吗替麦考酚酯联合来氟米特或他克莫司诱导治疗狼疮肾炎的疗效及安全性比较

邵慧君; 冉宸宇; 吴月; 刘群; 马艳; 陶金辉

doi:10.16462/j.cnki.zhjbkz.2024.09.018

吗替麦考酚酯联合来氟米特或他克莫司诱导治疗狼疮肾炎的疗效及安全性比较

doi: 10.16462/j.cnki.zhjbkz.2024.09.018

邵慧君¹,
冉宸宇²,
吴月¹,
刘群²,
马艳¹,
陶金辉^{1, 2, ,}

1.
中国科学技术大学附属第一医院变态反应与临床免疫科，合肥 230001
2.
皖南医学院临床医学院，芜湖 241002

基金项目:

中央高校基本科研业务费专项资金资助 YD9110002017

详细信息

通讯作者:
陶金辉，E-mail: taojinhui@ustc.edu.cn

中图分类号: R593.24+2
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- 被引次数: 0
出版历程
- 收稿日期: 2024-01-29
- 修回日期: 2024-05-16
- 网络出版日期: 2024-10-24
- 刊出日期: 2024-09-10

Comparison of the efficacy and safety of mycophenolate mofetil combined with leflunomide or tacrolimus induction in the treatment of lupus nephritis

SHAO Huijun¹,
RAN Chenyu²,
WU Yue¹,
LIU Qun²,
MA Yan¹,
TAO Jinhui^{1, 2
, ,}

1.
Department of Allergy and Clinical Immunity, The First Affiliated Hospital of the University of Science and Technology of China, Hefei 230001, China
2.
School of Clinical Medicine, Wannan Medical College, Wuhu 241002, China

Funds:

Fundamental Research Funds for the Central Universities YD9110002017

More Information

Corresponding author: TAO Jinhui, E-mail: taojinhui@ustc.edu.cn

摘要

摘要: 目的评估吗替麦考酚酯(mycophenolate mofetil, MMF)联合来氟米特(leflunomide, LEF)或他克莫司(tacrolimus, TAC)诱导治疗狼疮肾炎(lupus nephritis, LN)的疗效和安全性。方法从单用MMF或环磷酰胺(cyclophosphamide, CYC)治疗无效的LN患者中筛选出改用MMF(1 g/d)联合LEF(20 mg/d)或TAC(2 mg/d)治疗的患者，分析两组间缓解达标率、实验室指标及不良反应差异。结果共纳入LN患者278例，从中筛选出38例并分为MMF+LEF组和MMF+TAC组，每组各19例，分析两组患者治疗情况结果显示：(1)治疗LN缓解达标中，治疗3个月时MMF+LEF组有7例(36.84%)，MMF+TAC组有10例(52.63%)；治疗6个月时MMF+LEF组有10例(52.63%)，MMF+TAC组有14例(73.68%)；治疗3个月、6个月两组间的达标率差异均无统计学意义(均P＞0.05)；(2)治疗6个月后，两组补体成分3(component 3, C3)、补体成分4(component 4, C4)、尿素氮、白蛋白、免疫球蛋白(immunoglobulin, Ig)A、IgM、尿总蛋白/尿液肌酐前后比较差异均有统计学意义(均P＜0.05)；治疗3个月、6个月时两组间差异均无统计学意义(均P＞0.05)；(3)两组不良反应差异无统计学意义(P＞0.05)。结论 MMF联合LEF和联合TAC均可改善LN病情，两者缓解达标率和安全性无明显差异。
- 系统性红斑狼疮 /
- 狼疮肾炎 /
- 吗替麦考酚酯 /
- 来氟米特 /
- 他克莫司
Abstract: Objective To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in combination with either leflunomide (LEF) or tacrolimus (TAC) as induction therapy for lupus nephritis (LN). Methods Patients with refractory LN who did not respond to monotherapy with MMF or cyclophosphamide (CYC) were selected for switching to combination therapy with MMF (1 g/d) plus either LEF (20 mg/d) or TAC (2 mg/d). The remission rates, laboratory parameters, and adverse reactions were compared between the two groups. Results A total of 278 patients with LN were included, and 38 patients (19 in each group) were selected for analysis. The results showed that: (1) In terms of achieving remission in LN, at 3 months, there were 7 cases (36.84%) in the MMF+LEF group and 10 cases (52.63%) in the MMF+TAC group; at 6 months, there were 10 cases (52.63%) in the MMF+LEF group and 14 cases (73.68%) in the MMF+TAC group. However, the differences in remission rates between the two groups at 3 months and 6 months were not statistically significant (all P>0.05). (2) After 6 months of treatment, there were statistically significant differences in complement C3, C4, blood urea nitrogen, albumin, IgA, IgM, and urine total protein/creatinine ratio between the two groups (all P < 0.05). However, there were no statistically significant differences between the two groups at 3 months and 6 months (all P>0.05). (3) There were no significant differences in adverse reactions between the two groups (P>0.05). Conclusions Both the combination of MMF and LEF, as well as the combination of MMF and TAC, significantly improved the condition of LN. There were no significant differences in remission rates and safety between the two combinations.
- Systemic lupus erythematosus /
- Lupus nephritis /
- Mycophenolate mofetil /
- Leflunomide /
- Tacrolimus

