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Erschienen in: Zeitschrift für Rheumatologie 7/2023

20.09.2021 | Originalien

A network meta-analysis of randomized controlled trials comparing the effectiveness and safety of voclosporin or tacrolimus plus mycophenolate mofetil as induction treatment for lupus nephritis

verfasst von: Young Ho Lee, MD, PhD, Gwan Gyu Song

Erschienen in: Zeitschrift für Rheumatologie | Ausgabe 7/2023

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Abstract

Aim

This study aimed to compare the effectiveness and safety of voclosporin + mycophenolate mofetil (MMF), tacrolimus + MMF, and monotherapy with MMF or cyclophosphamide as induction treatment for lupus nephritis.

Methods

The study included randomized controlled trials (RCTs) that evaluated the effectiveness and safety of voclosporin + MMF, tacrolimus + MMF, and monotherapy for induction treatment in patients with lupus nephritis. To incorporate direct and indirect evidence from RCTs, we used a Bayesian network meta-analysis.

Results

Four RCTs, including 936 participants, met the inclusion criteria. Tacrolimus + MMF substantially increased the incidence of complete remission relative to that following monotherapy (odds ratio [OR] 2.85; 95% credible interval [CrI] 1.87–4.39). Tacrolimus + MMF was also more effective than voclosporin + MMF (OR 1.43; 95% CrI 0.80–2.57). Tacrolimus + MMF showed the greatest chance of being the optimal treatment for overall response (surface under the cumulative ranking curve [SUCRA] = 0.942), followed by voclosporin + MMF (SUCRA = 0.558) and monotherapy (SUCRA = 0.001). In terms of safety based on severe event rates, monotherapy had the greatest chance of being the safest treatment (SUCRA = 0.903), followed by voclosporin + MMF (SUCRA = 0.517) and tacrolimus + MMF (SUCRA = 0.081).

