Lupus nephritis
Experience with reduced doses of glucocorticoids in a unit of systemic autoimmune diseases
DOI:
https://doi.org/10.29193/RMU.37.4.6Keywords:
LUPUS NEPHRITIS, GLUCOCORTICOIDS, PREDNISONEAbstract
Introduction: current recommendations for the treatment of lupus nephritis (LN) point to glucocorticoid doses lower to achieve disease control and prevent accumulated damage.
Objective: to know and compare the response to treatment of patients with proliferative LN in its induction stage with two Prednisone treatment regimens (PDN): reduced initial doses <30 mg / d and standard initial doses> 30 mg / d.
Method: clinical, analytical and therapeutic variables of patients with proliferative LN categorized in two were compared groups according to standard or reduced prednisone starting dose (PDNi).
Results: 21 patients with proliferative LN were studied (n = 12 reduced PDNi vs. n = 9 standard PDNi). There were no significant differences in the clinical and analytical variables. A statistically significant difference was observed in the number of methylprednisolone pulses (5 ± 2.95 PDNi <30 mg / d vs 2.33 ± 2.91 PDNi> 30 mg / d, p = 0.041) and in the dose of prednisone accumulated at 6 months (12.8 mg ± 4.9 PDNi <30 mg / d vs 30.0 ± 13.1 mg PDNi> 30 mg / d, p = 0.008). There were no differences significant in the proportion of patients who achieved the complete response, in the time to reach it or in the adverse effects between both groups.
Conclusions: the therapeutic scheme of the PDNi group <30 mg / d was associated with a lower accumulated dose of prednisone and a response to comparable treatment, which suggests less accumulated damage related to the use of glucocorticoids.
References
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26) Ruiz-Irastorza G, Ugarte A, Saint-Pastou Terrier C, Lazaro E, Iza A, Couzi L, et al. Repeated pulses of methyl-prednisolone with reduced doses of prednisone improve the outcome of class III, IV and V lupus nephritis: An observational comparative study of the Lupus-Cruces and lupus-Bordeaux cohorts. Autoimmun Rev 2017; 16(8):826-32.
27) Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40(9):1725. doi: 10.1002/art.1780400928.
28) Weening J, D’Agati V, Schwartz M, Seshan S, Alpers C, Appel G, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004; 15(2):241-50. doi: 10.1097/01.asn.0000108969.21691.5d.
29) Montañés Bermúdez R, Bover Sanjuán J, Oliver Samper A, Ballarín Castán J, Gràcia García S. Valoración de la nueva ecuación CKD-EPI para la estimación del filtrado glomerular. Nefrología (Madr.) 2010; 30(2):185-94.
30) Houssiau F, Vasconcelos C, D’Cruz D, Sebastiani G, Garrido Ed R, Danieli M, et al. 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):2121-31.
31) Gladman D, Ibañez D, Urowitz M. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002; 29(2):288-91.
32) Osakidetza. Servicio Vasco de Salud. Hospital Universitario Cruces. Servicio de Medicina Interna, Unidad de Enfermedades Autoinmunes. Autoinmunes. Mobile Application Version 1.05. Osakidetza: Hospital Universitario Cruces, 2019. Disponible en: https://play.google.com/store/apps/details?id=com.ionicframework.apautoinmunes2327096&hl=es&gl=US. [Consulta: 15 setiembre 2020].
33) Tarr T, Papp G, Nagy N, Cserép E, Zeher M. Chronic high-dose glucocorticoid therapy triggers the development of chronic organ damage and worsens disease outcome in systemic lupus erythematosus. Clin Rheumatol 2017; 36(2):327-33.
34) Ruiz-Irastorza G, Danza A, Khamashta M. Tratamiento del lupus eritematoso sistémico: mitos, certezas y dudas. Med Clin (Barc) 2013; 141(12):533-42.
35) Little J, Parker B, Lunt M, Hanly J, Urowitz M, Clarke A, et al. Glucocorticoid use and factors associated with variability in this use in the Systemic Lupus International Collaborating Clinics Inception Cohort. Rheumatology (Oxford) 2018; 57(4):677-87.
