Skip to main content
Top
Published in: Pediatric Nephrology 5/2012

01-05-2012 | Review

New developments in the treatment of systemic lupus erythematosus

Author: Kjell Tullus

Published in: Pediatric Nephrology | Issue 5/2012

Login to get access

Abstract

A large number of new studies on the treatment of systemic lupus erythematosus (SLE) have recently been or are about to be published. Unfortunately, all these studies have been performed in adult patients and there are no studies in children. There is, however, a strong need for more effective drugs with, if possible, fewer side-effects also in children. We do thus need to carefully asses the studies in adult patients to evaluate which of the new drugs can be tried in children with severe lupus nephritis. Some of the new studies have been largely confirmatory, such as demonstrating the efficacy of mycophenolate mofetil in the treatment of SLE, but others have been surprising, such as the lack of efficacy of rituximab. The debate as to why the rituximab studies got negative results is ongoing. Lastly, there is an emergence of novel medications for the treatment of SLE, mostly monoclonal antibodies targeting various aspects of the immune system: belimumab, an antibody affecting B-cell function, is likely to become the first new drug registered for lupus for many years as several large randomized studies have shown significant (albeit not dramatic) responses to this antibody. Many other drugs are in the pipeline and will hopefully come to the clinical arena. This review aims to give a critical appraisal of the plethora of studies in the context of the clinical reality of a pediatric nephrologist treating patients with SLE.
Literature
1.
go back to reference Zetterstrom R, Berglund G (1956) Systemic lupus erythematosus in childhood; a clinical study. Acta Paediatr 45:189–204PubMedCrossRef Zetterstrom R, Berglund G (1956) Systemic lupus erythematosus in childhood; a clinical study. Acta Paediatr 45:189–204PubMedCrossRef
2.
3.
go back to reference Hagelberg S, Lee Y, Bargman J, Mah G, Schneider R, Laskin C, Eddy A, Gladman D, Urowitz M, Hebert D, Silverman E (2002) Long-term follow-up of childhood lupus nephritis. J Rheumatol 29:2635–2642PubMed Hagelberg S, Lee Y, Bargman J, Mah G, Schneider R, Laskin C, Eddy A, Gladman D, Urowitz M, Hebert D, Silverman E (2002) Long-term follow-up of childhood lupus nephritis. J Rheumatol 29:2635–2642PubMed
4.
go back to reference Chan TM, Li FK, Tang CS, Wong RW, Fang GX, Ji YL, Lau CS, Wong AK, Tong MK, Chan KW, Lai KN (2000) Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med 343:1156–1162PubMedCrossRef Chan TM, Li FK, Tang CS, Wong RW, Fang GX, Ji YL, Lau CS, Wong AK, Tong MK, Chan KW, Lai KN (2000) Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med 343:1156–1162PubMedCrossRef
5.
go back to reference Contreras G, Pardo V, Leclercq B, Lenz O, Tozman E, O’Nan P, Roth D (2004) Sequential therapies for proliferative lupus nephritis. N Engl J Med 350:971–980PubMedCrossRef Contreras G, Pardo V, Leclercq B, Lenz O, Tozman E, O’Nan P, Roth D (2004) Sequential therapies for proliferative lupus nephritis. N Engl J Med 350:971–980PubMedCrossRef
6.
go back to reference Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, Li LS, Mysler E, Sanchez-Guerrero J, Solomons N, Wofsy D (2009) Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 20:1103–1112PubMedCrossRef Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, Li LS, Mysler E, Sanchez-Guerrero J, Solomons N, Wofsy D (2009) Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 20:1103–1112PubMedCrossRef
7.
go back to reference Ginzler EM, Wofsy D, Isenberg D, Gordon C, Lisk L, Dooley MA (2010) Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial. Arthritis Rheum 62:211–221PubMedCrossRef Ginzler EM, Wofsy D, Isenberg D, Gordon C, Lisk L, Dooley MA (2010) Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial. Arthritis Rheum 62:211–221PubMedCrossRef
8.
