Corticosteroids combined with doublet or single-agent immunosuppressive therapy for active proliferative lupus nephritis

We performed a meta-analysis to assess whether corticosteroids (C) plus (+) doublet immunosuppressive therapy (IT) is superior to the classical combination of C with single-agent IT in active proliferative lupus nephritis (LN).

Randomized trials evaluating the benefits and risks of C+doublet versus single-agent IT in active proliferative LN were obtained by searching PubMed, EMBASE, and Cochrane Central Register. The primary outcome was overall response rate (ORR). The secondary outcomes were the change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLE-DAI) score, negative conversion ratio of anti-double-stranded DNA (anti-dsDNA), and adverse events. The PROSPERO registry number is CRD42017068491.

Eleven trials with 1855 patients were included. Compared with C+single-agent IT, C+doublet IT had a significantly higher ORR (relative risk [RR], 1.22; 95% confidence interval [CI], 1.09 to 1.35; P < 0.01). In a subgroup analysis, C+doublet IT without biologics had a significantly higher ORR than C+single-agent IT (RR, 1.30; 95% CI, 1.13 to 1.50; P < 0.01), while C+doublet IT including biologics improved ORR only for refractory severe LN (RR, 1.46; 95% CI, 1.09 to 1.96; P = 0.012). A larger change from baseline in SLE-DAI scores (standardized mean difference, − 0.49; 95% CI, − 0.68 to − 0.30; P < 0.01) and a higher negative conversion ratio of anti-dsDNA (RR, 1.34; 95% CI, 1.06 to 1.69; P = 0.014) were observed with C+doublet IT than with C+single-agent IT. The rates of adverse events were similar between the two regimens.

Compared with single-agent IT, the combination of C and doublet IT without biologics improved clinical outcomes in active proliferative LN.