36) Ruiz-Arruza I, Lozano J, Cabezas-Rodríguez I, Medina J, Ugarte A, Erdozain J, et al. Restrictive use of oral glucocorticoids in systemic lupus erythematosus and prevention of damage without worsening long-term disease control: an observational study. Arthritis Care Res (Hoboken) 2018; 70(4):582-91.
37) Petri M, Purvey S, Fang H, Magder L. Predictors of organ damage in systemic lupus erythematosus: the Hopkins Lupus Cohort. Arthritis Rheum 2012; 64(12):4021-8.
38) Cassano G, Roverano S, Paira S, Bellomio V, Lucero E, Berman A, et al. Accrual of organ damage over time in Argentine patients with systemic lupus erythematosus: a multi-centre study. Clin Rheumatol 2007; 26(12):2017-22.
39) Buttgereit F, Wehling M, Burmester G. A new hypothesis of modular glucocorticoid actions: steroid treatment of rheumatic diseases revisited. Arthritis Rheum 1998; 41(5):761-7.
40) Mejía-Vilet J, Ayoub I. The use of glucocorticoids in lupus nephritis: new pathways for an old drug. Front Med (Lausanne) 2021; 8:622225. doi: 10.3389/fmed.2021.622225
41) Buttgereit F, Straub R, Wehling M, Burmester G. Glucocorticoids in the treatment of rheumatic diseases: an update on the mechanisms of action. Arthritis Rheum 2004; 50(11):3408-17.
42) Panettieri R, Schaafsma D, Amrani Y, Koziol-White C, Ostrom R, Tliba O. Non-genomic effects of glucocorticoids: an updated view. Trends Pharmacol Sci 2019; 40(1):38-49.
43) Badsha H, Edwards C. Intravenous pulses of methylprednisolone for systemic lupus erythematosus. Semin Arthritis Rheum 2003; 32(6):370-7.
44) Parker B, Bruce I. High dose methylprednisolone therapy for the treatment of severe systemic lupus erythematosus. Lupus 2007; 16(6):387-93.
45) Ruiz-Irastorza G, Ruiz-Estevez B, Lazaro E, Ruiz-Arruza I, Duffau P, Martin-Cascon M, et al. Prolonged remission in SLE is possible by using reduced doses of prednisone: An observational study from the Lupus-Cruces and Lupus-Bordeaux inception cohorts. Autoimmun Rev 2019; 18(9):102359. doi: 10.1016/j.autrev.2019.102359.
46) Zeher M, Doria A, Lan J, Aroca G, Jayne D, Boletis I, et al. Efficacy and safety of enteric-coated mycophenolate sodium in combination with two glucocorticoid regimens for the treatment of active lupus nephritis. Lupus 2011; 20(14):1484-93.
47) Rovin B, Solomons N, Pendergraft W3rd, Dooley M, Tumlin J, Romero-Diaz J, et al. 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 2019; 95(1):219-31.
48) Sinclair A, Appel G, Dooley M, Ginzler E, Isenberg D, Jayne D, et al. Mycophenolate mofetil as induction and maintenance therapy for lupus nephritis: rationale and protocol for the randomized, controlled Aspreva Lupus Management Study (ALMS). Lupus 2007; 16(12):972-80.
49) Condon M, Ashby D, Pepper R, Cook H, Levy J, Griffith M, et al. Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann Rheum Dis 2013; 72(8):1280-6.
50) Lightstone L, Doria A, Wilson H, Ward F, Larosa M, Bargman J. Can we manage lupus nephritis without chronic corticosteroids administration? Autoimmun Rev 2018; 17(1):4-10. doi: 10.1016/j.autrev.2017.11.002
2) Cervera R, Khamashta M, Font J, Sebastiani G, Gil A, Lavilla P, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 2003; 82(5):299-308.
3) Pons-Estel G, Catoggio L, Cardiel M, Bonfa E, Caeiro F, Sato E, et al. Lupus in Latin-American patients: lessons from the GLADEL cohort. Lupus 2015; 24(6):536-45.
