Effectiveness and safety of tripterygium glycosides tablet (雷公藤多苷片) for lupus nephritis: a systematic review and Meta-analysis

doi:10.19852/j.cnki.jtcm.2022.05.001

Abstract

Abstract:

OBJECTIVE: To investigate the effectiveness and safety of tripterygium glycosides (TG) tablet (雷公藤多苷片) for the treatment of Lupus nephritis (LN).

METHODS: Several databases were systematically searched including PubMed, Embase, Cochrane, Wiley, China National Knowledge Infrastructure Database, SinoMed and Wanfang Library till June 20, 2020. Revman5.3 was utilized to analyze the data according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement.

RESULTS: In total, 8 randomized controlled trials involving 583 participants were identified. Meta-analyses showed that, compared with glucocorticoids (GC) alone, the combination with TG tablet provided a statistically significant improvement in total remission (TR) (RR = 1.27, 95% CI: 1.08-1.50, P = 0.004), complete remission (CR) (RR = 1.61, 95% CI: 1.05-2.47, P = 0.03) and C3 levels (WMD = 0.27, 95% CI: 0.14-0.39, P < 0.000 1), C4 levels (WMD = 0.12, 95% CI: 0.07-0.17, P < 0.000 01). No significant differences were seen in TR, CR, proteinuria, serum creatinine, C3 and C4 (TR: RR = 1.00, 95% CI: 0.87-1.16, P = 0.95; CR: RR = 1.10, 95% CI: 0.78-1.56, P = 0.58; proteinuria levels: WMD = -0.06, 95% CI: -0.13 to 0.01, P = 0.10; serum creatinine levels: WMD = -0.01, 95%CI: -7.36 to 7.35, P = 1.00; C3 levels: WMD = 0.01, 95%CI: -0.06 to 0.07, P = 0.84; C4 levels: WMD = -0.01, 95%CI: -0.03 to 0.01, P = 0.49) between azathioprine (AZA) / leflomit (LEF) + GC and TG tablet + GC. Adverse events (hepatic dysfunction, nausea, vomitting) showed no statistical differences between the TG tablet + GC group and the GC group. There were more new onset of irregular menstruation in the TG tablet + GC group than those in the AZA + GC (RR = 3.57, 95% CI: 1.40-9.11, P = 0.008) /LEF+ GC (RR = 6.69, 95% CI: 2.42-18.46, P = 0.000 2) group, but leucopenia lower than those in AZA + GC group (RR = 0.38, 95% CI: 0.17-0.85, P = 0.02) and alopecia (RR = 0.14, 95% CI: 0.03-0.77, P = 0.02) and rash (RR = 0.09, 95% CI: 0.01-0.69, P = 0.02) lower than those in LEF + GC group.

Conclusions: This review indicates that TG tablet maybe effective in LN treatment. Nevertheless, adverse events cannot be ignored. Large sample, multi-center, high-quality clinical studies are needed to verify the exact effects and safety of TG tablet in treatment of LN.

Key words: tripterygium glycosides, lupus nephritis, treatment outcome, safety, systematic review, Meta-analysis

ZHOU Yingyan, LIANG Huasheng, YAN Jingyao, HE Xiaohong, PAN Lili, LI Xue, CHEN Xianghong, CHEN Xiumin, YANG Aicheng, HUANG Qingchun. Effectiveness and safety of tripterygium glycosides tablet (雷公藤多苷片) for lupus nephritis: a systematic review and Meta-analysis[J]. Journal of Traditional Chinese Medicine, 2022, 42(5): 671-680.

Figures/Tables 9

Figure 1 Process of searching for and screening studies RCTs: randomized controlled trials.

