Network meta-analysis of triple immunosuppressive therapies and standard of care for induction of remission of active lupus nephritis.

BackgroundIn patients with active lupus nephritis (LN), 8 different triple immunosuppressive therapies have been compared to the standard of care (SOC) of double immunosuppressive therapy in 12 induction randomized clinical trials (RCTs). The triple immunosuppressive therapies of SOC+Tacrolimus, SOC+Voclosporin, SOC+Belimumab, and SOC+Obinutuzumab compared to SOC alone demonstrated significantly higher remission of LN without excessive risk of serious adverse events (SAEs) and serious infectious events (SIEs) in RCTs. Direct or indirect comparisons among triple immunosuppressive therapies have not been studied. In this network meta-analysis (NMA), we systematically provide indirect comparisons of the relative efficacy and safety of triple immunosuppressive therapies, ranking them according to efficacy achieving primary renal remission (PRR) of LN and safety reducing the risk of SAEs and SIEs.ResultsThe NMA included predominantly women with LN. In direct pairwise comparisons, SOC+Tacrolimus (benefit ratio 1.91 [95% Credible Interval 1.45 to 2.56]), SOC+Voclosporin (1.69 [1.30 to 2.23]), SOC+Obinutuzumab (1.41 [1.09 to 1.84]), and SOC+Belimumab (1.32 [1.04 to 1.69]) had significantly higher PRR compared to SOC alone. In indirect pairwise comparisons, patients who received SOC+Tacrolimus compared to SOC+Rituximab (2.30 [1.27 to 4.20]), SOC+Anifrolumab (1.98 [1.07 to 3.52]), SOC+Ocrelizumab (1.81 [1.12 to 2.82]), and SOC+Abatacept (1.78 [1.07 to 2.91]) had significantly higher PRR. Patients who received SOC+Voclosporin compared to SOC+Rituximab (2.03 [1.14 to 2.68]) had significantly higher PRR. SOC+Belimumab, SOC+Obinutuzumab, SOC+Voclosporin and SOC+Tacrolimus ranked as effective therapies inducing PRR with SUCRA probability scores between 61.14% and 95.12%. Risk ratios of SAE and SIE were not significantly different among the immunosuppressive therapies.ConclusionIn patients with LN, induction therapies of SOC with calcineurin inhibitors had the highest relative benefit achieving remission of LN.