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Erschienen in: Clinical Rheumatology 4/2014

01.04.2014 | Review Article

Systemic lupus erythematosus: a therapeutic challenge for the XXI century

verfasst von: Manuel F. Ugarte-Gil, Graciela S Alarcón

Erschienen in: Clinical Rheumatology | Ausgabe 4/2014

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Abstract

Despite significant advances in our understanding of the pathogenesis of systemic lupus erythematosus (SLE), there are only a few drugs approved by the regulatory agencies across the world for the treatment of these patients; in fact, many of the compounds subjected to clinical trials have failed in achieving their primary endpoints. Current therapeutic options include antimalarials which should be used in all SLE patients unless they are strongly contraindicated, glucocorticoids which should be used at the lowest possible dose and for the shortest possible time, and immunosuppressive drugs which should be used judiciously, mainly in patients with severe organ involvements or receiving high doses of steroids to control their disease. Despite improvement on the survival of SLE patients, damage accrual has not varied over the last few decades, reflecting a gap between these therapeutic options and the expectations of these patients and their treating physicians. Biologic compounds can be used in some refractory cases. However, their cost is of great concern for both the patients and the health system. Cost is of special importance in low-income countries, because low-income SLE patients tend to experience a more severe disease having an overall worse prognosis which is compounded by their limited access to the health system. Although a treatment to target based on defined molecular pathways for specific disease subsets is appealing, this is not yet a reality. This review addressed current therapeutic options for SLE patients and the state of the art of investigational drugs targeting pathogenic pathways identified in these patients.
Literatur
1.
Zurück zum Zitat Borchers AT, Keen CL, Shoenfeld Y, Gershwin ME (2004) Surviving the butterfly and the wolf: mortality trends in systemic lupus erythematosus. Autoimmun Rev 3(6):423–453PubMedCrossRef Borchers AT, Keen CL, Shoenfeld Y, Gershwin ME (2004) Surviving the butterfly and the wolf: mortality trends in systemic lupus erythematosus. Autoimmun Rev 3(6):423–453PubMedCrossRef
2.
Zurück zum Zitat Kasitanon N, Magder LS, Petri M (2006) Predictors of survival in systemic lupus erythematosus. Medicine (Baltimore) 85(3):147–156CrossRef Kasitanon N, Magder LS, Petri M (2006) Predictors of survival in systemic lupus erythematosus. Medicine (Baltimore) 85(3):147–156CrossRef
3.
Zurück zum Zitat Alarcon GS, Bastian HM, Beasley TM, Roseman JM, Tan FK, Fessler BJ, Vila LM, McGwin G Jr (2006) Systemic lupus erythematosus in a multi-ethnic cohort (LUMINA) XXXII: [corrected] contributions of admixture and socioeconomic status to renal involvement. Lupus 15(1):26–31PubMedCrossRef Alarcon GS, Bastian HM, Beasley TM, Roseman JM, Tan FK, Fessler BJ, Vila LM, McGwin G Jr (2006) Systemic lupus erythematosus in a multi-ethnic cohort (LUMINA) XXXII: [corrected] contributions of admixture and socioeconomic status to renal involvement. Lupus 15(1):26–31PubMedCrossRef
4.
Zurück zum Zitat Alarcon GS, Roseman J, Bartolucci AA, Friedman AW, Moulds JM, Goel N, Straaton KV, Reveille JD (1998) Systemic lupus erythematosus in three ethnic groups: II. Features predictive of disease activity early in its course. LUMINA Study Group. Lupus in minority populations, nature versus nurture. Arthritis Rheum 41(7):1173–1180PubMedCrossRef Alarcon GS, Roseman J, Bartolucci AA, Friedman AW, Moulds JM, Goel N, Straaton KV, Reveille JD (1998) Systemic lupus erythematosus in three ethnic groups: II. Features predictive of disease activity early in its course. LUMINA Study Group. Lupus in minority populations, nature versus nurture. Arthritis Rheum 41(7):1173–1180PubMedCrossRef