Table 1 Characteristics of the included trials

Study	Number of patients		Sex ratio (M/F)		Age (years)		Intervention and dose		Duration	Outcome
Study	Experimental	Control	Experimental	Control	Experimental	Control	Experimental	Control	Duration	Outcome
Wang JJ et al 2015²³	40	44	2 /38	2/42	34.2±8.7	32.0±10.3	TG, 60 mg/d + GC, 10 mg/d	AZA, 2 mg·kg^-1·d^-1 + GC, 10 mg/d	24 months	CR, AEs
Shi F et al 2016²⁴	28	27	3/25	4/23	31.04±4.17	30.15±4.37	TG, 60 mg/d, 10 mg/d	AZA, 1.5-4 mg·kg^-1·d^-1	null	CR, PR, 24-hour urinary protein, C3, C4, Cr, AEs
Dai H, Liu W 2018²⁵	46	45	null	null	null	null	TG, 60 mg/d + GC, 5-10 mg/d	LEF, 20 mg/d + GC, 5-10 mg/d	6 months	CR, PR, 24-hour urinary protein, C3, Cr, SLEDAI, ALB, AEs
Hu XW et al 2008²⁶	61	61	5/56	1/60	31.5±8.1	27.8±8.2	TG, 60 mg/d + GC, 10 mg/d	LEF, 20 mg/d + GC, 10 mg/d	24 months	C3, C4, anti-dsDNA, AEs
Chen GW 2012²⁰	27	26	3/24	3/23	null	null	TG, 1-1.5 mg·kg^-1·d^-1, + GC 0.5 mg·kg^-1·d^-1	GC 1 mg·kg^-1·d^-1	6 months	CR, PR, 24-hour urinary protein, Cr
Hong L 2018²²	41	41	10/31	11/30	30.14±4. 67	30. 02±4. 71	TG, 1.5 mg·kg^-1·d^-1, + GC, 10 mg/d	GC, 10 mg/d	12 weeks	24-hour urinary protein, C3, C4, anti-dsDNA
Liu F et al 2018²¹	31	31	3/28	5/26	37.9±3.4	36.6±3.5	TG, 1.0 mg·kg^-1·d^-1, + GC, 1 mg·kg^-1·d^-1	GC, 1 mg·kg^-1·d^-1	8 weeks	CR, PR, 24-hour urinary protein, C3, Cr, SLEDAI, ALB, Cr, AEs
Du YL et al 2019²⁷	34	34	5/29	4/30	54.38±3.32	32.74±5.1	TG, 1-1.5 mg·kg^-1·d^-1, + GC 0.5 mg·kg^-1·d^-1	GC 1 mg·kg^-1·d^-1	6 months	CR, PR, AEs

Figure 2 Risk of bias graph and summary A: risk of bias graph: judgements about each risk of bias item presented as percentages across all included studies; B: risk of bias summary: judgements about each risk of bias item for each included study. “?”: unclear risk of bias; “+”: low risk of bias; “-”: high risk of bias

Figure 3 Results of the Meta-analysis of the efficacy of TG tablet combined with GC versus GC A: forest plot of comparison of TR; B. Forest plot of comparison of CR; C: forest plot of comparison of 24-hour urinary protein; D: forest plot of comparison of C3; E: forest plot of comparison of C4; F: forest plot of comparison of serum creatinine. TG: tripterygium glycosides tablet, GC: glucocorticoids, CR: complete remission, TR: total remission [total CR plus partial remission (PR)].

Figure 4 Results of the Meta-analysis of the efficacy of TG tablet combined with GC versus AZA/LEF combined with GC A: forest plot of comparison of TR; B: forest plot of comparison of CR; C: forest plot of comparison of 24-h urinary protein; D: forest plot of comparison of C3; E: forest plot of comparison of C4; F: forest plot of comparison of serum creatinine. TG: tripterygium glycosides tablet; GC: glucocorticoids; AZA: azathioprine; LEF: leflomit; CR: complete remission; TR: total remission [total CR plus partial remission (PR)].

Table 2 Meta-analysis of the safety of TG tablet in treatment of patients with lupus nephritis

Therapeutic regimen	Indicator	Number of studies	Q test, P value	Model selected	RR (95% CI)	P value
TG + GC vs GC	Nausea and vomitting	2	0.31	fixed	0.44 (0.14, 1.37)	0.16
TG + GC vs GC	Hepatic dysfunction	2	0.71	fixed	0.67 (0.12, 3.86)	0.65
TG vs AZA	Infection	2	0.74	fixed	1.11 (0.72, 1.72)	0.64
	Irregular menstruation	2	0.55	fixed	3.57 (1.40, 9.11)	0.008
	Leucopenia	2	0.40	fixed	0.38 (0.17, 0.85)	0.02
TG vs LEF	Infection	2	0.37	fixed	0.49 (0.15, 1.58)	0.23
	Irregular menstruation	2	0.49	fixed	6.69 (2.42, 18.46)	0.0002
	Leucopenia	2	0.62	fixed	0.50 (0.13, 1.93)	0.31
	Alopecia	2	0.23	fixed	0.14 (0.03, 0.77)	0.02
	hepatic dysfunction	2	0.46	fixed	0.69 (0.27, 1.75)	0.44
	rash	2	0.38	fixed	0.09 (0.01, 0.69)	0.02

Figure 5 Results of the Meta-analysis of the safety of TG tablet combined with GC versus GC A: forest plot of comparison of hepatic dysfunction; B: forest plot of comparison of nausea and vomitting. TG: tripterygium glycosides tablet, GC: glucocorticoids.

Figure 6 Results of the Meta-analysis of the safety of TG tablet combined with GC versus AZA combined with GC A: forest plot of comparison of infection; B: forest plot of comparison of irregular menstruation; C: forest plot of comparison of leucopenia. TG: tripterygium glycosides tablet; GC: glucocorticoids; AZA: azathioprine.

Figure 7 Results of the Meta-analysis of the safety of TG tablet combined with GC versus LEF combined with GC A: forest plot of comparison of infection; B: forest plot of comparison of irregular menstruation; C: forest plot of comparison of leucopenia; D: forest plot of comparison of alopecia; E: forest plot of comparison of hepatic dysfunction; F: forest plot of comparison of rash. TG: tripterygium glycosides tablet; GC: glucocorticoids; LEF: leflomit.

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