To Örebro University

OBJECTIVES: To determine the effect of antimalarial agents (AMA) and different doses and pharmaceutical forms of belimumab on preventing renal flares in patients with systemic lupus erythematosus (SLE) treated for extra-renal disease.

METHODS: We pooled data from the BLISS-52, BLISS-76, BLISS-SC and BLISS-Northeast Asia trials of belimumab (N = 3225), that included patients with active SLE yet no severe ongoing nephritis. Participants were allocated to receive intravenous belimumab 1 mg/kg, intravenous belimumab 10 mg/kg, subcutaneous belimumab 200 mg, or placebo in addition to standard therapy. We estimated hazards of renal flare development throughout the study follow-up (52-76 weeks) using Cox regression analysis.

RESULTS: In total, 192 patients developed a renal flare after a median of 197 days. Compared with placebo, the risk of renal flares was lower among patients receiving intravenous belimumab 10 mg/kg (HR: 0.62; 95% CI: 0.41-0.92; p = 0.018) and intravenous belimumab 1 mg/kg (HR: 0.42; 95% CI: 0.22-0.79; p = 0.007), while no significant association was found for subcutaneous belimumab 200 mg. AMA use yielded a lower hazard of renal flares (HR: 0.66; 95% CI: 0.55-0.78; p < 0.001). The protection conferred was enhanced when belimumab and AMA were co-administered; the lowest flare rate was observed for the combination intravenous belimumab 1 mg/kg and AMA (18.5 cases per 1000 person-years).

CONCLUSIONS: The protection conferred from belimumab against renal flare development in patients treated for extra-renal SLE appears enhanced when belimumab is administered along with AMA. The prominent effect of low-dose belimumab warrants investigation of the efficacy of intermediate doses.