systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with diverse clinical manifestations including nephritis, arthritis, serositis, cytopenias, and central nervous system involvement. Despite decades of off-label use of hydroxychloroquine and immunosuppressants, only three drugs have been specifically approved for SLE in the past 60 years β€” belimumab, anifrolumab, and voclosporin (for lupus nephritis) β€” reflecting the extraordinary challenge of conducting trials in a heterogeneous, relapsing-remitting condition.
Active trials investigate obinutuzumab (anti-CD20) for lupus nephritis, dapirolizumab pegol (anti-CD40L), deucravacitinib (TYK2 inhibitor), iberdomide (CELMoD agent), telitacicept (TACI-Fc fusion targeting BLyS and APRIL), and CAR-T cell therapy for severe refractory SLE. Patient selection using type I interferon gene expression signatures, anti-dsDNA titers, and complement levels guides both eligibility and endpoint assessment.
SLE trials use SLEDAI or BILAG disease activity scores at baseline; lupus nephritis trials typically require kidney biopsy confirmation of Class III/IV or V nephritis.