摘要
目的:探讨生物类似药德谷门冬双胰岛素(IDegAsp)与原研药诺和佳®治疗成年2型糖尿病(T2DM)患者的安全性是否存在差异,并分析其安全性风险相关的影响因素。方法:基于一项关于生物类似药IDegAsp疗效与安全性的Ⅲ期临床试验,本研究首先将182例接受IDegAsp生物类似药治疗的试验组和183例接受原研药诺和佳®治疗的对照组患者纳入安全性分析集(SS),并对两治疗组发生的不良事件(AE)、不良反应(ADR)、严重不良事件(SAE)以及特别关注不良事件(AESI)的总体发生率和累积发生率进行组间差异性分析;其次,采用热图对两治疗组发生的不良事件按PT、SOC分层进行可视化展示;最后,通过Cox回归筛选出不良事件的独立影响因素。结果:试验组和对照组不良事件的发生率分别为75.82%和82.51%,器官系统分类(SOC)、首选术语(PT)层级的不良事件频数分布情况大致相同。两治疗组AE、ADR、SAE以及AESI的总体发生率比较,组间差异均无统计学意义(P值分别为0.116、0.223、0.440、0.784),累积发生率比较的组间差异也均无统计学意义(P值分别为0.460、0.122、0.454、0.718)。单因素Cox回归分析结果表明研究药物治疗分组并非是导致不良事件发生风险增加的危险因素。多因素Cox回归最终筛选出的7个独立影响因素,按风险因子表达效应降序排列依次分别为:糖化血红蛋白(HbA1c)、最大血糖波动幅度(LAGE)、胰岛素类别、联合用药数量、高密度脂蛋白(HDLC)、体重指数(BMI)、高脂血症。结论:生物类似药德谷门冬双胰岛素AE发生风险相关的7个独立影响因素中,除BMI(≥24.0 kg·m^(-2))为降低AE发生风险的保护因素外,其他6个因素均为增加AE发生风险的危险因素。与原研药诺和佳®比较而言,使用德谷门冬双胰岛素生物类似药治疗T2DM并不会增加不良事件的发生风险,两者总体安全性特征相似,德谷门冬双胰岛素生物类似药可安全替代原研药用于T2DM治疗。
Objective:To evaluate the safety difference and to investigate the safety related factors of insulin degludec and insulin aspart injections(biosimilar IDegAsp and original Ryzodeg®)in the treatment of type 2 diabetes mellitus(T2DM).Methods:Analysis were performed on the safety data derived from a phase 3,randomized,open-label,parallel-group and multicenter clinical trial in Chinese T2DM patients.First of all,182 subjects from the experimental group and 183 subjects from the control group,subcutane-ously administered with IDegAsp and Ryzodeg®respectively,were ultimately included in the safety analy-sis set(SS).Meanwhile the overall and cumulative incidence of various kinds of safety outcomes,includ-ing adverse events(adverse events,AE),adverse drug reactions(ADR),severe adverse events(SAE)and adverse events of special interest(AESI),were analyzed in this study.Subsequently,this study compared the frequency distribution of AE at SOC and PT levels.Finally,the independent influencing factors of AE were screened through Cox regression analysis.Results:The incidence rates of AE in the experimental group and control group were 75.82%and 82.51%,respectively.The frequency distributions of AE at the SOC and PT levels in the two treatment groups were roughly the same.The inter group comparison of safety outcome indicators showed that there was no statistically significant difference in the overall inci-dence of AE,ADR,SAE and AESI between the two groups(P values were 0.116,0.223,0.440 and 0.552,respectively).Meanwhile there was no statistically significant difference in the cumulative incidence of AE,ADR,SAE and AESI between the two groups(P values were 0.460,0.122,0.454 and 0.718,respectively).The results of univariate Cox regression analysis showed that the risk of AE would not be increased by treatment grouping of the investigated drugs.Seven independent influencing factors were ulti-mately identified by multiple Cox regression analysis.The seven factors,arranged by descending expres-sion effects of risk,were glycohaemoglobin(HbA1c),largest amplitude of glycemic excursion(LAGE),previ-ously treated insulin type,the number of combined drugs,high density lipoprotein(HDLC),body mass index(BMI)and hyperlipidaemia.Conclusion:Among the seven independent influencing factors related to the risk of AE occurred in T2DM patients treated with IDegAsp or Ryzodeg®,except for the BMI(≥24.0 kg·m^(-2))is considered to be a protective factor for reducing the risk of AE,the other six factors are all risk factors for increasing the risk of AE.Consequently,the use of biosimilar IDegAsp in the treatment of T2DM will not increase the incidence rate of AE,and the overall safety profile is similar to original Ryzo-deg®.Therefore the biosimilar IDegAsp can safely replace the original Ryzodeg®for the T2DM treatment.
作者
鲜树雍
黄哲
曹海燕
XIAN Shuyong;HUANG Zhe;CAO Haiyan(College of Business Administartion,Shenyang Pharmaceutical University,Shenyang 110000,China;Huish-eng Biopharmaceutical Co.,Ltd.,Tonghua,Jilin 135000,China)
出处
《药学与临床研究》
2025年第1期18-25,共8页
Pharmaceutical and Clinical Research
