Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Meta-Analysis

Comparison of Different Uses of Cyclophosphamide in Lupus Nephritis: A Meta-Analysis of Randomized Controlled Trials

Author(s): Yebei Li, Shizhang Xu and Gaosi Xu*

Volume 20, Issue 5, 2020

Page: [687 - 702] Pages: 16

DOI: 10.2174/1871530319666191107110420

Price: $65

Abstract

Background: The present study aims to compare the relative efficacy and safety of different uses of cyclophosphamide (CYC) in lupus nephritis (LN).

Methods: We searched the Cochrane Library, EMBASE, Global Health, MEDLINE and PubMed for articles from the database till June 2018.

Results: 12 randomized controlled trials with 994 participants were included. The meta-analysis indicated that the short-interval lower-dose intravenous CYC regime remarkably reduced 24-hour proteinuria [mean difference (MD) -0.45; 95% confidence interval (CI) -0.62 to -0.27; I2 0%], incidence of major infections [odds ratio (OR) 0.62, 95% CI 0.40 to 0.95; I2 42%], gonadal toxicity (OR 0.41, 95% CI 0.27 to 0.62; I2 0%), and leukopenia (OR 0.55, 95% CI 0.33 to 0.94, I2 0%), while high-dose regime had an obvious lower probability of doubling of serum creatinine (Scr) level (OR 2.43; 95% CI 1.19 to 4.95; I2 0%). However, the difference in the complete and total remission rates between the two regimens was not observed.

Conclusion: The result suggested that the short-interval lower-dose CYC regime remarkably reduced 24-hour proteinuria and the incidence of adverse events, while the long-course high-dose regime played a significant role in reducing the rate of doubling Scr level.

Keywords: Lupus nephritis, cyclophosphamide, randomized controlled trails, proteinuria, serum creatinine, usage.

