In this post hoc analysis of five foundational and explorative phase III RCTs assessing the clinical efficacy of belimumab in patients with SLE, belimumab conferred significantly greater benefit than placebo based on BICLA criteria for treatment response in a pooled analysis and particularly among patients with high disease activity (SLEDAI-2K≥10), anti-dsDNA positivity and/or low complement C3 and/or C4 levels at baseline. The gene discussed is C4A; the disease is systemic lupus erythematosus.