Comparative effectiveness of immunosuppressive drugs and corticosteroids for lupus nephritis: a systematic review and network meta-analysis.
There is a lack of high-quality meta-analyses and network meta-analyses of immunosuppressive drugs for lupus nephritis. Our objective was to assess the comparative benefits and harms of immunosuppressive drugs and corticosteroids in lupus nephritis.



We conducted a systematic review and network meta-analysis (NMA) of trials of immunosuppressive drugs and corticosteroids in patients with lupus nephritis. We calculated odds ratios (OR) and 95 % credible intervals (CrI).



Sixty-five studies that met inclusion and exclusion criteria; data were analyzed for renal remission/response (37 trials; 2697 patients), renal relapse/flare (13 studies; 1108 patients), amenorrhea/ovarian failure (eight trials; 839 patients) and cytopenia (16 trials; 2257 patients). Cyclophosphamide [CYC] low dose (LD) and CYC high-dose (HD) were less likely than mycophenolate mofetil [MMF] and azathioprine [AZA], CYC LD, CYC HD and plasmapharesis less likely than cyclosporine [CSA] to achieve renal remission/response. Tacrolimus [TAC] was more likely than CYC LD to achieve renal remission/response. MMF and CYC were associated with a lower odds of renal relapse/flare compared to PRED and MMF was associated with a lower rate of renal relapse/flare than AZA. CYC was more likely than MMF and PRED to be associated with amenorrhea/ovarian failure. Compared to MMF, CYC, AZA, CYC LD, and CYC HD were associated with a higher risk of cytopenia.



In this systematic review and NMA, we found important differences between immunosuppressives used for the treatment of lupus nephritis. Patients and physicians can use this information for detailed informed consent in a patient-centered approach. Study limitations of between-study clinical heterogeneity and small sample size with type II error must be considered when interpreting these findings.







CRD42016032965.
Medicine Service, VA Medical Center, Birmingham, AL, USA. Jasvinder.md@gmail.com.|Department of Medicine at the School of Medicine, and Division of Epidemiology at the School of Public Health, University of Alabama at Birmingham, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL, 35294, USA. Jasvinder.md@gmail.com.|Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA. Jasvinder.md@gmail.com.
Jasvinder A
JA
Singh
Ottawa Heart Institute and the University of Ottawa, Ottawa, ON, Canada.
Alomgir
A
Hossain
Ottawa Heart Institute and the University of Ottawa, Ottawa, ON, Canada.
Ahmed
A
Kotb
Ottawa Heart Institute and the University of Ottawa, Ottawa, ON, Canada.
George A
GA
Wells
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000276:immunology; D016017:Odds Ratio; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D005938:Glucocorticoids; D007166:Immunosuppressive Agents
Cyclophosphamide; Glucocorticoids; Immunosuppressive drugs; Lupus; Lupus nephritis; Mycophenolate mofetil; Network meta-analysis; Renal relapse; Renal remission; Tacrolimus