来氟米特和艾拉莫德分别联合甲氨蝶呤治疗类风湿关节炎的系统评价和药物经济性分析

doi:10.3969/j.issn.1004-583X.2024.04.002

摘要/Abstract

摘要：

目的探讨来氟米特和艾拉莫德分别联合甲氨蝶呤治疗类风湿关节炎(rheumatoid arthritis,RA)的有效性和药物经济学,为临床药物的合理选择提供参考。方法计算机搜索Pubmed、Medline、知网、万方、维普等数据库,查找来氟米特和艾拉莫德分别联合甲氨蝶呤治疗RA的随机对照试验,查询期限从建库到2023年7月。通过RevMan5.4软件对纳入文献进行meta分析,同时利用TreeAge Pro 2019 软件构建决策树模型,对2种药物分别联合甲氨蝶呤治疗RA进行成本-效果分析,并进行敏感性评价。结果 Meta分析结果显示,来氟米特联合甲氨蝶呤组治疗RA有效率高于甲氨蝶呤组[OR=2.95,95%CI(1.91-4.56),P<0.01],艾拉莫德联合甲氨蝶呤组治疗RA有效率高于甲氨蝶呤组[OR=3.35,95%CI(1.88-5.97),P<0.01];药物经济性分析发现,艾拉莫德联合甲氨蝶呤组对比来氟米特联合甲氨蝶呤组的增量成本-效果比为196 312.5元,即艾拉莫德联合甲氨蝶呤组每增加1例治疗有效较来氟米特联合甲氨蝶呤组需额外花费196 312.5元。敏感性分析结果:对研究结果影响最大的是艾拉莫德联合甲氨蝶呤组治疗有效率和来氟米特联合甲氨蝶呤组治疗有效率。结论来氟米特和艾拉莫德分别联合甲氨蝶呤治疗RA的有效性均高于甲氨蝶呤单独治疗,来氟米特联合甲氨蝶呤治疗更具有经济学优势。

关键词: 类风湿关节炎, 来氟米特, 艾拉莫德, 甲氨蝶呤, 成本-效果, 药物经济学

Abstract:

Objective To investigate the efficacy and pharmacoeconomics of leflunomide plus methotrexate versus iguratimod plus methotrexate in the treatment of rheumatoid arthritis (RA), and to provide reference for the rational selection of clinical drugs. Methods The randomized controlled trials about leflunomide plus methotrexate versus iguratimod plus methotrexate for RA were retrieved from Pubmed, Medline, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP from the establishment of the databases to July 2023. Meta-analysis was performed on the included literature by RevMan5.4 software. Ultimately, TreeAge Pro 2019 software was used to construct a decision tree model for cost-effectiveness analysis of leflunomide plus methotrexate versus iguratimod plus methotrexate for RA, and the sensitivity evaluation was assessed. Results The Meta-analysis showed the efficacy of leflunomide plus methotrexate or iguratimod plus methotrexate for RA was significantly higher than that of methotrexate alone (OR =2.95, 95%CI [1.91-4.56], P<0.01; OR =3.35, 95%CI [1.88-5.97], P<0.01; respectively). The incremental cost-effectiveness ratio(ICER) indicated that for each unit of increase in effectiveness of iguratimod plus methotrexate versus leflunomide plus methotrexate for RA, would lead to an increase the cost by 196, 312.5 RMB. The most influential factor on ICER was the treatment efficiency of iguratimod plus methotrexate or leflunomide plus methotrexate. Conclusion The efficacy of leflunomide plus methotrexate or iguratimod plus methotrexate is higher than that of methotrexate alone. Leflunomide plus methotrexate in the treatment of RA has economic advantages.

Key words: rheumatoid arthritis, leflunomide, iguratimod, methotrexate, cost-effectiveness, pharmacoeconomics

中图分类号:

R593.2

朱素华, 徐圣秋. 来氟米特和艾拉莫德分别联合甲氨蝶呤治疗类风湿关节炎的系统评价和药物经济性分析[J]. 临床荟萃, 2024, 39(4): 304-313.

