A randomised biomarker enrichment trial: IgA2 anti-DNA antibodies as a biomarker of response to belimumab after rituximab in systemic lupus erythematosus - STRATIFY lupus

A simple blood test could determine which lupus patients will benefit from a specific two-drug sequence, sparing others from ineffective treatment and unnecessary side effects. The problem: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease where the immune system attacks the body's own tissues. Many patients do not respond to standard therapies, and doctors lack reliable ways to predict who will benefit from powerful but risky treatments like rituximab (a B-cell depleting antibody) followed by belimumab (which blocks a survival signal for B cells). The STRATIFY lupus trial tests whether patients with high levels of a specific antibody—IgA2 anti-dsDNA—in their blood are far more likely to achieve a major clinical response when given belimumab after rituximab, compared to rituximab alone. The trial also aims to keep corticosteroid and immunosuppressant doses low, reducing long-term toxicity. If successful, this biomarker enrichment strategy could transform how clinicians select treatments for refractory SLE. Instead of a trial-and-error approach, a simple blood test would identify the subset of patients most likely to respond to combination B-cell therapy, improving outcomes while minimising drug exposure for those unlikely to benefit. The trial samples will also deepen understanding of lupus pathogenesis and how B-cell targeted therapies work, potentially guiding future drug development.