Effectiveness and safety of B cell-targeting biologics in the treatment of lupus nephritis: a systematic review and network meta-analysis

ObjectivesTo evaluate the effectiveness and safety of different B cell-targeting biological agents combining with standard of care in patients with lupus nephritis (LN).MethodsComprehensive literature searches were conducted using PubMed, Embase, Web of Science, and Central in the Cochran Library, spanning from inception to May 20th, 2024. Randomized control trials (RCTs) comparing rituximab (RTX), belimumab, ocrelizumab, obinutuzumab, and anifrolumab in LN were selected. The primary outcomes of interest were related to complete renal remission (CRR), and partial renal remission (PRR). Additionally, we delved into safety outcomes, examining the occurrence of serious adverse events (SAEs), infections, and the discontinuation rates due to adverse events.ResultsA total of 6 RCTs with 1150 patients applying various B cell-targeting biological agents were included. Notably, ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that obinutuzumab (SUCRA 85.2%) has the highest potential superiority in improving CRR, followed by belimumab, ocrelizumab. Regarding the improvement in PRR, obinutuzumab (SUCRA 83.0%) has the highest potential superiority. In terms of safety, with a focus on SAEs, infections, and the discontinuation rates due to adverse events, the results were: SUCRA-based ranking indicated that RTX (SUCRA 74.1%) had the highest probability of postponing SAEs, followed by belimumab and obinutuzumab. Concerning infection reduction, anifrolumab (SUCRA 78.7%) had the highest potential superiority. Safety events monitoring infection occurred better with RTX than with standard therapy (OR = 3.57, 95% CI 1.02, 12.66) and were statistically different. For the discontinuation rates due to adverse events, RTX (SUCRA 88.6%) demonstrated the highest potential superiority.ConclusionsConcerning the effectiveness and safety outcomes, obinutuzumab, belimumab, and RTX plus standard of care may be superior to the current standard therapy as treatments for LN. This study protocol has been registered with PROSPERO, with a registration number of CRD42024548522.