Background We aimed 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 active extra-renal disease.

Methods We pooled data from the BLISS-52, BLISS-76, BLISS-SC and BLISS-Northeast Asia (NEA) randomised clinical trials of belimumab (N=3225), that included seropositive, active SLE patients with no active severe lupus nephritis (LN). Participants were allocated to receive intravenous (IV) belimumab 1 mg/kg (N=559), IV belimumab 10 mg/kg (N=1033), subcutaneous (SC) belimumab 200 mg (N=556) or placebo (N=1077) in addition to standard therapy. The outcome of the present post-hoc analysis was development of renal flares, defined according to the analysis plan within the BLISS programme. The hazard of renal flare was assessed with Cox proportional hazards regression models, adjusted for age, sex, ethnicity, previous renal involvement, baseline proteinuria and glomerular filtration rate, and use of glucocorticoids and immunosuppressants.

Results Demographic and clinical characteristics are shown in table 1. 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 IV belimumab 10 mg/kg (HR: 0.63; 95% CI: 0.45–0.87; p=0.005) and IV belimumab 1 mg/kg (HR: 0.40; 95% CI: 0.23–0.73; p=0.002) but not those receiving SC belimumab 200 mg. AMA use yielded a lower hazard of renal flares (HR: 0.65; 95% CI: 0.49–0.88; p=0.005). The protection conferred was enhanced when belimumab and AMA were co-administered, and the lowest flare rate was observed for the combination IV belimumab 1 mg/kg and AMA (18.5 cases per 1000 person-years).

Conclusions Belimumab in combination with AMA prevent against renal flares in patients treated for extra-renal SLE. The prominent effect of low-dose belimumab warrants investigation of the efficacy of intermediate doses.