Skip to main content
main-content
Erschienen in: Zeitschrift für Rheumatologie 5/2019

23.07.2018 | Originalien

Comparative efficacy and safety of low-dose and high-dose cyclophosphamide as induction therapy for lupus nephritis: a network meta-analysis

verfasst von: S.-C. Bae, MD, PhD Y. H. Lee

Erschienen in: Zeitschrift für Rheumatologie | Ausgabe 5/2019

Einloggen, um Zugang zu erhalten

Abstract

Aim

To assess the relative efficacy and safety of low-dose cyclophosphamide (LCYC) and high-dose CYC (HCYC) as induction therapy for lupus nephritis.

Methods

Bayesian random-effects network meta-analysis was performed to combine direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of LCYC, HCYC, and mycophenolate mofetil (MMF) for induction therapy in patients with lupus nephritis.

Results

Eleven RCTs (1212 patients) were included. MMF and LCYC showed similar overall response rates (OR 1.02, 95% credible interval [CrI] 0.51–2.02), and MMF showed a higher efficacy than HCYC (OR 1.48, 95% CrI 0.99–2.44). Similarly, LCYC showed a higher overall response than HCYC (OR 1.46, 95% CrI 0.83–2.86). Ranking probability based on SUCRA (surface under the cumulative ranking curve) indicated that MMF had the highest probability of being the best treatment for achieving an overall response (SUCRA = 0.7461), followed by LCYC (SUCRA = 0.6978) and HCYC (SUCRA = 0.0561). LCYC showed the highest probability of decreasing the risk of serious infections (SUCRA = 0.8513), followed by MMF (SUCRA = 0.49387) and HCYC (SUCRA = 0.1548).

