Review: efficacy and pharmacogenomics of leflunomide plus methotrexate versus iguratimod plus methotrexate in the treatment of rheumatoid arthritis

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

Abstract

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

CLC Number:

R593.2

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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URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2024.04.002

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

Figures/Tables 23

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

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

Fig.1 Bias risk map

Fig.2 Evaluation map for bias risk

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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