4) Alarcón G. Cohortes multiétnicas de lupus: ¿qué nos han enseñado? Reumatol Clin 2011; 7(1):3-6. doi: 10.1016/j.reuma.2010.11.001.
5) Burgos P, McGwin GJr, Pons-Estel G, Reveille J, Alarcón G, Vilá L. US patients of Hispanic and African ancestry develop lupus nephritis early in the disease course: data from LUMINA, a multiethnic US cohort (LUMINA LXXIV). Ann Rheum Dis 2011; 70(2):393-4.
6) Contreras G, Lenz O, Pardo V, Borja E, Cely C, Iqbal K, et al. Outcomes in African Americans and Hispanics with lupus nephritis. Kidney Int 2006; 69(10):1846-51.
7) Garau M, Cabrera J. Informe del Registro Uruguayo de Glomerulopatías 2018: datos de los años 2016-2017. Montevideo: Programa de Prevención y Tratamiento de las Glomerulopatías, 2018. Disponible en: https://www.nefrologia.hc.edu.uy/images/RUG_Informe2018_1.pdf. [Consulta: 12 abril 2021].
8) Garau M, Cabrera J, Ottati G, Caorsi H, González Martínez F, Acosta N, et al. Temporal trends in biopsy proven glomerular disease in Uruguay, 1990-2014. PLoS One 2018; 13(10):e0206637. doi: 10.1371/journal.pone.0206637.
9) Urowitz M, Gladman D, Tom B, Ibañez D, Farewell V. Changing patterns in mortality and disease outcomes for patients with systemic lupus erythematosus. J Rheumatol 2008; 35(11):2152-8.
10) Thamer M, Hernán M, Zhang Y, Cotter D, Petri M. Prednisone, lupus activity, and permanent organ damage. J Rheumatol 2009; 36(3):560-4.
11) Ruiz-Irastorza G, Danza A, Khamashta M. Glucocorticoid use and abuse in SLE. Rheumatology (Oxford) 2012; 51(7):1145-53.
12) Al Sawah S, Zhang X, Zhu B, Magder L, Foster S, Iikuni N, et al. Effect of corticosteroid use by dose on the risk of developing organ damage over time in systemic lupus erythematosus-the Hopkins Lupus Cohort. Lupus Sci Med 2015; 2(1):e000066. doi: 10.1136/lupus-2014-000066.
13) Apostolopoulos D, Morand E. It hasn’t gone away: the problem of glucocorticoid use in lupus remains. Rheumatology (Oxford) 2017; 56(Suppl 1):i114-22. doi: 10.1093/rheumatology/kew406.
14) Tani C, Vagelli R, Stagnaro C, Carli L, Mosca M. Remission and low disease activity in systemic lupus erythematosus: an achievable goal even with fewer steroids? Real-life data from a monocentric cohort. Lupus Sci Med 2018; 5(1):e000234. doi: 10.1136/lupus-2017-000234.
15) Petri M, Magder L. Comparison of remission and lupus low disease activity state in damage prevention in a united states systemic lupus erythematosus cohort. Arthritis Rheumatol 2018; 70(11):1790-5.
16) Fanouriakis A, Kostopoulou M, Cheema K, Anders H, Aringer M, Bajema I, et al. 2019 Update of the Joint European League against rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis 2020; 79(6):713-23.
17) Ruiz-Arruza I, Ugarte A, Cabezas-Rodríguez I, Medina J, Moran M, Ruiz-Irastorza G. Glucocorticoids and irreversible damage in patients with systemic lupus erythematosus. Rheumatology (Oxford) 2014; 53(8):1470-6.
18) Danza A, Narváez J, Graña D, Pérez L, Viera A, Baccelli A, et al. Relación entre el uso de glucocorticoides y el daño crónico en Lupus Eritematoso Sistémico: una asociación precoz y nociva. Estudio exploratorio. Rev Urug Med Int 2021; 6(1):14-23.
