Belimumab efficacy in mucocutaneous manifestations of systemic lupus erythematosus: a large post hoc analysis of five phase III clinical trials

Objective: To determine the efficacy of belimumab on mucocutaneous manifestations of SLE in a large integrative analysis. Methods: Using data from five phase III clinical trials (BLISS-52; BLISS-76; BLISS-NEA; EMBRACE; BLISS-SC; N = 3086), we investigated the effect of belimumab vs. placebo on top of standard therapy on inducing improvement in mucocutaneous BILAG (mcBILAG) and mucocutaneous SLE Disease Activity Index 2000 (mcSLEDAI-2K), and on preventing mcBILAG flares. We employed logistic and Cox regression analysis, adjusting for trial variance. Results: Belimumab was superior to placebo in inducing mcBILAG (week-52 OR: 1.29; 95% CI: 1.07-1.57; P = 0.008) and mcSLEDAI-2K (week-52 OR: 1.37; 95% CI: 1.16-1.62; P< 0.001) improvement, as well as in inducing sustained (>= 2 visits, maintained through week 52) mcBILAG (HR: 1.23; 95% CI: 1.07-1.41; P = 0.003) and mcSLEDAI-2K (HR: 1.24; 95% CI: 1.17-1.31; P < 0.001) improvement. These associations held true for patients with SLEDAI-2K >= 10 and positive anti-dsDNA levels at baseline, but not their counter groups. Belimumab prevented mcBILAG flares to a greater extent than placebo in patients with positive anti-dsDNA levels (HR: 0.70; 95% CI: 0.50-0.98; P = 0.035) and with a near-significant separation in patients with baseline SLEDAI-2K >= 10 (HR: 0.71; 95% CI: 0.51-1.00; P = 0.050), whereas no difference was seen in their counter groups. Conclusion: Belimumab is superior to placebo in inducing improvement and in preventing flares in the mucocutaneous domain of SLE, especially in patients with high disease activity and in serologically active patients.