Conclusion

Tacrolimus + MMF and voclosporin + MMF were more effective than monotherapy, and tacrolimus + MMF was the most effective induction treatment for lupus nephritis patients. However, tacrolimus + MMF did pose a greater risk of serious adverse events than monotherapy.
Literatur
1.
Zurück zum Zitat Neumann K, Wallace DJ, Azen C, Nessim S, Fichman M, Metzger AL, Klinenberg JR (1995) Lupus in the 1980s: III. Influence of clinical variables, biopsy, and treatment on the outcome in 150 patients with lupus nephritis seen at a single center. Semin Arthritis Rheum 25:47–55CrossRefPubMed Neumann K, Wallace DJ, Azen C, Nessim S, Fichman M, Metzger AL, Klinenberg JR (1995) Lupus in the 1980s: III. Influence of clinical variables, biopsy, and treatment on the outcome in 150 patients with lupus nephritis seen at a single center. Semin Arthritis Rheum 25:47–55CrossRefPubMed
2.
Zurück zum Zitat Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, Li L‑S, Mysler E, Sanchez-Guerrero J, Solomons N (2009) Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 20:1103–1112CrossRefPubMedPubMedCentral Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, Li L‑S, Mysler E, Sanchez-Guerrero J, Solomons N (2009) Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 20:1103–1112CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Li X, Ren H, Zhang Q, Zhang W, Wu X, Xu Y, Shen P, Chen N (2012) Mycophenolate mofetil or tacrolimus compared with intravenous cyclophosphamide in the induction treatment for active lupus nephritis. Nephrol Dial Transplant 27:1467–1472CrossRefPubMed Li X, Ren H, Zhang Q, Zhang W, Wu X, Xu Y, Shen P, Chen N (2012) Mycophenolate mofetil or tacrolimus compared with intravenous cyclophosphamide in the induction treatment for active lupus nephritis. Nephrol Dial Transplant 27:1467–1472CrossRefPubMed
4.
Zurück zum Zitat Sung-Eun C, Dong-Jin P, Ji-Hyoun K, Kyung-Eun L, Haimuzi X, Ji Shin L, Choi Y‑D, Shin-Seok L (2019) Comparison of renal responses to cyclophosphamide and mycophenolate mofetil used as induction therapies in Korean patients with lupus nephritis. J Rheum Dis 26:57–65CrossRef Sung-Eun C, Dong-Jin P, Ji-Hyoun K, Kyung-Eun L, Haimuzi X, Ji Shin L, Choi Y‑D, Shin-Seok L (2019) Comparison of renal responses to cyclophosphamide and mycophenolate mofetil used as induction therapies in Korean patients with lupus nephritis. J Rheum Dis 26:57–65CrossRef
5.
Zurück zum Zitat Touma Z, Gladman DD, Urowitz MB, Beyene J, Uleryk EM, Shah PS (2011) Mycophenolate mofetil for induction treatment of lupus nephritis: a systematic review and metaanalysis. J Rheumatol 38:69–78CrossRefPubMed Touma Z, Gladman DD, Urowitz MB, Beyene J, Uleryk EM, Shah PS (2011) Mycophenolate mofetil for induction treatment of lupus nephritis: a systematic review and metaanalysis. J Rheumatol 38:69–78CrossRefPubMed
6.
Zurück zum Zitat Ayoub I, Rovin BH (2017) Calcineurin inhibitors in the treatment of lupus nephritis: a hare versus turtle story? J Am Soc Nephrol 28(12):3435–3437CrossRefPubMedPubMedCentral Ayoub I, Rovin BH (2017) Calcineurin inhibitors in the treatment of lupus nephritis: a hare versus turtle story? J Am Soc Nephrol 28(12):3435–3437CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Yo J, Barbour T, Nicholls K (2019) Management of refractory lupus nephritis: challenges and solutions. Open access rheumatology. Res Rev 11:179 Yo J, Barbour T, Nicholls K (2019) Management of refractory lupus nephritis: challenges and solutions. Open access rheumatology. Res Rev 11:179
9.
Zurück zum Zitat Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema I, Berden JH, Boletis J, Cervera R, Dörner T et al (2012) Joint European league against rheumatism and European renal association—European dialysis and transplant association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis 71(11):1771–1782CrossRefPubMed Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema I, Berden JH, Boletis J, Cervera R, Dörner T et al (2012) Joint European league against rheumatism and European renal association—European dialysis and transplant association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis 71(11):1771–1782CrossRefPubMed
11.
Zurück zum Zitat Kino T, Hatanaka H, Miyata S et al (1987) FK-506, a novel immunosuppressant isolated from a streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J Antibiot (Tokyo) 40:1256–1265CrossRefPubMed Kino T, Hatanaka H, Miyata S et al (1987) FK-506, a novel immunosuppressant isolated from a streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J Antibiot (Tokyo) 40:1256–1265CrossRefPubMed
12.
Zurück zum Zitat Rovin BH, Teng YO, Ginzler EM, Arriens C, Caster DJ, Romero-Diaz J, Gibson K, Kaplan J, Lisk L et al (2021) Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 397(10289):2070–2080. https://doi.org/10.1016/S0140-6736(21)00578-XCrossRefPubMed Rovin BH, Teng YO, Ginzler EM, Arriens C, Caster DJ, Romero-Diaz J, Gibson K, Kaplan J, Lisk L et al (2021) Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 397(10289):2070–2080. https://​doi.​org/​10.​1016/​S0140-6736(21)00578-XCrossRefPubMed
13.
Zurück zum Zitat Rovin BH, Solomons N, Pendergraft WF III, Dooley MA, Tumlin J, Romero-Diaz J, Lysenko L, Navarra SV, Huizinga RB et al (2019) A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis. Kidney Int 95:219–231CrossRefPubMed Rovin BH, Solomons N, Pendergraft WF III, Dooley MA, Tumlin J, Romero-Diaz J, Lysenko L, Navarra SV, Huizinga RB et al (2019) A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis. Kidney Int 95:219–231CrossRefPubMed
15.
Zurück zum Zitat Bao H, Liu Z‑H, Xie H‑L, Hu W‑X, Zhang H‑T et al (2008) Successful treatment of class V+ IV lupus nephritis with multitarget therapy. J Am Soc Nephrol 19(10):2001–2010CrossRefPubMedPubMedCentral Bao H, Liu Z‑H, Xie H‑L, Hu W‑X, Zhang H‑T et al (2008) Successful treatment of class V+ IV lupus nephritis with multitarget therapy. J Am Soc Nephrol 19(10):2001–2010CrossRefPubMedPubMedCentral
