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Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Treatments for Lupus Nephritis: A Systematic Review and Network Metaanalysis
Jasvinder A Singh1, Alomgir Hossain2, Ahmed Kotb2
1From the Medicine Service, Veterans Affairs (VA) Medical Center; Department of Medicine at the School of Medicine, and Division of Epidemiology at the School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama; Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota; University of California at San Francisco, San Francisco, California; University of Oregon, Portland, Oregon, USA; Ottawa Heart Institute and the University of Ottawa, Ottawa, Ontario, Canada.J.A. Singh, MBBS, MPH, Medicine Service, VA Medical Center, and Department of Medicine at the School of Medicine, and Division of Epidemiology at the School of Public Health, University of Alabama at Birmingham, and Department of Orthopedic Surgery, Mayo Clinic College of Medicine; A. Hossain, PhD, Ottawa Heart Institute and the University of Ottawa; A. Kotb, PhD, Ottawa Heart Institute and the University of Ottawa; A. Oliveira, PhD, Department of Medicine at the School of Medicine, and Division of Epidemiology at the School of Public Health, University of Alabama at Birmingham; A.S. Mudano, MPH, Department of Medicine at the School of Medicine, and Division of Epidemiology at the School of Public Health, University of Alabama at Birmingham; J. Grossman, MD, University of California at San Francisco; K. Winthrop, MD, MPH, University of Oregon; G.A. Wells, PhD, Ottawa Heart Institute and the University of Ottawa. Jasvinder.md@gmail.com.
Objective:
To compare benefits and harms of lupus nephritis (LN) induction and maintenance treatments.
Methods:
We performed a systematic review and Bayesian network metaanalyses of randomized controlled trials (RCT) of immunosuppressive drugs or corticosteroids (CS) in LN. OR and 95% credible intervals (CrI) were calculated.
Results:
There were 65 RCT that met inclusion and exclusion criteria. Significantly lower risk of endstage renal disease (ESRD; 17 studies) was seen with cyclophosphamide (CYC; OR 0.49, 95% CrI 0.25-0.92) or CYC + azathioprine (AZA; OR 0.18, 95% CrI 0.05-0.57) compared with standard-dose CS, and with high-dose (HD) CYC (OR 0.16, 95% CrI 0.03-0.61) or CYC + AZA (OR 0.10, 95% CrI 0.03-0.34) compared with HD CS. HD CS was associated with higher risk of ESRD compared with CYC (OR 3.59, 95% CrI 1.30-9.86), AZA (OR 2.93, 95% CrI 1.08-8.10), or mycophenolate mofetil (MMF; OR 7.05, 95% CrI 1.66-31.91). Compared with CS, a significantly higher proportion of patients had renal response (14 studies) when treated with CYC (OR 1.98, 95% CrI 1.13-3.52), MMF (OR 2.42, 95% CrI 1.27-4.74), or tacrolimus (TAC; OR 4.20, 95% CrI 1.29-13.68). No differences were noted for the risk of malignancy (15 studies). The risk of herpes zoster (17 studies) was as follows: OR (95% CrI) MMF versus CS 4.38 (1.02-23.87), CYC versus CS 6.64 (1.97-25.71), TAC versus CS 9.11 (1.13-70.99), and CYC + AZA versus CS 8.46 (1.99-43.61).
Conclusion:
Renal benefits and the risk of herpes zoster were higher for immunosuppressive drugs versus CS. Data on relative and absolute differences are now available, which can be incorporated into patient-physician discussions related to systemic lupus erythematosus medication use.
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