Graphical Abstract
[1]
Cameron, J.S. Lupus nephritis. J. Am. Soc. Nephrol., 1999, 10(2), 413-424.
[PMID: 10215343]
[2]
Mok, C.C. Understanding lupus nephritis: diagnosis, management, and treatment options. Int. J. Womens Health, 2012, 4, 213-222.
[http://dx.doi.org/10.2147/IJWH.S28034] [PMID: 22675266]
[3]
Mok, C.C.; Kwok, R.C.; Yip, P.S. Effect of renal disease on the standardized mortality ratio and life expectancy of patients with systemic lupus erythematosus. Arthritis Rheum., 2013, 65(8), 2154-2160.
[http://dx.doi.org/10.1002/art.38006] [PMID: 23754671]
[4]
Beimler, J.H.; Andrassy, K. Cyclophosphamide treatment in systemic necrotizing vasculitis and lupus nephritis. How long? How much? Pediatr. Nephrol., 2004, 19(9), 949-955.
[http://dx.doi.org/10.1007/s00467-004-1553-6] [PMID: 15257454]
[5]
Austin, H.A., III; Klippel, J.H.; Balow, J.E.; le Riche, N.G.; Steinberg, A.D.; Plotz, P.H.; Decker, J.L. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N. Engl. J. Med., 1986, 314(10), 614-619.
[http://dx.doi.org/10.1056/NEJM198603063141004] [PMID: 3511372]
[6]
Gourley, M.F.; Austin, H.A., III; Scott, D.; Yarboro, C.H.; Vaughan, E.M.; Muir, J.; Boumpas, D.T.; Klippel, J.H.; Balow, J.E.; Steinberg, A.D. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann. Intern. Med., 1996, 125(7), 549-557.
[http://dx.doi.org/10.7326/0003-4819-125-7-199610010-00003] [PMID: 8815753]
[7]
Illei, G.G.; Austin, H.A.; Crane, M.; Collins, L.; Gourley, M.F.; Yarboro, C.H.; Vaughan, E.M.; Kuroiwa, T.; Danning, C.L.; Steinberg, A.D.; Klippel, J.H.; Balow, J.E.; Boumpas, D.T. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann. Intern. Med., 2001, 135(4), 248-257.
[http://dx.doi.org/10.7326/0003-4819-135-4-200108210-00009] [PMID: 11511139]
[8]
Mok, C.C.; Lau, C.S.; Wong, R.W. Risk factors for ovarian failure in patients with systemic lupus erythematosus receiving cyclophosphamide therapy. Arthritis Rheum., 1998, 41(5), 831-837.
[http://dx.doi.org/10.1002/1529-0131(199805)41:5<831:AID-ART9>3.0.CO;2-1] [PMID: 9588734]
[9]
Tian, M.; Song, X.; Dong, L.; Xin, X.; Dong, J. Systematic evaluation of different doses of cyclophosphamide induction therapy for lupus nephritis. Medicine (Baltimore), 2017, 96(51)e9408
[http://dx.doi.org/10.1097/MD.0000000000009408] [PMID: 29390559]
[10]
Bae, S.C. YH L. Comparative efficacy and safety of low-dose and high-dose cyclophosphamide as induction therapy for lupus nephritis: a network meta-analysis. Z. Rheumatol., 2018, 10http://doi.org/1007/s00393-018-0512-8
[11]
Bertsias, G.K.; Tektonidou, M.; Amoura, Z.; Aringer, M.; Bajema, I.; Berden, J.H.; Boletis, J.; Cervera, R.; Dörner, T.; Doria, A.; Ferrario, F.; Floege, J.; Houssiau, F.A.; Ioannidis, J.P.; Isenberg, D.A.; Kallenberg, C.G.; Lightstone, L.; Marks, S.D.; Martini, A.; Moroni, G.; Neumann, I.; Praga, M.; Schneider, M.; Starra, A.; Tesar, V.; Vasconcelos, C.; van Vollenhoven, R.F.; Zakharova, H.; Haubitz, M.; Gordon, C.; Jayne, D.; Boumpas, D.T. 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., 2012, 71(11), 1771-1782.
[http://dx.doi.org/10.1136/annrheumdis-2012-201940] [PMID: 22851469]
[12]
Higgins, J.P.; Thompson, S.G.; Deeks, J.J.; Altman, D.G. Measuring inconsistency in meta-analyses. BMJ, 2003, 327(7414), 557-560.
[http://dx.doi.org/10.1136/bmj.327.7414.557] [PMID: 12958120]
