•   Results from a phase II RCT (NCT02908100) showed that fenebrutinib treatment in patients with moderate or severeactive SLE was associated with a significant reduction in CD19+ B cells, anti-dsDNA levels, and BTK-dependentsignature in plasmablasts, but the primary clinical efficacy endpoint (SRI-4) was not met. Here, CD19 is linked to systemic lupus erythematosus.