Efficacy and safety of novel biologics in the treatment of lupus nephritis based on registered clinical trials: a systematic review and network meta-analysis

Abstract

To compare the clinical effectiveness and safety of novel biologics for the treatment of lupus nephritis based on a reticulated meta-analysis approach. Registered clinical trials in 4 major databases (PubMed, Embase, Web of Science, The Cochrane Register of Clinical Trials) and ClinicalTrials.gov were systematically searched with a search time frame of build to June 2022. And we screened registered randomized controlled clinical trials of biologics for the treatment of lupus nephritis according to the protocol's nadir criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 and Review Manager 5.3 software to compare and rank differences in effectiveness and safety between the biologics. A total of 10 registered randomized controlled clinical trials involving 2148 subjects were included in this study. The interventions were ranked from best to worst in terms of the primary outcome indicator of effectiveness, renal complete remission: belimumab > anifrolumab (900 + 300) mg > obinutuzumab > ocrelizumab 400 mg > abatacept 30/10 mg/kg > belimumab + rituximab > abatacept 10/10 mg/kg > abatacept (30/10 + 10/10) mg/kg > placeo > ocrelizumab 1000 mg > rituximab > anifrolumab 300 mg, belimumab was superior to placebo [OR = 1.75, 95% CI (1.13, 2.70)] and anifrolumab 300 mg [OR = 3.27, 95% CI (1.05, 10.14)], anifrolumab (900 + 300) mg was superior to anifrolumab 300 mg [OR = 3.56, 95% CI (1.30, 9.76)], and all were statistically significant. The ranking of each intervention in terms of overall renal remission for secondary outcome indicators from best to worst was: obinutuzumab > belimumab + rituximab > anifrolumab (900 + 300) mg > ocrelizumab 1000 mg > ocrelizumab 400 mg > belimumab > rituximab 1000 mg > abatacept 30/10 mg/kg > abatacept (30/10 + 10/10) mg/kg > placeo > abatacept 10/10 mg/kg > anifrolumab 300 mg, obinutuzumab was superior to placebo [OR = 2.27, 95% CI (1.11, 4.67)] and belimumab was also superior to placebo [OR = 1.56, 95% CI (1.07, 2.27)], and all were statistically significant. In terms of safety, with a focus on serious adverse events and serious infections, the results were: Serious adverse events at 1 year of monitoring occurred better with ocrelizumab 1000 mg than ocrelizumab 400 mg [OR = 0.51, 95% CI (0.29, 0.89)] and were statistically different; serious adverse events at 2 years of monitoring infection adverse events occurred better with obinutuzumab than with abatacept (30/10 + 10/10) mg/kg [OR = 0.24, 95% CI (0.07, 0.81)] and were statistically different. The safety of the new biologics in combination with conventional standard therapies is generally good, but it is belimumab and obinutuzumab that are most effective in achieving complete and overall remission in the kidney. This study protocol has been registered with PROSPERO, with a registration number of CRD42021262498.

Keywords: Biologics; Effectiveness; Lupus nephritis; Network meta-analysis; Safety.