Efficacy and Safety of Biologics for Systemic Lupus Erythematosus (SLE): A Systematic Review and Network Meta-Analysis

Abstract

This study aimed to use Bayesian network meta-analysis to compare the efficacy and safety of biologics for systemic lupus erythematosus (SLE). A comprehensive and systematic search of electronic databases (PubMed, Medline, Cochrane Library, EMBASE, Web of Science, CNKI, and WanFang Data) was conducted from 2014 to September 2024. Our study only included randomized controlled trials with full articles that enrolled adult SLE patients treated with biologics, in comparison with standard therapy. The primary efficacy endpoints were SLE Responder Index 4 (SRI4) and BICLA (BILAG-Based Composite Lupus Assessment). The safety endpoints were adverse events (AEs) and serious adverse events (SAEs). R 4.4.3 and RStudio were used to conduct the network meta-analysis. RevMan 5.4 was used to assess the included literature. 29 randomized controlled trials with a total of 13,712 patients met the inclusion criteria. The network meta-analysis indicated that compared with standard therapy, telitacicept (OR 5.2, 95% CI 1.4-20.0) demonstrated superior efficacy in achieving SRI4 response, deucravacitinib (OR 1.6, 95% CI 1.0-2.5), and anifrolumab (OR 1.6, 95% CI 1.3-2.0) all exhibited significant BICLA response in moderate-to-severe SLE patients. Regarding safety, it was observed that there were no significant statistical differences among the various treatment options. Cluster analysis revealed that deucravacitinib exhibited the best efficacy-safety profile. Deucravacitinib suggested a favorable profile between efficacy and safety. Telitacicept showed the most pronounced improvement in SRI-4 response, but was associated with higher rates of AEs and SAEs, whereas anifrolumab and deucravacitinib displayed advantages in reducing SAEs. For patients with elevated baseline IFN signatures, anti-type I interferon biologics such as anifrolumab and sifalimumab are recommended to maximize clinical benefits. The reliance on indirect comparisons necessitates cautious interpretation of these findings, so further research should prioritize direct head-to-head trials to validate the efficacy and safety profiles of these biologics.

Keywords: Biologics; Network Meta-Analysis; SLE; Systemic Lupus Erythematosus.

Fig. 1

An overview of the literature search and screening process

Fig. 2

Risk of bias assessment. A Risk of bias across all studies. B Risk of bias for each item in each study

Fig. 3

Cumulative ranking probability plots for (A) SRI4 response, (B) SIDALE-2K, (C) LLDAS, (D) BICLA response, (E) SRI6 response, (F) BILAG, (G) adverse events and (H) serious adverse events

Fig. 4

Cluster analysis ranking chart of the efficacy and safety of the 17 interventions. The four colors represent the four clusters. x- and y-axles represent the efficacy and safety, respectively, the higher the value, the higher the efficacy or safety. The upper-right quadrant represents the favorable therapeutic zone (high-ranked efficacy/high-ranked safety), with node size proportional to composite benefit scores

Fig. 5

Comparing the proportion of SRI4 response of biologic therapy for SLE: a subgroup analysis at different level of IFN

Fig. 6

Funnel plot for (A) SRI4 response, (B) adverse events and (C) serious adverse events