Zhu Suhua, Xu Shengqiu. Review: efficacy and pharmacogenomics of leflunomide plus methotrexate versus iguratimod plus methotrexate in the treatment of rheumatoid arthritis[J]. Clinical Focus, 2024, 39(4): 304-313.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2024.04.002

https://huicui.hebmu.edu.cn/CN/Y2024/V39/I4/304

图/表 23

表1 敏感性分析参数设定

Tab.1 Parameter setting of sensitivity analysis

参数	最小值	基础值	最大值	分布
来氟米特成本(元)	688.32	860.40	1 032.48	Gamma
甲氨蝶呤成本(元)	86.40	108.00	129.60	Gamma
艾拉莫德成本(元)	3 703.68	4 629.60	5 123.52	Gamma
来氟米特联合甲氨蝶呤组效果参数(%)	85.44	89.94	94.45	Beta
艾拉莫德联合甲氨蝶呤组效果参数(%)	87.28	91.86	96.45	Beta

表2 纳入研究的基本特征

Tab.2 Basic characteristics of the included studies

纳入研究	组别	干预措施	例数	平均年龄(岁)	性别(例)
纳入研究	组别	干预措施	例数	平均年龄(岁)	男	女
冯要菊2013^[8]	对照组	甲氨蝶呤	46	54.20±3.90	10	36
	试验组	来氟米特20 mg 1/日+对照	46	54.00±4.10	8	38
陈华2018^[9]	对照组	甲氨蝶呤	45	59.20±3.30	31	14
	试验组	来氟米特20 mg 1/日+对照	45	58.90±3.10	29	16
杨茹2018^[10]	对照组	甲氨蝶呤	35	58.60±3.10	14	21
	试验组	来氟米特20 mg 1/日+对照	35	58.90±3.30	16	19
蔡艳 2018^[11]	对照组	甲氨蝶呤	84	38.52±10.08	48	36
	试验组	来氟米特20 mg 1/日+对照	84	37.68±10.02	41	43
钟燕玲2018^[12]	对照组	甲氨蝶呤	46	46.30±5.40	21	25
	试验组	来氟米特20 mg 1/日+对照	46	47.20±5.30	22	24
李艳琴 2020^[13]	对照组	甲氨蝶呤	55	46.10±5.36	23	32
	试验组	来氟米特20 mg 1/日+对照	55	45.25±5.02	25	30
孟岩 2017^[14]	对照组	甲氨蝶呤	60	64.31±8.22	25	35
	试验组	艾拉莫德25 mg 2/日+对照	60	64.83±9.41	28	32
任艳红2017^[15]	对照组	甲氨蝶呤	41	47.20±4.80	22	19
	试验组	艾拉莫德25 mg 2/日+对照	41	46.10±4.40	21	20
莫守崎2018^[16]	对照组	甲氨蝶呤	30	57.10±11.92	14	16
	试验组	艾拉莫德25 mg 2/日+对照	30	44.40±11.20	13	17
王隆辉2019^[17]	对照组	甲氨蝶呤	46	46.83±6.37	23	23
	试验组	艾拉莫德25 mg 2/日+对照	47	48.13±6.40	22	25
Duan 2015^[18]	对照组	甲氨蝶呤	30	48.40±10.20	10	20
	试验组	艾拉莫德25 mg 2/日+对照	30	48.90±12.20	8	22
孙佩翠 2022^[19]	对照组	甲氨蝶呤	43	48.96±5.24	26	17
	试验组	艾拉莫德25 mg 2/日+对照	43	49.05±4.32	24	19

图1 偏倚风险图

Fig.1 Bias risk map

图2 偏倚风险评价图

Fig.2 Evaluation map for bias risk

图3 来氟米特联合甲氨蝶呤组对比甲氨蝶呤组治疗RA有效率的森林图

Fig.3 Forest plot of effective rate of leflunomide plus methotrexate versus methotrexate for RA

图4 艾拉莫德联合甲氨蝶呤组对比甲氨蝶呤组治疗RA有效率的森林图

Fig.4 Forest plot of effective rate of iguratimod plus methotrexate versus methotrexate for RA

图5 来氟米特联合甲氨蝶呤组对比甲氨蝶呤组CRP水平的森林图

Fig.5 Forest plot of CRP level of leflunomide plus methotrexate versus methotrexate for RA

图6 艾拉莫德联合甲氨蝶呤组对比甲氨蝶呤组CRP水平的森林图

Fig.6 Forest plot of CRP level of iguratimod plus methotrexate versus methotrexate for RA