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表 1 两组间治疗3个月、6个月后疗效比较

Table 1. Comparison of efficacy between the two groups at 3 and 6 months after treatment

随访时间 Follow time	结果 Result	MMF+LEF组 group ^① (n=19)	MMF+TAC组 group ^① (n=19)	Z/χ²值 value	P值 value
治疗3个月 Treatment for 3 months	未缓解 Unresolved	12(63.16)	9(47.37)	0.711	0.399
	部分缓解 Partial relief	2(10.53)	5(26.32)	1.170	0.242
	完全缓解 Complete remission	5(26.32)	5(26.32)	0.000	1.000
	总缓解率 Total relief rate	7(36.84)	10(52.63)	1.714	0.424
治疗6个月 Treatment for 6 months	未缓解 Unresolved	9(47.37)	5(26.32)	1.089	0.297
	部分缓解 Partial relief	4(21.05)	6(31.58)	1.243	0.214
	完全缓解 Complete remission	6(31.58)	8(42.11)	0.222	0.638
	总缓解率 Total relief rate	10(52.63)	14(73.68)	1.829	0.401
注：MMF，吗替麦考酚酯；LEF，来氟米特；TAC，他克莫司。 ①以人数(占比/%)表示。 Note: MMF, mycophenolate mofeti; LEF, leflunomide; TAC, tacrolimus. ① Number of people(proportion/%).

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表 2 两组间实验室指标比较

Table 2. Comparison of laboratory indicators between the two groups

类别 Category	基线 Baseline		治疗3个月 Treatment for 3 months
类别 Category	MMF+LEF组 group (n=19)^①	MMF+TAC组 group (n=19)^①	MMF+LEF组 group (n=19)^①			MMF+TAC组 group (n=19)^①
尿素氮 Urea nitrogen/(mmol·L^-1)	59.37±17.52	59.11±19.61	60.07±18.89			63.11±20.53
白蛋白 Albumin/(g·L^-1)	35.86±7.76	38.16±4.99	37.56±7.72			37.78±9.63
肌酐 Creatinine/(μmol·L^-1)	59.37±17.52	59.11±19.61	60.07±18.89			63.11±20.53
尿液总蛋白·尿液肌酐^-1 Urine total protein·urine creatinine^-1/(g·g^-1)	2.27(0.94, 4.17)	1.87(0.93, 2.48)	0.85(0.44, 2.20)			0.98(0.37, 2.43)
eGFR/(ml·min^-1·1.73m^-2)	108.84±22.53	117.59±23.19	107.94±21.44			113.91±23.53
补体C3 Complement C3/(g·L^-1)	0.95±0.37	0.79±0.20	1.01±0.25			0.81±0.19
补体C4 Complement C4/(g·L^-1)	0.21±0.10	0.17±0.08	0.23±0.07			0.19±0.09
免疫球蛋白A Immunoglobulin A/(g·L^-1)	2.07(1.66, 2.39)	2.11(1.24, 3.14)	1.86(1.29, 2.19)			1.86(1.31, 2.94)
免疫球蛋白G Immunoglobulin G/(g·L^-1)	9.06±3.99	9.59±2.19	8.36±3.55			9.98±2.24
免疫球蛋白M Immunoglobulin M/(g·L^-1)	0.90±0.60	0.96±0.55	0.79±0.58			0.96±0.55

