The Evolving Landscape of Targeted Therapies in Systemic Lupus Erythematosus: A Review of Phase 3 Clinical Trials

Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease characterized by multisystem involvement and substantial morbidity. Although survival has improved over recent decades, disease burden remains considerable due to cumulative organ damage, comorbidities, and treatment-related toxicity, particularly from long-term glucocorticoid use. Advances in the understanding of SLE immunopathogenesis have led to the development of targeted therapies. Currently approved agents include belimumab and anifrolumab, while obinutuzumab has been approved for lupus nephritis and has also demonstrated significant efficacy in phase III trials in SLE. Several additional agents are in late-stage clinical development, including litifilimab (targeting plasmacytoid dendritic cells), telitacicept and ianalumab (BAFF/APRIL and B-cell modulation), dapirolizumab pegol (CD40L blockade), deucravacitinib and upadacitinib (TYK2/JAK inhibition), and cenerimod (S1P11 modulation). This narrative review summarizes current phase III evidence and emerging therapeutic strategies, highlighting the ongoing transition toward precision medicine and individualized treatment approaches in SLE.