the standard triple group (P < 0.05). The eradication rates of sensitive strains in three groups were 93.90% (77/82), 90.24% (74/82) and 84.62% (66/78) respectively,without significant difference among the three groups (P > 0.05). There was no significant difference in the total effective rate and incidence of adverse reactions among the three groups (P > 0.05). The cost-effectiveness ratio and incremental cost-effectiveness ratio of the modified sequential group and traditional sequential group were slightly better than those of the standard triple group.Conclusion The sequential therapy and triple therapy of esomeprazole combined with clarithromycin and amoxicillin can be effective for Hp positive duodenal ulcer. However, the sequential therapy has higher Hp eradication rate and economic value than the standard triple therapy. The modified improved penetration therapy did not show any advantages in this study and still need to be further explored.