不同骨改良药物治疗实体瘤骨转移或多发性骨髓瘤患者疗效的网状Meta分析OA

Background Skeletal-related events(SREs)are severe complications in patients with bone metastases from solid tumors or multiple myeloma.Bone-modifying agents(BMAs)offer the advantage of a targeted drug delivery system to bone tissue compared to traditional treatment methods.However,given the variety of BMAs and the relative complexity of drug treatment strategies,determining the appropriate drug and dosing frequency is a significant challenge currently faced by BMAs.Objective A network meta-analysis comparing the efficacy of different BMAs in the treatment of patients with bone metastases from solid tumors or multiple myeloma.Methods Two researchers independently searched PubMed,Cochrane Library,Embase,Clinical Trials,Web of Science,China National Knowledge Infrastructure,Wanfang Data,and VIP databases for randomized controlled trials(RCTs)on bone-modifying agents in the treatment of patients with bone metastases from solid tumors or multiple myeloma,following the predefined search strategy.The search timeframe spanned from the inception of each database to January 2024.The quality of the included studies was assessed using the Cochrane risk of bias tool.Statistical analyses were performed using R 4.3.3 and STATA 17.0 software.Results A total of 64 RCTs were included,involving 28 773 patients.The interventions involved were:placebo/no bone-modifying agents group(PLA),standard dosing of denosumab originator group(DENO),standard dosing of zoledronic acid group(ZA),standard dosing of ibandronic acid group(IBA),standard dosing of pamidronate group(PAM),longer-interval dosing of pamidronate group(PAM*),standard dosing of clodronate group(CLO),standard dosing of risedronate group(RIS),standard dosing of alendronate group(ALE),standard dosing of denosumab biosimilar group(DENO#),longer-interval dosing of denosumab originator group(DENO*),and longer-interval dosing of zoledronic acid group(ZA*),totaling 12 different intervention measures.For the incidence of total SREs,the surface under the cumulative ranking curve(SUCRA)showed the following ranking:DENO(82.29%)>DENO*(81.48%)>DENO#(76.09%)>ZA(59.74%)>ZA*(55.53%)>IBA(43.19%)>PAM*(42.21%)>CLO(37.37%)>PAM(31.87%)>RIS(31.26%)>PLA(8.97%).For the time to first SREs,the SUCRA ranking was:DENO*(85.45%)>DENO(83.89%)>IBA(56.72%)>ZA(53.35%)>PAM(44.39%)>ZA*(42.58%)>DENO#(27.04%)>PLA(6.59%).Regarding overall survival(OS),the SUCRA ranking was:ZA*(79.66%)>IBA(79.05%)>DENO(73.19%)>ZA(64.14%)>CLO(42.96%)>PAM(30.55%)>PLA(18.95%)>RIS(11.49%).For progression-free survival(PFS),the SUCRA ranking was:ZA(75.90%)>ALE(68.08%)>PAM(53.91%)>PLA(31.73%)>CLO(20.37%).Subgroup analysis revealed there was no statistically significant differences between the standard dosing group and the extended-interval dosing group in overall incidence of SREs or the time to the first SREs(Overall incidence of SREs:RR=1.00,95%CI=0.89-1.13,P=0.960;The time to the first SREs:HR=0.97,95%CI=0.74-1.27,P=0.775).Conclusion Current evidence suggests that denosumab may be the best pharmacological intervention available for the treatment of patients with bone metastases from solid tumours or multiple myeloma.In this regard,extended dosing frequency may be an acceptable treatment regimen option.