Next Stop in the Treatment of Refractory Systemic Lupus Erythematosus: B-cell Targeted Combined Therapy

Systemic lupus erythematosus (SLE) is an autoimmune condition with a wide spectrum of clinical manifestations encompassing most organs and systems. Its treatment approach includes different immunomodulatory treatments, of which B-cell targeted therapies are part of. Rituximab (an anti-CD20 antibody) had encouraging results in observational studies but failed when tested in clinical trials. It is theorized that this could have been partially due to BAFF upregulation, leading to rituximab failure. Therefore, targeting BAFF with belimumab after rituximab therapy, may have a synergic effect in SLE. We review the available observational data regarding sequential rituximab/belimumab therapy in SLE patients. Twenty-four patients from 6 studies were included. The results suggest a benefit with this combined therapy, with reduction of the mean SLEDAI. However, there was significant drug regimen and patient selection heterogeneity. Further randomized clinical trials are needed to examine this drug sequencing protocol in SLE patients.