Study selection

Through a preliminary search, 3,245 relevant articles were obtained, and 562 duplicate articles were excluded. After reading the title and abstract, 24 articles were included, and 11 articles were included through full-text screening (3 studies of the same RCT repeatedly published with different outcomes or populations, 2 studies with no interest outcome indicators, and 6 conference abstracts without peer review). Finally, 13 studies were included [11,12,13,14,15,16,17,18,19,20,21,22,23]. The literature screening process is illustrated in Fig. 1.

Fig. 1

Literature screening process

Study characteristics

Thirteen studies were included in this analysis, involving a total of 3,622 patients, and the authors of the included studies were from the United States, the United Kingdom, Germany, Australia, and Switzerland. The year of publication was between 2016 and 2023, and most of the studies were published in recent three years. The diagnosis criteria for SLE were mainly the American College of Rheumatology classification criteria [24, 25]. Eleven studies [11,12,13,14,15,16,17,18,19, 21,22,23] were multi-arm studies on a targeted small-molecule drug at different doses. Targeted small-molecule drugs used in the intervention group included JAKs (Baricitinib Filgotinib, Deucravacitinib, GSK2586184), BTK (Fenebrutinib, Evobrutinib), Cereblon (Iberdomide), SYK (Lanraplenib), and S1PR1 (Cenerimod). The basic characteristics of included studies are provided in Table 1.

Table 1 Basic characteristics of the original studies included in this systematic reviewRisk of bias in the included studies

In terms of randomization methods, the computer-generated random sequence method was used in 4 studies [11, 14, 17, 18], and the inter-active web response system was used in 3 studies [19, 21, 22]. Allocation concealment was used in 4 studies [11, 14, 17, 18]. The blinding method was used in all studies. Data from all studies were complete, and no selective reporting was found. The sample size of 2 studies [13, 21] was small, which may cause publication bias. Figures 2 and 3 show the results of the risk of bias for each included study.

Fig. 2

Risk of bias graph of all included studies

Fig. 3

Risk of bias summary of all included studies

Meta-analysisSRI-4 response The correlation among intervention measures

SRI-4 response was reported in 7 studies [12, 14, 16,17,18,19, 23], involving 5 targeted small-molecule drugs from JAKs, BTK, and Cereblon. The comparison between targeted small-molecule drugs and the placebo was only reported in each study, and there was no pairwise comparison among targeted small-molecule drugs. The number of studies on direct comparison between Baricitinib and the placebo was the largest, and there was no closed loop, as shown in Fig. 4. (JAKs: red; BTK: khaki; Cereblon: green; SYK: yellow; S1PR1:purple; Placebo: blue).

Fig. 4

Network diagram of targeted drug therapy in the treatment of SLE using SRI-4 as the outcome indicator

Synthesized results

Network meta-analysis results showed that 3 targeted small-molecule drugs (Baricitinib, Deucravacitinib, and Iberdomideb) were significantly superior to the placebo in improving SRI-4 response (P < 0.05) (Fig. 5). There were differences in efficacy among some targeted small-molecule drugs. The effect of Deucravacitinib was significantly superior to that of Baricitinib (RR = 1.32, 95% CI (1.04, 1.68), P < 0.05) (Table 2). The top three drugs in the SUCRA ranking were Deucravacitinib (0.91), Iberdomideb (0.79), and Fenebrutinib (0.45) (Table 3).

Table 2 League table of SRI-4 response of targeted small-molecule drug therapyTable 3 Probability and ranking of Bayesian network meta-analysis of primary outcome indicators of each targeted small-molecule drugFig. 5

Forest plot of meta-analysis of SRI-4 response of targeted small-molecule drug therapy compared with placebo

Meta-regression

Because different doses of targeted small-molecule drugs and various courses of treatment were adopted in the included studies, meta-regression was performed on the dose and the course of treatment to discuss the effect of the dose and the course of treatment on SRI-4 response. The results showed that the efficacy and safety of targeted small-molecule drugs were not significantly correlated with the dose and the course of treatment as compared to the placebo, and the results were not statistically significant (Table 4).

