Multitarget therapy versus intravenous cyclophosphamide in the induction treatment of lupus nephritis: a metaanalysis of randomized controlled trials

Authors: JIN DENG, LEI LUO, LIN ZHU, HUAN XIE, HONG-PING XIE

Abstract: Background/aim: Multitarget therapy for lupus nephritis (LN) remains in its exploratory phrase and the recent evidence is insufficient. This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF), tacrolimus (TAC), and steroids (multitarget therapy) versus intravenous cyclophosphamide (IVC) and steroids in induction treatment of LN. Materials and methods: We searched for randomized controlled trials of MMF plus TAC versus IVC in LN using PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the China Biology Medicine Database, and the China National Knowledge Infrastructure Database. We assessed the retrieved citations and selected studies according to predefined inclusion and exclusion criteria. Results: In total, we identified 8 trials including 801 patients. The metaanalysis revealed that overall multitarget therapy is more effective at inducing complete renal remission compared with IVC (RR: 1.94, 95% CI: 1.61-2.33; P < 0.00001). In terms of LN classification, multitarget therapy exhibited superiority compared with IVC for inducing complete remission of class IV LN (RR: 1.52, 95% CI: 1.10- 2.08; P = 0.01), class V LN (RR: 4.24, 95% CI: 1.30-13.88; P = 0.02), and class V+IV LN (RR: 2.29, 95% CI: 1.45-3.62; P = 0.0004); however, no superiority was noted for class III LN or class V+III LN. The rates of gastrointestinal symptoms, abnormal liver function, leukopenia, and irregular menstruation were significantly reduced in the multitarget therapy group compared with the IVC group for LN. Nevertheless, the multitarget therapy group more frequently exhibited new-onset hypertension compared with the IVC group. Conclusion: Multitarget therapy is more effective than IVC in the induction treatment of LN in Chinese patients and exhibits a better safety profile.

Keywords: Lupus nephritis, cyclophosphamide, mycophenolate mofetil, tacrolimus, metaanalysis

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