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

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Abstract

Objectives

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).

Method

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.

Results

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.

Conclusions

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

Key Points

• Compared with corticosteroids + single-agent immunosuppressive therapy, corticosteroids + doublet immunosuppressive therapy without biologics had a significantly higher overall response rate in active proliferative lupus nephritis.

• Compared with corticosteroids + single-agent immunosuppressive therapy, corticosteroids + doublet immunosuppressive therapy including biologics improved overall response rate only for refractory severe lupus nephritis.

• A larger change from baseline in SLE-DAI scores and a higher negative conversion ratio of anti-dsDNA were observed with corticosteroids + doublet immunosuppressive therapy than with corticosteroids + single-agent immunosuppressive therapy.

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Funding

This study was supported by a grant from the National Natural Science Foundation of China (81670641); a grant from the Guangdong Science and Technology Department (2014A020212062); and a grant from the Guangzhou Science Technology and Innovation Commission (201707010111).

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Author notes

  1. The authors Bo Liu, Qiyun Ou, and Ying Tang contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. Department of Nephrology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China

    Bo Liu, Ying Tang, Sha Fu, Peifen Liang, Zhenjian Xu & Anping Xu

  2. Department of Ultrasound in Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China

    Qiyun Ou

  3. Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China

    Yunfang Yu

  4. The First Clinical Medical College, Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China

    Yongjian Chen

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  1. Bo Liu
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Contributions

BL, YT, and APX designed the study. SF and PFL performed the literature searching and screening. BL, QYO, and YT extracted the data. YFY, ZJX, and YJC performed the statistical analysis. BL, QYO, and YT wrote the manuscript. All authors approved the final version of the manuscript.

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Correspondence to Anping Xu.

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Liu, B., Ou, Q., Tang, Y. et al. Corticosteroids combined with doublet or single-agent immunosuppressive therapy for active proliferative lupus nephritis. Clin Rheumatol 38, 2519–2528 (2019). https://doi.org/10.1007/s10067-019-04596-0

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