16.
18.
Zurück zum Zitat Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151:264–269CrossRefPubMed Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151:264–269CrossRefPubMed
19.
Zurück zum Zitat Brown S, Hutton B, Clifford T, Coyle D, Grima D, Wells G, Cameron C (2014) A Microsoft-Excel-based tool for running and critically appraising network meta-analyses—an overview and application of NetMetaXL. Syst Rev 3:110CrossRefPubMedPubMedCentral Brown S, Hutton B, Clifford T, Coyle D, Grima D, Wells G, Cameron C (2014) A Microsoft-Excel-based tool for running and critically appraising network meta-analyses—an overview and application of NetMetaXL. Syst Rev 3:110CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Caldwell DM, Ades A, Higgins J (2005) Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ 331:897CrossRefPubMedPubMedCentral Caldwell DM, Ades A, Higgins J (2005) Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ 331:897CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Salanti G, Ades A, Ioannidis JP (2011) Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol 64:163–171CrossRefPubMed Salanti G, Ades A, Ioannidis JP (2011) Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol 64:163–171CrossRefPubMed
22.
Zurück zum Zitat Dias S, Welton NJ, Sutton AJ, Caldwell DM, Lu G, Ades A (2013) Evidence synthesis for decision making 4 inconsistency in networks of evidence based on randomized controlled trials. Med Decis Making 33:641–656CrossRefPubMedPubMedCentral Dias S, Welton NJ, Sutton AJ, Caldwell DM, Lu G, Ades A (2013) Evidence synthesis for decision making 4 inconsistency in networks of evidence based on randomized controlled trials. Med Decis Making 33:641–656CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Higgins J, Jackson D, Barrett J, Lu G, Ades A, White I (2012) Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies. Res Synth Methods 3:98–110CrossRefPubMedPubMedCentral Higgins J, Jackson D, Barrett J, Lu G, Ades A, White I (2012) Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies. Res Synth Methods 3:98–110CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Valkenhoef G, Lu G, Brock B, Hillege H, Ades A, Welton NJ (2012) Automating network meta-analysis. Res Synth Methods 3:285–299CrossRefPubMed Valkenhoef G, Lu G, Brock B, Hillege H, Ades A, Welton NJ (2012) Automating network meta-analysis. Res Synth Methods 3:285–299CrossRefPubMed
26.
Zurück zum Zitat Pan L, Lu M‑P, Wang J‑H, Xu M, Yang S‑R (2020) Immunological pathogenesis and treatment of systemic lupus erythematosus. World J Pediatr 16:19–30CrossRefPubMed Pan L, Lu M‑P, Wang J‑H, Xu M, Yang S‑R (2020) Immunological pathogenesis and treatment of systemic lupus erythematosus. World J Pediatr 16:19–30CrossRefPubMed
27.
Zurück zum Zitat Liossis SN, Staveri C (2021) What’s new in the treatment of systemic lupus erythematosus. Front Med 8:221CrossRef Liossis SN, Staveri C (2021) What’s new in the treatment of systemic lupus erythematosus. Front Med 8:221CrossRef
30.
Zurück zum Zitat Mohan S, Radhakrishnan J (2011) Geographical variation in the response of lupus nephritis to mycophenolate mofetil induction therapy. Clin Nephrol 75:233–241CrossRefPubMed Mohan S, Radhakrishnan J (2011) Geographical variation in the response of lupus nephritis to mycophenolate mofetil induction therapy. Clin Nephrol 75:233–241CrossRefPubMed
31.
Zurück zum Zitat Lee YH, Song GG (2019) Causal association between rheumatoid arthritis with the increased risk of type 2 diabetes: a mendelian randomization analysis. J Rheum Dis 26:131–136CrossRef Lee YH, Song GG (2019) Causal association between rheumatoid arthritis with the increased risk of type 2 diabetes: a mendelian randomization analysis. J Rheum Dis 26:131–136CrossRef
32.
Zurück zum Zitat Lee YH, Song GG (2020) Circulating interleukin-18 level in systemic lupus erythematosus. J Rheum Dis 27:110–115CrossRef Lee YH, Song GG (2020) Circulating interleukin-18 level in systemic lupus erythematosus. J Rheum Dis 27:110–115CrossRef
33.
Zurück zum Zitat Lee YH, Song GG (2020) Association between signal transducers and activators of transcription 4 rs7574865 polymorphism and systemic lupus erythematosus: a meta-analysis. J Rheum Dis 27:277–284CrossRef Lee YH, Song GG (2020) Association between signal transducers and activators of transcription 4 rs7574865 polymorphism and systemic lupus erythematosus: a meta-analysis. J Rheum Dis 27:277–284CrossRef
34.
Zurück zum Zitat Lee YH, Song GG (2020) Circulating interleukin-37 levels in rheumatoid arthritis and systemic lupus erythematosus and their correlations with disease activity: a meta-analysis. J Rheum Dis 27:152–158CrossRef Lee YH, Song GG (2020) Circulating interleukin-37 levels in rheumatoid arthritis and systemic lupus erythematosus and their correlations with disease activity: a meta-analysis. J Rheum Dis 27:152–158CrossRef
35.
Zurück zum Zitat Lee YH, Song GG (2020) Associations between circulating Interleukin-17 levels and systemic lupus erythematosus and between Interleukin-17 gene polymorphisms and disease susceptibility: a meta-analysis. J Rheum Dis 27:37–44CrossRef Lee YH, Song GG (2020) Associations between circulating Interleukin-17 levels and systemic lupus erythematosus and between Interleukin-17 gene polymorphisms and disease susceptibility: a meta-analysis. J Rheum Dis 27:37–44CrossRef
Metadaten
Titel
A network meta-analysis of randomized controlled trials comparing the effectiveness and safety of voclosporin or tacrolimus plus mycophenolate mofetil as induction treatment for lupus nephritis
verfasst von
Young Ho Lee, MD, PhD
Gwan Gyu Song
Publikationsdatum
20.09.2021
Verlag
Springer Medizin
Erschienen in
Zeitschrift für Rheumatologie / Ausgabe 7/2023
Print ISSN: 0340-1855
Elektronische ISSN: 1435-1250
DOI
https://doi.org/10.1007/s00393-021-01087-z

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