Conclusion

LCYC was an efficacious induction treatment for patients with lupus nephritis and had the highest probability of decreasing the risk of serious infections. Higher response rates and a more favorable safety profile suggest that LCYC is a good option for induction treatment in these patients.
Literatur
1.
Zurück zum Zitat Waldman M, Appel GB (2006) Update on the treatment of lupus nephritis. Kidney Int 70:1403–1412 CrossRef Waldman M, Appel GB (2006) Update on the treatment of lupus nephritis. Kidney Int 70:1403–1412 CrossRef
2.
Zurück zum Zitat Ahn S‑H, Jung JH (2017) Renal involvement in rheumatic diseases. J Rheum Dis 24:174–184 CrossRef Ahn S‑H, Jung JH (2017) Renal involvement in rheumatic diseases. J Rheum Dis 24:174–184 CrossRef
3.
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 25:47–55 CrossRef 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 25:47–55 CrossRef
4.
Zurück zum Zitat Austin HA III, Klippel JH, Balow JE, Le Riche NG, Steinberg AD, Plotz PH, Decker JL (1986) Therapy of lupus nephritis. N Engl J Med 314:614–619 CrossRef Austin HA III, Klippel JH, Balow JE, Le Riche NG, Steinberg AD, Plotz PH, Decker JL (1986) Therapy of lupus nephritis. N Engl J Med 314:614–619 CrossRef
5.
Zurück zum Zitat Petri M (2004) Cyclophosphamide: new approaches for systemic lupus erythematosus. Lupus 13:366–371 CrossRef Petri M (2004) Cyclophosphamide: new approaches for systemic lupus erythematosus. Lupus 13:366–371 CrossRef
6.
Zurück zum Zitat Houssiau FA, Vasconcelos C, D’Cruz D et al (2002) Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 46:2121–2131 CrossRef Houssiau FA, Vasconcelos C, D’Cruz D et al (2002) Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 46:2121–2131 CrossRef
7.
Zurück zum Zitat Sabry A, Abo-Zenah H, Medhat T, Sheashaa H, Mahmoud K, El-Huseini A (2009) A comparative study of two intensified pulse cyclophosphamide remission-inducing regimens for diffuse proliferative lupus nephritis: an Egyptian experience. Int Urol Nephrol 41:153–161 CrossRef Sabry A, Abo-Zenah H, Medhat T, Sheashaa H, Mahmoud K, El-Huseini A (2009) A comparative study of two intensified pulse cyclophosphamide remission-inducing regimens for diffuse proliferative lupus nephritis: an Egyptian experience. Int Urol Nephrol 41:153–161 CrossRef
8.
Zurück zum Zitat Rathi M, Goyal A, Jaryal A et al (2016) Comparison of low-dose intravenous cyclophosphamide with oral mycophenolate mofetil in the treatment of lupus nephritis. Kidney Int 89:235–242 CrossRef Rathi M, Goyal A, Jaryal A et al (2016) Comparison of low-dose intravenous cyclophosphamide with oral mycophenolate mofetil in the treatment of lupus nephritis. Kidney Int 89:235–242 CrossRef
9.
Zurück zum Zitat Zhang XW, Li C, Ma XX, Zhao JX, An Y, Liu S, Li Y, Li ZG (2014) Short-interval lower-dose intravenous cyclophosphamide as induction and maintenance therapy for lupus nephritis: a prospective observational study. Clin Rheumatol 33:939–945 CrossRef Zhang XW, Li C, Ma XX, Zhao JX, An Y, Liu S, Li Y, Li ZG (2014) Short-interval lower-dose intravenous cyclophosphamide as induction and maintenance therapy for lupus nephritis: a prospective observational study. Clin Rheumatol 33:939–945 CrossRef
10.
Zurück zum Zitat Catalá-López F, Tobías A, Cameron C, Moher D, Hutton B (2014) Network meta-analysis for comparing treatment effects of multiple interventions: an introduction. Rheumatol Int 34:1489–1496 CrossRef Catalá-López F, Tobías A, Cameron C, Moher D, Hutton B (2014) Network meta-analysis for comparing treatment effects of multiple interventions: an introduction. Rheumatol Int 34:1489–1496 CrossRef
11.
Zurück zum Zitat Caldwell DM, Ades A, Higgins J (2005) Simultaneous comparison of multiple treatments: combining direct and indirect evidence. Br Med J 331:897 CrossRef Caldwell DM, Ades A, Higgins J (2005) Simultaneous comparison of multiple treatments: combining direct and indirect evidence. Br Med J 331:897 CrossRef
12.
Zurück zum Zitat Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12 CrossRef Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12 CrossRef
13.
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 151:264–269 CrossRef Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151:264–269 CrossRef
14.
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 3:110 CrossRef 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 3:110 CrossRef
15.
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 64:163–171 CrossRef 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 64:163–171 CrossRef
16.
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 33:641–656 CrossRef 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 33:641–656 CrossRef
17.