[13]
Friedrich, J.O.; Adhikari, N.K.J.; Beyene, J. Inclusion of zero total event trials in meta-analyses maintains analytic consistency and incorporates all available data. BMC Med. Res. Methodol., 2007, 7, 5.
[http://dx.doi.org/10.1186/1471-2288-7-5] [PMID: 17244367]
[14]
Boumpas, D.T.; Austin, H.A., III; Vaughn, E.M.; Klippel, J.H.; Steinberg, A.D.; Yarboro, C.H.; Balow, J.E. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet, 1992, 340(8822), 741-745.
[http://dx.doi.org/10.1016/0140-6736(92)92292-N] [PMID: 1356175]
[15]
Houssiau, F.A.; Vasconcelos, C.; D’Cruz, D.; Sebastiani, G.D.; Garrido Ed, Ede.R.; Danieli, M.G.; Abramovicz, D.; Blockmans, D.; Mathieu, A.; Direskeneli, H.; Galeazzi, M.; Gül, A.; Levy, Y.; Petera, P.; Popovic, R.; Petrovic, R.; Sinico, R.A.; Cattaneo, R.; Font, J.; Depresseux, G.; Cosyns, J.P.; Cervera, R. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum., 2002, 46(8), 2121-2131.
[http://dx.doi.org/10.1002/art.10461] [PMID: 12209517]
[16]
Houssiau, F.A.; Vasconcelos, C.; D’Cruz, D.; Sebastiani, G.D.; de Ramon Garrido, E.; Danieli, M.G.; Abramovicz, D.; Blockmans, D.; Mathieu, A.; Direskeneli, H.; Galeazzi, M.; Gül, A.; Levy, Y.; Petera, P.; Popovic, R.; Petrovic, R.; Sinico, R.A.; Cattaneo, R.; Font, J.; Depresseux, G.; Cosyns, J.P.; Cervera, R. Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial. Arthritis Rheum., 2004, 50(12), 3934-3940.
[http://dx.doi.org/10.1002/art.20666] [PMID: 15593207]
[17]
Houssiau, F.A.; Vasconcelos, C.; D’Cruz, D.; Sebastiani, G.D.; de Ramon Garrido, E.; Danieli, M.G.; Abramovicz, D.; Blockmans, D.; Cauli, A.; Direskeneli, H.; Galeazzi, M.; Gül, A.; Levy, Y.; Petera, P.; Popovic, R.; Petrovic, R.; Sinico, R.A.; Cattaneo, R.; Font, J.; Depresseux, G.; Cosyns, J.P.; Cervera, R. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann. Rheum. Dis., 2010, 69(1), 61-64.
[http://dx.doi.org/10.1136/ard.2008.102533] [PMID: 19155235]
[18]
Mehra, S.; Usdadiya, J.B.; Jain, V.K.; Misra, D.P.; Negi, V.S. Comparing the efficacy of low-dose vs high-dose cyclophosphamide regimen as induction therapy in the treatment of proliferative lupus nephritis: a single center study. Rheumatol. Int., 2018, 38(4), 557-568.
[http://dx.doi.org/10.1007/s00296-018-3995-3] [PMID: 29450636]
[19]
Mitwalli, A.H.; Al Wakeel, J.S.; Hurraib, S.; Aisha, A.; Al Suwaida, A.; Alam, A.; Hammad, D.; Sulimani, F.; Memon, N.A.; Askar, A.; Al Tuwaijri, A.; Qudsi, A. Comparison of high and low dose of cyclophosphamide in lupus nephritis patients: a long-term randomized controlled trial. Saudi J. Kidney Dis. Transpl., 2011, 22(5), 935-940.
[PMID: 21912022]
[20]
Sabry, A.; Abo-Zenah, H.; Medhat, T.; Sheashaa, H.; Mahmoud, K.; El-Huseini, A. A comparative study of two intensified pulse cyclophosphamide remission-inducing regimens for diffuse proliferative lupus nephritis: an Egyptian experience. Int. Urol. Nephrol., 2009, 41(1), 153-161.
[http://dx.doi.org/10.1007/s11255-007-9325-4] [PMID: 18214709]
[21]
Sahay, M.; Saivani, Y.; Ismal, K.; Vali, P.S. Mycophenolate versus cyclophosphamide for lupus nephritis. Indian J. Nephrol., 2018, 28(1), 35-40.
[http://dx.doi.org/10.4103/ijn.IJN_2_16] [PMID: 29515299]
[22]