Table 4 Meta-regression results of primary outcome indicators of each targeted small-molecule drugBICLA response The correlation among each intervention measure

BICLA response was reported in 5 studies [12, 14, 17, 19, 23], involving 3 targeted small-molecule drugs from JAKs and BTK. The comparison between targeted small-molecule drugs and the placebo was only reported in each study, and there was no pairwise comparison among targeted small-molecule drugs. The number of studies directly comparing Baricitinib and the placebo was the greatest, and there was no closed loop, as shown in Fig. 6.

Fig. 6

Network diagram of targeted drug therapy in the treatment of SLE using BICLA response as the outcome indicator

Synthesized results

Deucravacitinib significantly outperformed the placebo in improving BICLA response (RR = 1.55, 95% CI (1.20, 2.02), P < 0.05) (Fig. 7). There were differences in the efficacy among some targeted small-molecule drugs. Deucravacitinib was more effective than Baricitinib (RR = 1.47, 95% CI (1.11, 1.94), P < 0.05) (see Table 5). The top three drugs in the SUCRA ranking were Deucravacitinib (0.98), Fenebrutinib (0.56), and Baricitinib, in sequence (0.40) (Table 3).

Table 5 League table of BICLA stable response of targeted small-molecule drug therapyFig. 7

Forest plot of meta-analysis of BICLA response of targeted small-molecule drug therapy compared with placebo

Meta-regression

Due to differences in the dose of targeted small-molecule drugs and the course of treatment in the included studies, meta-regression was performed on the dose and the course of treatment to explore the effect of the dose and the course of treatment on BICLA response. The results showed that the efficacy and safety of targeted small-molecule drugs were not significantly correlated with the dose and the course of treatment as compared to the placebo, and the results were not statistically significant (Table 4).

Adverse reactions The correlation among each intervention measure

Adverse reactions were reported in 11 studies [12,13,14, 16,17,18,19,20,21,22,23], involving 9 targeted small-molecule drugs from JAKs, BTK, SYK, Cereblon, and S1PR1. There was one closed loop (Filgotinib-Lanraplenib-Placebo). The studies directly comparing Iberdomide and the placebo were the largest in number, as shown in Fig. 8.

Fig. 8

Network diagram of targeted drug therapy in the treatment of SLE using adverse reaction as the outcome indicator

Synthesized results

There were no statistically significant differences in the adverse reactions between targeted small-molecule drugs and the placebo. The safety profile of Iberdomide was significantly lower than that of placebo (RR = 1.21, 95% CI (1.07, 1.37), P < 0.05)(Fig. 9). There were differences in the adverse reactions among some targeted small-molecule drugs. Baricitinib (RR = 0.84, 95% CI (0.73, 0.95), P < 0.05), Cenerimod (RR = 0.60, 95% CI (0.39, 0.89), P < 0.05), Deucravacitinib (RR = 0.84, 95% CI (0.73, 0.96), P < 0.05), and Evobrutinib (RR = 0.87, 95% CI (0.75, 0.99), P < 0.05) had fewer adverse reactions in comparison with Iberdomide (Table 6). The top three drugs in the SUCRA ranking were Cenerimod (0.93), Filgotinib (0.73), and Placebo (0.66), in order (Table 3).

Table 6 League table of adverse reaction of targeted small-molecule drug therapyFig. 9

Forest plot of meta-analysis of adverse reaction of targeted small-molecule drug therapy compared with placebo

Meta-regression

Owing to the differences in the dose of targeted small-molecule drugs and the course of treatment, meta-regression was performed on the dose and the course of treatment to investigate the effect of the dose and the course of treatment on adverse reactions. The results showed that the safety of targeted small-molecule drugs was not significantly correlated with the dose and the course of treatment as compared to the placebo, and the results were not statistically significant (Table 4).

Secondary outcome indicators

Our study showed that in terms of CLASI-50, Deucravacitinib was significantly superior to the placebo (P < 0.05). Deucravacitinib was more significantly effective than Fenebrutinib. Deucravacitinib was more significantly effective than Iberdomide. In terms of tender joint count, Baricitinib and Deucravacitinib were significantly superior to the placebo (P < 0.05), and there was no significant difference in the efficacy among all targeted small-molecule drugs. No significant differences were observed in swollen joint count between all targeted small-molecule drugs and the placebo, or among targeted small-molecule drugs. The detailed analysis results are shown in Appendix 2.