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 3:98–110 CrossRef 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 3:98–110 CrossRef
18.
Zurück zum Zitat Valkenhoef G, Lu G, Brock B, Hillege H, Ades A, Welton NJ (2012) Automating network meta-analysis. Res Synth Methods 3:285–299 CrossRef Valkenhoef G, Lu G, Brock B, Hillege H, Ades A, Welton NJ (2012) Automating network meta-analysis. Res Synth Methods 3:285–299 CrossRef
19.
Zurück zum Zitat Feng X, Gu F, Chen W, Liu Y, Wei H, Liu L, Yin S, Da Z, Sun L (2014) Mizoribine versus mycophenolate mofetil or intravenous cyclophosphamide for induction treatment of active lupus nephritis. Chin Med J 127:3718–3723 PubMed Feng X, Gu F, Chen W, Liu Y, Wei H, Liu L, Yin S, Da Z, Sun L (2014) Mizoribine versus mycophenolate mofetil or intravenous cyclophosphamide for induction treatment of active lupus nephritis. Chin Med J 127:3718–3723 PubMed
20.
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 27:1467–1472 CrossRef 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 27:1467–1472 CrossRef
21.
Zurück zum Zitat El-Shafey EM, Abdou SH, Shareef MM (2010) Is mycophenolate mofetil superior to pulse intravenous cyclophosphamide for induction therapy of proliferative lupus nephritis in Egyptian patients? Clin Exp Nephrol 14:214–221 CrossRef El-Shafey EM, Abdou SH, Shareef MM (2010) Is mycophenolate mofetil superior to pulse intravenous cyclophosphamide for induction therapy of proliferative lupus nephritis in Egyptian patients? Clin Exp Nephrol 14:214–221 CrossRef
22.
Zurück zum Zitat Appel GB, Contreras G, Dooley MA et al (2009) Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 20:1103–1112 CrossRef Appel GB, Contreras G, Dooley MA et al (2009) Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 20:1103–1112 CrossRef
23.
Zurück zum Zitat Wang J, Hu W, Xie H, Zhang H, Chen H, Zeng C, Liu Z, Li L (2007) Induction therapies for class IV lupus nephritis with non-inflammatory necrotizing vasculopathy: mycophenolate mofetil or intravenous cyclophosphamide. Lupus 16:707–712 CrossRef Wang J, Hu W, Xie H, Zhang H, Chen H, Zeng C, Liu Z, Li L (2007) Induction therapies for class IV lupus nephritis with non-inflammatory necrotizing vasculopathy: mycophenolate mofetil or intravenous cyclophosphamide. Lupus 16:707–712 CrossRef
24.
Zurück zum Zitat Ong LM, Hooi LS, Lim TO, Goh BL, Ahmad G, Ghazalli R, Teo SM, Wong HS, Tan SY, Shaariah W (2005) Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis. Nephrology 10:504–510 CrossRef Ong LM, Hooi LS, Lim TO, Goh BL, Ahmad G, Ghazalli R, Teo SM, Wong HS, Tan SY, Shaariah W (2005) Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis. Nephrology 10:504–510 CrossRef
25.
Zurück zum Zitat Ginzler EM, Dooley MA, Aranow C et al (2005) Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 353:2219–2228 CrossRef Ginzler EM, Dooley MA, Aranow C et al (2005) Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 353:2219–2228 CrossRef
26.
Zurück zum Zitat Mohan S, Radhakrishnan J (2011) Geographical variation in the response of lupus nephritis to mycophenolate mofetil induction therapy. Clin Nephrol 75:233–241 CrossRef Mohan S, Radhakrishnan J (2011) Geographical variation in the response of lupus nephritis to mycophenolate mofetil induction therapy. Clin Nephrol 75:233–241 CrossRef
27.
Zurück zum Zitat Lee Y‑H, Bae S‑C, Song G‑G (2012) Omega-3 polyunsaturated fatty acids and the treatment of rheumatoid arthritis: a meta-analysis. Arch Med Res 43:356–362 CrossRef Lee Y‑H, Bae S‑C, Song G‑G (2012) Omega-3 polyunsaturated fatty acids and the treatment of rheumatoid arthritis: a meta-analysis. Arch Med Res 43:356–362 CrossRef
28.
Zurück zum Zitat Lee YH, Bae SC, Song GG (2013) Hepatitis B virus (HBV) reactivation in rheumatic patients with hepatitis core antigen (HBV occult carriers) undergoing anti-tumor necrosis factor therapy. Clin Exp Rheumatol 23:118–121 Lee YH, Bae SC, Song GG (2013) Hepatitis B virus (HBV) reactivation in rheumatic patients with hepatitis core antigen (HBV occult carriers) undergoing anti-tumor necrosis factor therapy. Clin Exp Rheumatol 23:118–121
Metadaten
Titel
Comparative efficacy and safety of low-dose and high-dose cyclophosphamide as induction therapy for lupus nephritis: a network meta-analysis
verfasst von
S.-C. Bae
MD, PhD Y. H. Lee
Publikationsdatum
23.07.2018
Verlag
Springer Medizin
Erschienen in
Zeitschrift für Rheumatologie / Ausgabe 5/2019
Print ISSN: 0340-1855
Elektronische ISSN: 1435-1250
DOI
https://doi.org/10.1007/s00393-018-0512-8

Weitere Artikel der Ausgabe 5/2019

Zeitschrift für Rheumatologie 5/2019 Zur Ausgabe

Mitteilungen der DGRh

Mitteilungen der DGRh

Mitteilungen der DRL

Mitteilungen der DRL

Update Rheumatologie

Spondyloarthritiden II

Neu im Fachgebiet Innere Medizin

Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.