类别 Category	治疗6个月 Treatment for 6 months		组间 Between-group		组内 Within-group		交互 Interaction
类别 Category	MMF+LEF组 group (n=19)^①	MMF+TAC组 group (n=19)^①	F值 value	P值 value	F值 value	P值 value	F值 value	P值 value
尿素氮 Urea nitrogen/(mmol·L^-1)	57.06±11.81	61.58±21.63	0.117	0.734	5.607	0.005	0.902	0.410
白蛋白 Albumin/(g·L^-1)	37.87±7.40	39.97±4.58	0.589	0.448	1.745	0.042	0.610	0.505
肌酐 Creatinine/(μmol·L^-1)	57.06±11.81	61.58±21.63	0.178	0.675	1.440	0.244	1.219	0.301
尿液总蛋白·尿液肌酐^-1 Urine total protein·urine creatinine^-1/(g·g^-1)	0.95(0.40, 1.51)	0.55(0.24, 1.40)	0.463	0.631	18.203	＜0.01	0.728	0.399
eGFR/(ml·min^-1·1.73m^-2)	113.12±13.89	115.95±24.41	0.841	0.365	1.565	0.216	0.914	0.405
补体C3 Complement C3/(g·L^-1)	1.03±0.27	9.96±2.55	5.371	0.141	2.169	0.026	0.442	0.566
补体C4 Complement C4/(g·L^-1)	0.22±0.07	0.21±0.15	1.290	0.264	1.933	0.044	0.442	0.586
免疫球蛋白A Immunoglobulin A/(g·L^-1)	1.8(1.34, 2.58)	1.77(1.29, 2.79)	0.452	0.506	4.449	0.015	1.181	0.301
免疫球蛋白G Immunoglobulin G/(g·L^-1)	8.72±3.06	9.96±2.55	1.504	0.228	0.225	0.764	1.995	0.151
免疫球蛋白M Immunoglobulin M/(g·L^-1)	0.72±0.45	0.94±0.49	0.795	0.378	4.624	0.013	3.28	0.043
注：MMF，吗替麦考酚酯；LEF，来氟米特；TAC，他克莫司；eGFR，估算的肾小球滤过率；C3, 成分3; C4, 成分4。 ①以x±s或M(P₂₅, P₇₅)表示。 Note: MMF, mycophenolate mofetil; LEF, leflunomide; TAC, tacrolimus; eGFR, estimated glomerular filtration rate; C3, component 3; C4, component 4. ① x±s or M(P₂₅, P₇₅).

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表 3 两组间不良事件发生率和复发率比较

Table 3. Comparison of the incidence of adverse events and recurrence rates between the two groups

项目 Project	MMF+LEF组 group ^① (n=19)	MMF+TAC组 group ^① (n=19)	P值 value
感染 Infection	3(15.80)	2(10.50)	1.000^②
尿路感染 Urinary tract infection	2(10.50)	1(5.30)	1.000^②
呼吸道感染 Respiratory tract infection	0(0)	1(5.30)	1.000^②
带状疱疹 Shingles	1(5.30)	2(10.50)	1.000^②
肝酶升高 Elevated liver enzymes	2(10.50)	1(5.30)	1.000^②
白细胞减少 Decreased white blood cells	2(10.50)	0(0.00)	0.486^②
疾病复发 Disease recurrence	2(10.50)	3(15.80)	1.000^②
注：MMF，吗替麦考酚酯；LEF，来氟米特；TAC，他克莫司。 ①以人数(占比/%)表示；②表示Fisher确切概率法。 Note: MMF, mycophenolate mofeti; LEF, leflunomide; TAC, tacrolimus. ① Number of people(proportion/%); ② Fisher′s exact probability method.

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