Sun, J.; Zhang, H.; Ji, Y.; Gui, M.; Yi, B.; Wang, J.; Jiang, J. Efficacy and safety of cyclophosphamide combined with mycophenolate mofetil for induction treatment of class IV lupus nephritis. Int. J. Clin. Exp. Med., 2015, 8(11), 21572-21578.
[PMID: 26885107]
[23]
witte T, Schaumann D, Hein R, et al. Cyclophosphamide bolus therapy in lupus nephritis. Dtsch Med Wochenschr,, 1993, 118, 1005-10.
[24]
Yee, C.S.; Gordon, C.; Dostal, C.; Petera, P.; Dadoniene, J.; Griffiths, B.; Rozman, B.; Isenberg, D.A.; Sturfelt, G.; Nived, O.; Turney, J.H.; Venalis, A.; Adu, D.; Smolen, J.S.; Emery, P. EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis. Ann. Rheum. Dis., 2004, 63(5), 525-529.
[http://dx.doi.org/10.1136/ard.2002.003574] [PMID: 15082482]
[25]
Zhang, X.W.; Li, C.; Ma, X.X.; Zhao, J.X.; An, Y.; Liu, S.; Li, Y.; Li, Z.G. Short-interval lower-dose intravenous cyclophosphamide as induction and maintenance therapy for lupus nephritis: a prospective observational study. Clin. Rheumatol., 2014, 33(7), 939-945.
[http://dx.doi.org/10.1007/s10067-014-2590-6] [PMID: 24744152]
[26]
Tan, E.M.; Cohen, A.S.; Fries, J.F.; Masi, A.T.; McShane, D.J.; Rothfield, N.F.; Schaller, J.G.; Talal, N.; Winchester, R.J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum., 1982, 25(11), 1271-1277.
[http://dx.doi.org/10.1002/art.1780251101] [PMID: 7138600]
[27]
Hochberg, M.C. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum., 1997, 40(9), 1725.
[http://dx.doi.org/10.1002/art.1780400928] [PMID: 9324032]
[28]
Hahn, B.H.; McMahon, M.A.; Wilkinson, A.; Wallace, W.D.; Daikh, D.I.; Fitzgerald, J.D.; Karpouzas, G.A.; Merrill, J.T.; Wallace, D.J.; Yazdany, J.; Ramsey-Goldman, R.; Singh, K.; Khalighi, M.; Choi, S.I.; Gogia, M.; Kafaja, S.; Kamgar, M.; Lau, C.; Martin, W.J.; Parikh, S.; Peng, J.; Rastogi, A.; Chen, W.; Grossman, J.M. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res. (Hoboken), 2012, 64(6), 797-808.
[http://dx.doi.org/10.1002/acr.21664] [PMID: 22556106]
[29]
Weening, J.J.; D’Agati, V.D.; Schwartz, M.M.; Seshan, S.V.; Alpers, C.E.; Appel, G.B.; Balow, J.E.; Bruijn, J.A.; Cook, T.; Ferrario, F.; Fogo, A.B.; Ginzler, E.M.; Hebert, L.; Hill, G.; Hill, P.; Jennette, J.C.; Kong, N.C.; Lesavre, P.; Lockshin, M.; Looi, L.M.; Makino, H.; Moura, L.A.; Nagata, M. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J. Am. Soc. Nephrol., 2004, 15(2), 241-250.
[http://dx.doi.org/10.1097/01.ASN.0000108969.21691.5D] [PMID: 14747370]
[30]
Houssiau, F.A. Cyclophosphamide in lupus nephritis. Lupus, 2005, 14(1), 53-58.
[http://dx.doi.org/10.1191/0961203305lu2060oa] [PMID: 15732289]
[31]
Bomback, A.S.; Appel, G.B. Updates on the treatment of lupus nephritis. J. Am. Soc. Nephrol., 2010, 21(12), 2028-2035.
[http://dx.doi.org/10.1681/ASN.2010050472] [PMID: 21051743]
[32]
Lee, Y.H.; Woo, J.H.; Choi, S.J.; Ji, J.D.; Song, G.G. Induction and maintenance therapy for lupus nephritis: a systematic review and meta-analysis. Lupus, 2010, 19(6), 703-710.
[http://dx.doi.org/10.1177/0961203309357763] [PMID: 20064907]
[33]
Martin-Suarez, I.; D’Cruz, D.; Mansoor, M.; Fernandes, A.P.; Khamashta, M.A.; Hughes, G.R. Immunosuppressive treatment in severe connective tissue diseases: effects of low dose intravenous cyclophosphamide. Ann. Rheum. Dis., 1997, 56(8), 481-487.
[http://dx.doi.org/10.1136/ard.56.8.481] [PMID: 9306871]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy