Comparative effectiveness and safety of biologics and targeted small-molecule therapies plus stable background therapy in systemic lupus erythematosus: a systematic review and network meta-analysis

Objective To compare the efficacy and safety of biologics and targeted small molecule drugs plus stable background therapy for the systemic lupus erythematosus (SLE). Methods A systematic search was conducted across PubMed, EMBASE and Cochrane Library for eligible randomized controlled trials (RCTs), and a network meta-analysis (NMA) was performed to investigate the efficacy and safety of biological agents and targeted small molecule drugs added to stable background therapy in SLE. The evaluation indicators included the rates of SLE Responder Index (SRI-4) response, BILAG-based Composite Lupus Assessment (BICLA) response, Cutaneous Lupus Erythematosus Disease Area and Severity Index-50 (CLASI-50), Lupus Low Disease Activity State (LLDAS), adverse events (AEs), serious adverse events (SAEs) and infection-related adverse events. Results A total of 32 studies were included, involving 17,121 patients. For SRI-4 response, Telitacicept was superior to Belimumab and Ustekinumab outperformed Epratuzumab. Upadacitinib demonstrated superior efficacy versus Baricitinib for both BICLA response and LLDAS attainment. Deucravacitinib and Anifrolumab were more effective for CLASI-50 achievement than Baricitinib. Anifrolumab, Iberdomide, and Telitacicept were associated with a higher incidence of AEs (e.g., upper respiratory tract infections, urinary tract infection, and herpes zoster) compared with other interventions, which may be related to their immunomodulatory mechanisms of action. Cenerimod was associated with the lowest risk of SAEs, and IL-2 showed the lowest risk of infection-related AEs. Conclusions Telitacicept and Ustekinumab demonstrated superior efficacy for SRI-4 response; Upadacitinib superior for BICLA response and LLDAS achievement; Deucravacitinib and Anifrolumab showed advantages in CLASI-50 improvement, suggesting therapeutic potential for SLE with cutaneous manifestations. Although current findings indicate that these interventions have favorable efficacy and safety profiles, their long-term efficacy and safety still require further investigation and validation in the future. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42024594766.