Belimumab combined with standard therapy does not increase adverse effects compared with a control treatment: A systematic review and meta-analysis of randomised controlled trials

The increasing administration of belimumab has demonstrated its biological benefits. Prior meta-analyses have examined the overall adverse events (AEs) associated with belimumab, but such knowledge needs to be updated with a high volume of new trials. However, little is known about the occurrence of AEs associated with different underlying diseases. This study aimed to address the safety of the intravenous (IV) administration of belimumab combined with standard of care (SoC) therapy in Systemic lupus erythematosus (SLE) patients.We used PubMed, Embase, and the Cochrane Library to systematically search for randomised controlled trials (RCTs) reporting AEs and specific AEs in SLE patients receiving belimumab and SoC therapy before 30 November 2021. We extracted the data of the eligible studies and calculated pooled risk ratios (RRs) and their 95% confidence intervals (CIs) in SLE patients receiving belimumab and SoC therapy and experiencing various AEs. The main outcomes were as follows: (1) any AEs, any serious AEs (SAEs), and any severe AEs; (2) serious organ specific adverse events; (3) adverse events of special interest (AESIs).Of the 1,621 studies identified, nine RCTs involving 7,974 patients were eligible for the meta-analysis. There were no significant differences between the experimental and control groups in terms of the incident of AEs: AEs (RR = 0.99, 95% CI: 0.97-1.02, P = 0.68), SAEs (RR = 0.91, 95% CI: 0.81-1.02, P = 0.09), and severe AEs (RR = 0.92, 95% CI: 0.75-1.14, P = 0.46). The pooled data also showed that there was no significant correlation between five types of SAEs grouped by organ class and the IV belimumab (10 mg/kg) intervention, except for 'infections and infestations' (RR = 0.82, 95% CI: 0.70-0.97, P = 0.02) and 'musculoskeletal and connective tissue disorders' (RR = 0.46, 95% CI: 0.32-0.67, P < 0.0001). In addition, we found no significant association between AESIs and the IV administration of belimumab (10 mg/kg) (all malignancies: RR = 1.53, 95% CI: 0.69-3.36, P = 0.3; all post-infusion systemic reactions: RR = 1.05, 95% CI: 0.85-1.30, P = 0.63; depression: RR = 1.42, 95% CI: 0.92-2.20, P = 0.11; serious depression: RR = 2.60, 95% CI: 0.85-7.93, P = 0.09; suicide or self-injury: RR = 0.97, 95% CI: 0.48-1.96, P = 0.92; serious suicide or self-injury: RR = 1.26, 95% CI: 0.59-2.70, P = 0.56).According to the results of the meta-analysis, SLE patients did not have significantly increased risk of experiencing any type of AEs when receiving SoC therapy. Special caution should be exercised during close follow-ups and individual clinical management before drug prescription.