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目的：本研究基于网状Meta分析，旨在比较不同骨改良药物（bone-modifying agents,BMAs）对实体瘤骨转移癌症或多发性骨髓瘤患者的不良反应（包括总不良反应、颌骨坏死、肾功能损伤和低钙血症）发生率。方法：由两名研究员按照检索策略独立检索PubMed、Cochrane Library、Embase、Clinical Trials、Web of science、中国知网（Zhi.com）、万方数据库（Wanfang）及维普数据库（Wipu）中骨改良药物治疗实体瘤骨转移癌症或多发性骨髓瘤患者的随机对照试验（randomized controlled trial, RCT），检索时限为建库至2024年11月。并对不同用药频率（标准给药组和长间隔给药组）的不良事件结局进行亚组分析。利用R4.3.3软件和STATA17.0进行贝叶斯网状Meta分析。结果：共纳入48项RCT，包含25 489例患者，涉及11种干预措施。总不良反应发生率方面，累积排序概率（surface under the cumulative ranking probabilities,SUCRA）显示氯膦酸标准给药组的不良反应发生率最高。在颌骨坏死发生率方面，SUCRA显示地舒单抗生物类似药标准给药组的不良反应发生率最高，但与原研药相比差异无统计学意义（P>0.05）。肾功能损伤发生率方面，SUCRA显示唑来膦酸标准给药组的不良反应发生率最高。低钙血症发生率方面，SUCRA显示利赛膦酸标准给药组的不良反应发生率最高，但与排名第二的地舒单抗原研药标准给药组相比差异无统计学意义（P>0.05）。亚组分析显示，标准给药组与长间隔给药组相比，肾功能损伤发生率明显升高（P<0.05）。结论：当前证据显示，不同骨改良药物具有自身特异的不良反应。其中，由于纳入亚组分析的研究数量较少导致存在患者健康状况、合并用药情况和个体差异等问题。因此，延长BMAs给药频率可能在某些情况下能够降低肾功能损伤发生率，但需更多的RCTs进行验证。
Abstract：Objective: To compare the incidence of adverse reactions [including total adverse reactions, osteonecrosis of the jaw(ONJ), renal impairment, and hypocalcemia] among patients with solid tumors bone metastasis or multiple myeloma treated with different bone-modifying agents,based on a network meta-analysis. Methods: Two researchers independently searched PubMed, Cochrane Library, Embase, Clinical Trials, Web of Science, CNKI, Wanfang, and Wipu for randomized controlled trials(RCTs) of bone-modifying agents for the treatment of patients with solid tumors with bone-metastatic cancers or multiple myeloma in accordance with the search strategy. Randomized controlled trials of patients with solid tumors bone metastatic cancer or multiple myeloma were searched from the establishment of the databases to November 2024, and different dosing frequencies(standardized) were examined. Adverse event outcomes were analyzed in subgroups with different dosing frequencies(standard dosing group and long interval dosing group). Bayesian mesh meta-analysis was performed using R 4.3.3 software and STATA 17.0. Results: A total of 48 RCTs comprising 25 489 patients and involving 11 interventions were included. Regarding the incidence of total adverse reactions, the highest incidence of adverse effects was shown in the standard clodronate administration group, as surface under the cumulative ranking probabilities(SUCRA). Regarding the incidence of ONJ, SUCRA showed that the incidence of adverse reactions was highest in the standard dosing group of denosumab biosimilar, but the difference was not statistically significant compared to that of the original drug(P>0.05). Regarding the incidence of renal impairment, SUCRA showed the highest incidence of adverse reactions in the zoledronic acid standard dosing group. Regarding the incidence of hypocalcemia, SUCRA showed the highest incidence of adverse reactions in the risedronic acid standard dosing group, but the difference was not statistically significant compared to the second-ranked standard dosing group of the denosumab prodrug(P>0.05). Subgroup analysis showed a significantly higher incidence of renal impairment in the standard dosing group compared with the long interval dosing group(P<0.05). Conclusion: Current evidence suggests that different bone-modifying drugs have their own specific adverse effects. Among them, due to the small number of studies included in subgroup analysis, there are problems such as patient health status, drug combination, and individual differences. Therefore, prolonging the frequency of BMAs administration may reduce the incidence of renal impairment in some cases, but more RCT trials are needed to confirm this.
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基本信息:
DOI：10.13210/j.cnki.jhmu.20241226.002
中图分类号:R733.3;G353.1
引用信息:
[1]胡玉婷,严颖,祁力文,等.不同骨改良药物治疗实体瘤骨转移或多发性骨髓瘤患者的安全性的网状Meta分析[J].海南医科大学学报,2025,31(05):373-386.DOI:10.13210/j.cnki.jhmu.20241226.002.
基金信息:
石河子大学医学院第一附属医院院级课题临床-基础研究项目（LJ202202）~~
2024-12-30
2024-12-30
2024-12-30