19) Ruiz-Irastorza G, García M, Espinosa G, Caminal L, Mitjavila F, González-León R, et al. First month prednisone dose predicts prednisone burden during the following 11 months: an observational study from the RELES cohort. Lupus Sci Med 2016; 3(1):e000153. doi: 10.1136/lupus-2016-000153.
20) Dixon W, Suissa S, Hudson M. The association between systemic glucocorticoid therapy and the risk of infection in patients with rheumatoid arthritis: systematic review and meta-analyses. Arthritis Res Ther 2011; 13(4):R139. doi: 10.1186/ar3453.
21) George M, Baker J, Winthrop K, Hsu J, Wu Q, Chen L, et al. Risk for serious infection with low-dose glucocorticoids in patients with rheumatoid arthritis: a cohort study. Ann Intern Med 2020; 173(11):870-8.
22) Youssef J, Novosad S, Winthrop K. Infection risk and safety of corticosteroid use. Rheum Dis Clin North Am 2016; 42(1):157-76. doi: 10.1016/j.rdc.2015.08.004.
23) Jick S, Lieberman E, Rahman M, Choi H. Glucocorticoid use, other associated factors, and the risk of tuberculosis. Arthritis Rheum 2006; 55(1):19-26.
24) World Health Organization. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. Geneva: WHO, 2018. Disponible en: https://www.ncbi.nlm.nih.gov/books/NBK531235/pdf/Book shelf_NBK531235.pdf. [Consulta: 26 setiembre 2020].
25) Danza A, Ruiz-Irastorza G. Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies. Lupus 2013; 22(12):1286-94.
26) Ruiz-Irastorza G, Ugarte A, Saint-Pastou Terrier C, Lazaro E, Iza A, Couzi L, et al. Repeated pulses of methyl-prednisolone with reduced doses of prednisone improve the outcome of class III, IV and V lupus nephritis: An observational comparative study of the Lupus-Cruces and lupus-Bordeaux cohorts. Autoimmun Rev 2017; 16(8):826-32.
27) Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40(9):1725. doi: 10.1002/art.1780400928.
28) Weening J, D’Agati V, Schwartz M, Seshan S, Alpers C, Appel G, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004; 15(2):241-50. doi: 10.1097/01.asn.0000108969.21691.5d.
29) Montañés Bermúdez R, Bover Sanjuán J, Oliver Samper A, Ballarín Castán J, Gràcia García S. Valoración de la nueva ecuación CKD-EPI para la estimación del filtrado glomerular. Nefrología (Madr.) 2010; 30(2):185-94.
30) Houssiau F, Vasconcelos C, D’Cruz D, Sebastiani G, Garrido Ed R, Danieli M, et al. 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):2121-31.
31) Gladman D, Ibañez D, Urowitz M. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002; 29(2):288-91.
32) Osakidetza. Servicio Vasco de Salud. Hospital Universitario Cruces. Servicio de Medicina Interna, Unidad de Enfermedades Autoinmunes. Autoinmunes. Mobile Application Version 1.05. Osakidetza: Hospital Universitario Cruces, 2019. Disponible en: https://play.google.com/store/apps/details?id=com.ionicframework.apautoinmunes2327096&hl=es&gl=US. [Consulta: 15 setiembre 2020].
33) Tarr T, Papp G, Nagy N, Cserép E, Zeher M. Chronic high-dose glucocorticoid therapy triggers the development of chronic organ damage and worsens disease outcome in systemic lupus erythematosus. Clin Rheumatol 2017; 36(2):327-33.
34) Ruiz-Irastorza G, Danza A, Khamashta M. Tratamiento del lupus eritematoso sistémico: mitos, certezas y dudas. Med Clin (Barc) 2013; 141(12):533-42.
35) Little J, Parker B, Lunt M, Hanly J, Urowitz M, Clarke A, et al. Glucocorticoid use and factors associated with variability in this use in the Systemic Lupus International Collaborating Clinics Inception Cohort. Rheumatology (Oxford) 2018; 57(4):677-87.