go back to reference Isenberg D, Appel GB, Contreras G, Dooley MA, Ginzler EM, Jayne D, Sanchez-Guerrero J, Wofsy D, Yu X, Solomons N (2010) Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatology (Oxford) 49:128–140CrossRef Isenberg D, Appel GB, Contreras G, Dooley MA, Ginzler EM, Jayne D, Sanchez-Guerrero J, Wofsy D, Yu X, Solomons N (2010) Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatology (Oxford) 49:128–140CrossRef
9.
go back to reference Radhakrishnan J, Moutzouris DA, Ginzler EM, Solomons N, Siempos II, Appel GB (2010) Mycophenolate mofetil and intravenous cyclophosphamide are similar as induction therapy for class V lupus nephritis. Kidney Int 77:152–160PubMedCrossRef Radhakrishnan J, Moutzouris DA, Ginzler EM, Solomons N, Siempos II, Appel GB (2010) Mycophenolate mofetil and intravenous cyclophosphamide are similar as induction therapy for class V lupus nephritis. Kidney Int 77:152–160PubMedCrossRef
10.
go back to reference Wofsy D, Appel GB, Dooley M, Ginzler E, Isenberg D, Jayne D, Salomon NLL, for the ALMS Study Group (2010) Aspreva lupus management study (ALMS) maintenance results. 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 24–27, Poster PO2 E23 Wofsy D, Appel GB, Dooley M, Ginzler E, Isenberg D, Jayne D, Salomon NLL, for the ALMS Study Group (2010) Aspreva lupus management study (ALMS) maintenance results. 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 24–27, Poster PO2 E23
11.
go back to reference Houssiau FA, D’Cruz D, Sangle S, Remy P, Vasconcelos C, Petrovic R, Fiehn C, de Ramon GE, Gilboe IM, Tektonidou M, Blockmans D, Ravelingien I, le Guern V, Depresseux G, Guillevin L, Cervera R (2010) Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann Rheum Dis 69:2083–2089PubMedCrossRef Houssiau FA, D’Cruz D, Sangle S, Remy P, Vasconcelos C, Petrovic R, Fiehn C, de Ramon GE, Gilboe IM, Tektonidou M, Blockmans D, Ravelingien I, le Guern V, Depresseux G, Guillevin L, Cervera R (2010) Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann Rheum Dis 69:2083–2089PubMedCrossRef
12.
go back to reference 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 38:69–78PubMedCrossRef 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 38:69–78PubMedCrossRef
13.
go back to reference Kazyra I, Pilkington C, Marks SD, Tullus K (2010) Mycophenolate mofetil treatment in children and adolescents with lupus. Arch Dis Child 95:1059–1061PubMedCrossRef Kazyra I, Pilkington C, Marks SD, Tullus K (2010) Mycophenolate mofetil treatment in children and adolescents with lupus. Arch Dis Child 95:1059–1061PubMedCrossRef
14.
go back to reference Marks SD, Tullus K (2010) Modern therapeutic strategies for paediatric systemic lupus erythematosus and lupus nephritis. Acta Paediatr 99:967–974PubMedCrossRef Marks SD, Tullus K (2010) Modern therapeutic strategies for paediatric systemic lupus erythematosus and lupus nephritis. Acta Paediatr 99:967–974PubMedCrossRef
15.
go back to reference Merrill JT, Neuwelt CM, Wallace DJ, Shanahan JC, Latinis KM, Oates JC, Utset TO, Gordon C, Isenberg DA, Hsieh HJ, Zhang D, Brunetta PG (2010) Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum 62:222–233PubMedCrossRef Merrill JT, Neuwelt CM, Wallace DJ, Shanahan JC, Latinis KM, Oates JC, Utset TO, Gordon C, Isenberg DA, Hsieh HJ, Zhang D, Brunetta PG (2010) Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum 62:222–233PubMedCrossRef
16.
go back to reference Furie R, Looney J, Rovin B, Latinis K, Appel G, Sanchez-Guerrero J, Fervenza F, Maciuca R, Zhang D, Garg J, Brunetta P, and the LUNAR study group (2010) Efficacy and safety of rituximab in patients with proliferative lupus nephritis: results from the randomized, double-blind phase III LUNAR study. 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 24–27, Poster PO2 E 6 Furie R, Looney J, Rovin B, Latinis K, Appel G, Sanchez-Guerrero J, Fervenza F, Maciuca R, Zhang D, Garg J, Brunetta P, and the LUNAR study group (2010) Efficacy and safety of rituximab in patients with proliferative lupus nephritis: results from the randomized, double-blind phase III LUNAR study. 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 24–27, Poster PO2 E 6
