Guide
Systemic lupus erythematosus (SLE) is a chronic, diffuse connective tissue disease with an unknown cause that affects multiple systems throughout the body. Among them, lupus nephritis (LN) is the main manifestation of kidney injury in SLE patients, up to 90% of SLE patients can find kidney lesions through renal biopsy, about 50% of patients have clinical kidney injury symptoms, and about 5%-30% of patients will develop end-stage renal disease. Therefore, it is important for LN patients to explore more effective and safe treatment options.
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September 23, 2024
Current standard induction regimens for LN mainly include mycophenolate mofetil (MMF) or cyclophosphamide (CYC) plus glucocorticoids (GCs). However, these regimens have limited rates of complete renal response (CRR) and a high incidence of adverse effects. With the in-depth study of the pathogenesis of LN, more and more biologics have emerged, providing new options for the treatment of LN. However, due to the lack of head-to-head comparative studies, clinicians face challenges in assessing the relative effectiveness and safety of these treatment options, resulting in biologics often being used as alternative therapies after conventional treatment has failed.
Recently, the team from the Department of Nephrology of Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology published a study in Renal Failure, comparing the efficacy and safety of biologics, multi-target therapy (tacrolimus + MMF + GCs) and standard therapy in LN induction therapy through systematic review and online meta-analysis, aiming to provide a reference for clinicians.
Research Methods:
Randomised controlled trials (RCTs) of adults with LN who received biologics or multi-targeted therapy versus standard care were included. The primary efficacy measures included CRR and overall renal response rate (TRR), and the safety measures included serious adverse events (SAEs), serious infections, and all-cause mortality.
Findings:
This meta-analysis screened 4718 studies, and after removing duplicate studies and reviewing titles, keywords, and abstracts, 52 studies were selected for full-text evaluation, and 10 RCTs including 1989 patients were included with follow-up of 24 to 104 weeks.
肾脏完全缓解率（CRR）与标准疗法相比，多靶点治疗[比值比（OR） 2.78（95%CI:1.81–4.26）]、伏环孢素23.7 mg[OR 2.61（95%CI:1.79–3.79）]、奥妥昔单抗[OR 2.41（95%CI:1.11–5.25）]、伏环孢素39.5 mg[OR 1.90（95%CI:1.07–3.37）]和贝利尤单抗[OR 1.75（95%CI:1.13–2.70）]用于LN治疗的CRR均显著更高（图1、图2）。
Figure 1: Comparative CRR results for all drugsMulti: multi-target therapy; BEL: belimumab; OBI: obinutuzumab; RTX: rituximab; RTX+BEL: rituximab + belimumab; BAR: baricitinib; VOC23.7 mg: volucisine 23.7 mg; VOC39.5 mg: vorcisporine 39.5 mg; ANI300: anirulumab 300 mg; ANI900: anirulumab 900 mg; SOC: Standard Therapy
Figure 2: Forest plot comparing the relative efficacy of different drug treatments in achieving CRR
肾脏总缓解率（TRR）与标准疗法相比，多靶点治疗[OR 3.20（95%CI:1.98–5.19）]、巴瑞替尼[OR 3.29（95%CI:1.08–9.95）]、奥妥珠单抗[OR 2.87（95%CI:1.37–6.00）]、伏环孢素[OR 2.16（95%CI:1.40–3.34）]和贝利尤单抗[OR 1.56（95%CI:1.07–2.27）]用于LN治疗的TRR均显著更高（图3）。
Figure 3: Comparison of TRRs for all drugs
Safety analysis of data on SAEs was reported in eight studies with a total of 1904 patients, and the analysis showed no significant difference in the incidence of SAEs among the 10 interventions, with a relatively low incidence of SAEs with rituximab (Figure 4).
Figure 4: Comparison of the incidence of serious adverse events across all drugs
Data on severe infection were reported in six studies with a total of 1469 patients, and the analysis showed no significant difference in the incidence of severe infection between the eight interventions, with a relatively low incidence of severe infection with anilulumab (Figure 5).
Figure 5: Comparison of the incidence of serious infections across all drugs
Data on all-cause mortality were reported in eight studies with a total of 1666 patients, and the analysis showed no significant difference in all-cause mortality between the nine interventions, with a relatively low all-cause mortality with fusporine (Figure 6).
Figure 6: Comparison of all-cause mortality for all drugs
Research Discussion
As an important complication of SLE, the optimization of LN treatment regimen is of great significance to improve the prognosis of patients. This study provides an important reference for the treatment of LN through network meta-analysis, but considering that the study population is limited to Asian patients, its generalizability needs to be further verified. At the same time, it should be noted that although the network meta-analysis combines direct and indirect evidence, the reliability of its results is still affected by factors such as sample size and study quality.
In the future, with the development of more high-quality RCTs, especially studies involving multi-regional and multi-ethnic patients, the efficacy and safety of LN treatment regimens will be further validated. At the same time, it will also be an important direction for future research to formulate more precise treatment plans for different LN pathological types, disease activity and individual differences of patients.
Conclusions of the study
In summary, multi-target therapy has the best efficacy in achieving complete renal remission, but the incidence of serious adverse events is high, and the safety profile of rituximab is relatively good, and the efficacy and safety of belimumab and obinutuzumab are good. As the study subjects are mainly in the Asian population, the conclusions should be interpreted with caution, and future studies should provide more direct evidence to evaluate and compare the efficacy and safety of different biologics, multi-target therapies and conventional treatments in the treatment of LN.
引用文献：Tian GQ, Li ZQ. Efficacy and safety of biologics, multitarget therapy, and standard therapy for lupus nephritis: a systematic review and network meta-analysis. Ren Fail. 2024; 46(2):2395451. doi:10.1080/0886022X.2024.2395451