36) Ruiz-Arruza I, Lozano J, Cabezas-Rodríguez I, Medina J, Ugarte A, Erdozain J, et al. Restrictive use of oral glucocorticoids in systemic lupus erythematosus and prevention of damage without worsening long-term disease control: an observational study. Arthritis Care Res (Hoboken) 2018; 70(4):582-91.
37) Petri M, Purvey S, Fang H, Magder L. Predictors of organ damage in systemic lupus erythematosus: the Hopkins Lupus Cohort. Arthritis Rheum 2012; 64(12):4021-8.
38) Cassano G, Roverano S, Paira S, Bellomio V, Lucero E, Berman A, et al. Accrual of organ damage over time in Argentine patients with systemic lupus erythematosus: a multi-centre study. Clin Rheumatol 2007; 26(12):2017-22.
39) Buttgereit F, Wehling M, Burmester G. A new hypothesis of modular glucocorticoid actions: steroid treatment of rheumatic diseases revisited. Arthritis Rheum 1998; 41(5):761-7.
40) Mejía-Vilet J, Ayoub I. The use of glucocorticoids in lupus nephritis: new pathways for an old drug. Front Med (Lausanne) 2021; 8:622225. doi: 10.3389/fmed.2021.622225
41) Buttgereit F, Straub R, Wehling M, Burmester G. Glucocorticoids in the treatment of rheumatic diseases: an update on the mechanisms of action. Arthritis Rheum 2004; 50(11):3408-17.
42) Panettieri R, Schaafsma D, Amrani Y, Koziol-White C, Ostrom R, Tliba O. Non-genomic effects of glucocorticoids: an updated view. Trends Pharmacol Sci 2019; 40(1):38-49.
43) Badsha H, Edwards C. Intravenous pulses of methylprednisolone for systemic lupus erythematosus. Semin Arthritis Rheum 2003; 32(6):370-7.
44) Parker B, Bruce I. High dose methylprednisolone therapy for the treatment of severe systemic lupus erythematosus. Lupus 2007; 16(6):387-93.
45) Ruiz-Irastorza G, Ruiz-Estevez B, Lazaro E, Ruiz-Arruza I, Duffau P, Martin-Cascon M, et al. Prolonged remission in SLE is possible by using reduced doses of prednisone: An observational study from the Lupus-Cruces and Lupus-Bordeaux inception cohorts. Autoimmun Rev 2019; 18(9):102359. doi: 10.1016/j.autrev.2019.102359.
46) Zeher M, Doria A, Lan J, Aroca G, Jayne D, Boletis I, et al. Efficacy and safety of enteric-coated mycophenolate sodium in combination with two glucocorticoid regimens for the treatment of active lupus nephritis. Lupus 2011; 20(14):1484-93.
47) Rovin B, Solomons N, Pendergraft W3rd, Dooley M, Tumlin J, Romero-Diaz J, et al. 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 2019; 95(1):219-31.
48) Sinclair A, Appel G, Dooley M, Ginzler E, Isenberg D, Jayne D, et al. Mycophenolate mofetil as induction and maintenance therapy for lupus nephritis: rationale and protocol for the randomized, controlled Aspreva Lupus Management Study (ALMS). Lupus 2007; 16(12):972-80.
49) Condon M, Ashby D, Pepper R, Cook H, Levy J, Griffith M, et al. Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann Rheum Dis 2013; 72(8):1280-6.
50) Lightstone L, Doria A, Wilson H, Ward F, Larosa M, Bargman J. Can we manage lupus nephritis without chronic corticosteroids administration? Autoimmun Rev 2018; 17(1):4-10. doi: 10.1016/j.autrev.2017.11.002
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2021-11-08
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Carlomagno A, Silveira G, Danza Álvaro, Pizzarossa AC, Yandián M, Yandián F, et al. Lupus nephritis: Experience with reduced doses of glucocorticoids in a unit of systemic autoimmune diseases. Rev. Méd. Urug. [Internet]. 2021 Nov. 8 [cited 2024 Nov. 21];37(4):e37407. Available from: https://revista.rmu.org.uy/index.php/rmu/article/view/756
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