17.
go back to reference Furie R, Rovin B, Appel G, Kamen D, Fervenza F, Spindler A, Maciuca R, Garg J, Brunetta P, and the LUNAR study group (2010) Effect of rituximab on anti-double-stranded DNA antibody and C3 levels and relationship to response: results from the LUNAR trial. 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 24–27, Poster PO2 E 22 Furie R, Rovin B, Appel G, Kamen D, Fervenza F, Spindler A, Maciuca R, Garg J, Brunetta P, and the LUNAR study group (2010) Effect of rituximab on anti-double-stranded DNA antibody and C3 levels and relationship to response: results from the LUNAR trial. 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 24–27, Poster PO2 E 22
18.
go back to reference Mysler E, Spindler A, Guzman R, Bijl M, Jayne D, Furie R, Maciuca R, Drappa J, Shahdad S, Close D (2010) Study design and baseline patient characteristics of BELONG, the randomized double-blind, placebo-controlled phase III trial of ocrelizumab, a humanized anti-CD20 antibody, in lupus nephritis. 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 24–27, Poster PO2 E 20 Mysler E, Spindler A, Guzman R, Bijl M, Jayne D, Furie R, Maciuca R, Drappa J, Shahdad S, Close D (2010) Study design and baseline patient characteristics of BELONG, the randomized double-blind, placebo-controlled phase III trial of ocrelizumab, a humanized anti-CD20 antibody, in lupus nephritis. 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 24–27, Poster PO2 E 20
19.
go back to reference Navarra SV, Guzman RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, Li EK, Thomas M, Kim HY, Leon MG, Tanasescu C, Nasonov E, Lan JL, Pineda L, Zhong ZJ, Freimuth W, Petri MA (2011) Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 377:721–731PubMedCrossRef Navarra SV, Guzman RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, Li EK, Thomas M, Kim HY, Leon MG, Tanasescu C, Nasonov E, Lan JL, Pineda L, Zhong ZJ, Freimuth W, Petri MA (2011) Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 377:721–731PubMedCrossRef
20.
go back to reference Wallace DJ, Stohl W, Furie RA, Lisse JR, McKay JD, Merrill JT, Petri MA, Ginzler EM, Chatham WW, McCune WJ, Fernandez V, Chevrier MR, Zhong ZJ, Freimuth WW (2009) A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheum 61:1168–1178PubMedCrossRef Wallace DJ, Stohl W, Furie RA, Lisse JR, McKay JD, Merrill JT, Petri MA, Ginzler EM, Chatham WW, McCune WJ, Fernandez V, Chevrier MR, Zhong ZJ, Freimuth WW (2009) A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheum 61:1168–1178PubMedCrossRef
21.
go back to reference Petri M, Wallace D, Furie R, Merrill J, Ginzler E, Stohl W, Chatham W, McCune J, Weinstein A, Klein J, Zhong Z, Freimuth W, for the LBSL02/99 study group (2010) Five-year experience with Belimumab, a BLyS-specific inhibitor, in patients with systemic lupus erythematosus (SLE). 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 24–27, Poster PO2 E Petri M, Wallace D, Furie R, Merrill J, Ginzler E, Stohl W, Chatham W, McCune J, Weinstein A, Klein J, Zhong Z, Freimuth W, for the LBSL02/99 study group (2010) Five-year experience with Belimumab, a BLyS-specific inhibitor, in patients with systemic lupus erythematosus (SLE). 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 24–27, Poster PO2 E
22.
go back to reference Furie R (2010) Belimumab, a BlyS-specific inhibitor, reduced disease activity and severe flares in patients with seropositive SLE: BLISS-76 Study. 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 24–27 Furie R (2010) Belimumab, a BlyS-specific inhibitor, reduced disease activity and severe flares in patients with seropositive SLE: BLISS-76 Study. 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 24–27
23.
go back to reference Dorner T, Kaufmann J, Wegener WA, Teoh N, Goldenberg DM, Burmester GR (2006) Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus. Arthritis Res Ther 8:R74PubMedCrossRef Dorner T, Kaufmann J, Wegener WA, Teoh N, Goldenberg DM, Burmester GR (2006) Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus. Arthritis Res Ther 8:R74PubMedCrossRef