图7 来氟米特联合甲氨蝶呤组对比甲氨蝶呤组 ESR水平的森林图

Fig.7 Forest plot of ESR level of leflunomide plus methotrexate versus methotrexate

图8 艾拉莫德联合甲氨蝶呤组对比甲氨蝶呤组 ESR水平的森林图

Fig.8 Forest plot of ESR level of iguratimod plus methotrexate versus methotrexate

图9 来氟米特联合甲氨蝶呤组对比甲氨蝶呤组 RF的森林图

Fig.9 Forest plot of RF level of leflunomide plus methotrexate versus methotrexate

图10 艾拉莫德联合甲氨蝶呤组对比甲氨蝶呤组 RF的森林图

Fig.10 Forest plot of RF level of iguratimod plus methotrexate versus methotrexate

图11 来氟米特联合甲氨蝶呤组对比甲氨蝶呤组关节压痛的森林图

Fig.11 Forest plot of joint tenderness of leflunomide plus methotrexate versus methotrexate

图12 艾拉莫德联合甲氨蝶呤组对比甲氨蝶呤组关节压痛的森林图

Fig.12 Forest plot of joint tenderness of iguratimod plus methotrexate versus methotrexate

图13 来氟米特联合甲氨蝶呤组对比甲氨蝶呤组关节肿胀数的森林图

Fig.13 Forest plot of the number of joint swelling in leflunomide plus methotrexate versus methotrexate

图14 艾拉莫德联合甲氨蝶呤组对比甲氨蝶呤组关节肿胀数的森林图

Fig.14 Forest plot of the number of joint swelling in iguratimod plus methotrexate versus methotrexate

图15 来氟米特联合甲氨蝶呤组对比甲氨蝶呤组晨僵时间的森林图

Fig.15 Forest plot of morning stiffness time of leflunomide plus methotrexate versus methotrexate

图16 艾拉莫德联合甲氨蝶呤组对比甲氨蝶呤组晨僵时间的森林图

Fig.16 Forest plot of morning stiffness time in iguratimod plus methotrexate versus methotrexate

图17 来氟米特联合甲氨蝶呤组对比甲氨蝶呤组不良反应发生率的森林图

Fig.17 Forest plot of the incidence of adverse reactions in leflunomide plus methotrexate versus methotrexate

图18 艾拉莫德联合甲氨蝶呤组对比甲氨蝶呤组不良反应发生率的森林图

Fig.18 Forest plot of the incidence of adverse reactions in iguratimod plus methotrexate versus methotrexate

图19 来氟米特和艾拉莫德的决策树模型注:plfmt:来氟米特联合甲氨蝶呤组治疗有效率;clfmt:来氟米特治疗成本;cjadl:甲氨蝶呤治疗成本;palmd为:艾拉莫德联合甲氨蝶呤组治疗有效率;calmd:艾拉莫德治疗成本

Fig.19 The decision tree model of leflunomide versus iguratimod Note: plfmt: the treatment efficiency rate of leflunomide plus methotrexate; clfmt: the cost of leflunomide treatment; cjadl: the cost of methotrexate treatment; palmd: the treatment efficiency rate of iguratimod plus methotrexate; calmd: the cost of iguratimod treatment

表3 艾拉莫德对比来氟米特治疗RA的成本-效果分析

Tab.3 Cost-effectiveness analysis of iguratimod versus leflunomide in the treatment of RA

组别	成本/元	效果/%	增量成本/元	增量效果/%	ICER(元/例有效)
来氟米特联合甲氨蝶呤组	968.4	89.94	-	-	-
艾拉莫德联合甲氨蝶呤组	4 737.6	91.86	3 769.2	1.92	196 312.5

图20 飓风图注:plfmt:来氟米特联合甲氨蝶呤组治疗有效率;clfmt:来氟米特治疗成本;cjadl:甲氨蝶呤治疗成本;palmd为:艾拉莫德联合甲氨蝶呤组治疗有效率;calmd:艾拉莫德治疗成本

Fig.20 Hurricane chart Note: plfmt: the treatment efficiency rate of leflunomide plus methotrexate; clfmt: the cost of leflunomide treatment; cjadl: the cost of methotrexate treatment; palmd: the treatment efficiency rate of iguratimod plus methotrexate; calmd: the cost of iguratimod treatment

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