集中带量采购中选与原研头孢地尼口服常释制剂疗效和安全性比较

Comparison of efficacy and safety of national centralized volume-based procurement and original cefdinir oral normal-release preparations

目的比较国家组织集中带量采购(集采)头孢地尼分散片(达力先)与原研头孢地尼胶囊(全泽复)的临床疗效和安全性。方法通过医院信息系统收集2020年1月1日至2021年12月31日首都医科大学宣武医院门诊单次使用头孢地尼患者的性别、年龄、医保类型、感染类型、头孢地尼用药情况、是否合并使用其他抗菌药物, 头孢地尼用药前后血常规、C反应蛋白和肝肾功能等实验室检查结果, 以及头孢地尼不良反应报告资料等信息。对集采中选头孢地尼组(集采组)和原研头孢地尼组(原研组)患者年龄、性别、医保类型、感染类型及是否合并使用其他抗菌药物等进行倾向性评分匹配后, 比较2组患者药物临床应用情况, 间接评价2种药物的疗效。通过比较2组患者用药前后白细胞计数、中性粒细胞百分比及C反应蛋白检测值, 不良反应报告上报情况, 用药前后肝肾功能, 对2药疗效和安全性进行评价。结果共纳入符合入选标准的患者9 514例, 集采组7 037例, 原研组2 477例;经倾向性评分匹配后, 2组患者均为1 268例, 其性别、年龄、感染类型、合并其他抗菌药物等情况比较差异均无统计学意义(均P>0.05)。集采组头孢地尼日剂量、疗程及使用强度均低于原研组[(0.30±0.04)g比(0.35±0.12)g, P<0.001;8(4, 8)d比10(8, 10)d, P<0.001;(3.96±1.70)g比(5.22±2.03)g, P<0.001]。集采组患者用药后白细胞计数、中性粒细胞百分比及C反应蛋白水平均低于用药前[11.2(8.7, 13.8)×10^(9)比7.2(5.5, 9.9)×10^(9), P<0.001;80(74, 87)%比66(56, 73)%, P<0.001;23(10, 64)mg/L比13(6, 44)mg/L, P=0.032]。2组患者用药后均未见头孢地尼药品不良反应报告。用药前2组患者和用药后2组患者丙氨酸转氨酶、天冬氨酸转氨酶、血肌酐及尿素氮水平比较差异均无统计学意义(均P>0.05)。原研组患者用药前后天冬氨酸转氨酶差异有统计学意义[21(18, 23)U/L比23(20, 29)U/L, P=0.040], 丙氨酸转氨酶、血肌酐及尿素氮水平差异无统计学意义(均P>0.05)。2组患者治疗前后肝肾检测值均在参考值范围。结论集采中选头孢地尼分散片(达力先)与原研药头孢地尼胶囊(全泽复)的临床疗效和安全性未见明显差异。

Objective To compare the clinical efficacy and safety of cefdinir dispersible tablets selected in the national centralized volume-based procurement(VBP)and the original drug cefdinir capsules.Methods Clinical data of single-use cefdinir in outpatient of Xuanwu Hospital,Capital Medical University between January 1,2020 and December 31,2021 were collected through the hospital information system.The clinical data included gender,age,type of medical insurance,type of infection,application of cefdinir,whether to combine other antibacterial drugs,laboratory test results such as blood routine,C-reactive protein,liver and kidney function before and after cefdinir treatment,and adverse reaction report of cefdinir.After propensity score matching(PSM)of the age,sex,type of medical insurance,type of infection and whether to combine with other antibacterial drugs in the cefdinir dispersible tablets group selected in the VBP(VBP group)and the original cefdinir group(original group),the clinical application in patients in the 2 groups was compared to indirectly evaluate the efficacy of the 2 drugs.The white blood cell count,neutrophils percentage,and C-reactive protein levels before and after the use of cefdinir was compared to evaluate the efficacy.Adverse drug reaction report of cefdinir and liver and kidney function before and after the use of cefdinir were compared to evaluate the safety.Results A total of 9514 patients treated with cefdinir were entered,including 7037 patients in the VBP group and 2477 patients in the original group.After PSM,each group comprised 1268 patients,the differences in gender,age,type of infection,and combination with other antibacterial drugs were not statistically significant(all P>0.05).The daily dose,course,and use density of cefdinir in the VBP group were lower than those in the original group[(0.30±0.04)g vs.(0.35±0.12)g,P<0.001;8(4,8)d vs.10(8,10)d,P<0.001;(3.96±1.70)g vs.(5.22±2.03)g,P<0.001].The white blood cell count,neutrophils percentage,and C-reactive protein levels after the cefdinir application in patients in the VBP group were lower than those before the use of the cefdinir[11.2(8.7,13.8)×10^(9)vs.7.2(5.5,9.9)×10^(9),P<0.001;80(74,87)%vs.66(56,73)%,P<0.001;23(10,64)mg/L vs.13(6,44)mg/L,P=0.032].No adverse drug reactions related to cefdinir were reported in the 2 groups.The differences in alanine aminotransferase,aspartate aminotransferase,blood creatinine,and urea nitrogen levels in patients between the 2 groups before and after use of cefdinir were not statistically significant(all P>0.05).The difference in aspartate aminotransferase before and after use of the cefdinir in the original group was statistically significant[21(18,23)U/L vs.23(20,29)U/L,P=0.040],and the differences in alanine aminotransferase,blood creatinine,and urea nitrogen levels were not statistically significant(all P>0.05).The detection values of liver and kidney function in the 2 groups before and after use of the cefdinir were within the reference range.Conclusion No significant differences were found in the clinical efficacy and safety between the VBP cefdinir dispersible tablets and the original cefdinir capsules.