25.
go back to reference Pena-Rossi C, Nasonov E, Stanislav M, Yakusevich V, Ershova O, Lomareva N, Saunders H, Hill J, Nestorov I (2009) An exploratory dose-escalating study investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous atacicept in patients with systemic lupus erythematosus. Lupus 18:547–555PubMedCrossRef Pena-Rossi C, Nasonov E, Stanislav M, Yakusevich V, Ershova O, Lomareva N, Saunders H, Hill J, Nestorov I (2009) An exploratory dose-escalating study investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous atacicept in patients with systemic lupus erythematosus. Lupus 18:547–555PubMedCrossRef
26.
go back to reference Cardiel MH, Tumlin JA, Furie RA, Wallace DJ, Joh T, Linnik MD (2008) Abetimus sodium for renal flare in systemic lupus erythematosus: results of a randomized, controlled phase III trial. Arthritis Rheum 58:2470–2480PubMedCrossRef Cardiel MH, Tumlin JA, Furie RA, Wallace DJ, Joh T, Linnik MD (2008) Abetimus sodium for renal flare in systemic lupus erythematosus: results of a randomized, controlled phase III trial. Arthritis Rheum 58:2470–2480PubMedCrossRef
27.
go back to reference Aringer M, Houssiau F, Gordon C, Graninger WB, Voll RE, Rath E, Steiner G, Smolen JS (2009) Adverse events and efficacy of TNF-alpha blockade with infliximab in patients with systemic lupus erythematosus: long-term follow-up of 13 patients. Rheumatology (Oxford) 48:1451–1454CrossRef Aringer M, Houssiau F, Gordon C, Graninger WB, Voll RE, Rath E, Steiner G, Smolen JS (2009) Adverse events and efficacy of TNF-alpha blockade with infliximab in patients with systemic lupus erythematosus: long-term follow-up of 13 patients. Rheumatology (Oxford) 48:1451–1454CrossRef
28.
go back to reference Illei GG, Shirota Y, Yarboro CH, Daruwalla J, Tackey E, Takada K, Fleisher T, Balow JE, Lipsky PE (2010) Tocilizumab in systemic lupus erythematosus: data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum 62:542–552PubMedCrossRef Illei GG, Shirota Y, Yarboro CH, Daruwalla J, Tackey E, Takada K, Fleisher T, Balow JE, Lipsky PE (2010) Tocilizumab in systemic lupus erythematosus: data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum 62:542–552PubMedCrossRef
29.
go back to reference Merrill JT, Burgos-Vargas R, Westhovens R, Chalmers A, D’Cruz D, Wallace DJ, Bae SC, Sigal L, Becker JC, Kelly S, Raghupathi K, Li T, Peng Y, Kinaszczuk M, Nash P (2010) The efficacy and safety of abatacept in patients with non-life-threatening manifestations of systemic lupus erythematosus: results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 62:3077–3087PubMedCrossRef Merrill JT, Burgos-Vargas R, Westhovens R, Chalmers A, D’Cruz D, Wallace DJ, Bae SC, Sigal L, Becker JC, Kelly S, Raghupathi K, Li T, Peng Y, Kinaszczuk M, Nash P (2010) The efficacy and safety of abatacept in patients with non-life-threatening manifestations of systemic lupus erythematosus: results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 62:3077–3087PubMedCrossRef
30.
go back to reference D’Andrea D, Xie F, Zimmer R (2010) A randomized, double-blind, placebo-controlled study of spliceosomal peptide rigerimod in patients with systemic lupus erythematosus (SLE). 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 24–27, Poster PO2 E D’Andrea D, Xie F, Zimmer R (2010) A randomized, double-blind, placebo-controlled study of spliceosomal peptide rigerimod in patients with systemic lupus erythematosus (SLE). 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 24–27, Poster PO2 E
Metadata
Title
New developments in the treatment of systemic lupus erythematosus
Author
Kjell Tullus
Publication date
01-05-2012
Publisher
Springer-Verlag
Published in
Pediatric Nephrology / Issue 5/2012
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-011-1859-0

Other articles of this Issue 5/2012

Pediatric Nephrology 5/2012 Go to the issue