5.
Zurück zum Zitat Duran S, Apte M, Alarcon GS (2007) Poverty, not ethnicity, accounts for the differential mortality rates among lupus patients of various ethnic groups. J Natl Med Assoc 99(10):1196–1198PubMedCentralPubMed Duran S, Apte M, Alarcon GS (2007) Poverty, not ethnicity, accounts for the differential mortality rates among lupus patients of various ethnic groups. J Natl Med Assoc 99(10):1196–1198PubMedCentralPubMed
6.
Zurück zum Zitat Sanchez ML, McGwin G Jr, Duran S, Fernandez M, Reveille JD, Vila LM, Alarcon GS (2009) Factors predictive of overall health over the course of the disease in patients with systemic lupus erythematosus from the LUMINA cohort (LXII): use of the SF-6D. Clin Exp Rheumatol 27(1):67–71PubMed Sanchez ML, McGwin G Jr, Duran S, Fernandez M, Reveille JD, Vila LM, Alarcon GS (2009) Factors predictive of overall health over the course of the disease in patients with systemic lupus erythematosus from the LUMINA cohort (LXII): use of the SF-6D. Clin Exp Rheumatol 27(1):67–71PubMed
7.
Zurück zum Zitat 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(5):1103–1112PubMedCentralPubMedCrossRef 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(5):1103–1112PubMedCentralPubMedCrossRef
8.
Zurück zum Zitat Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA (2010) Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 69(1):20–28PubMedCrossRef Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA (2010) Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 69(1):20–28PubMedCrossRef
9.
Zurück zum Zitat Ruiz-Irastorza G, Danza A, Khamashta M (2012) Glucocorticoid use and abuse in SLE. Rheumatology (Oxford) 51(7):1145–1153CrossRef Ruiz-Irastorza G, Danza A, Khamashta M (2012) Glucocorticoid use and abuse in SLE. Rheumatology (Oxford) 51(7):1145–1153CrossRef
10.
Zurück zum Zitat Barile-Fabris L, Ariza-Andraca R, Olguin-Ortega L, Jara LJ, Fraga-Mouret A, Miranda-Limon JM, Fuentes de la Mata J, Clark P, Vargas F, Alocer-Varela J (2005) Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus. Ann Rheum Dis 64(4):620–625PubMedCentralPubMedCrossRef Barile-Fabris L, Ariza-Andraca R, Olguin-Ortega L, Jara LJ, Fraga-Mouret A, Miranda-Limon JM, Fuentes de la Mata J, Clark P, Vargas F, Alocer-Varela J (2005) Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus. Ann Rheum Dis 64(4):620–625PubMedCentralPubMedCrossRef
11.
Zurück zum Zitat Petri M (2004) Cyclophosphamide: new approaches for systemic lupus erythematosus. Lupus 13(5):366–371PubMedCrossRef Petri M (2004) Cyclophosphamide: new approaches for systemic lupus erythematosus. Lupus 13(5):366–371PubMedCrossRef
12.
Zurück zum Zitat Gourley MF, Austin HA 3rd, Scott D, Yarboro CH, Vaughan EM, Muir J, Boumpas DT, Klippel JH, Balow JE, Steinberg AD (1996) Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med 125(7):549–557PubMedCrossRef Gourley MF, Austin HA 3rd, Scott D, Yarboro CH, Vaughan EM, Muir J, Boumpas DT, Klippel JH, Balow JE, Steinberg AD (1996) Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med 125(7):549–557PubMedCrossRef
13.
Zurück zum Zitat Yildirim-Toruner C, Diamond B (2011) Current and novel therapeutics in the treatment of systemic lupus erythematosus. J Allergy Clin Immunol 127(2):303–312PubMedCentralPubMedCrossRef Yildirim-Toruner C, Diamond B (2011) Current and novel therapeutics in the treatment of systemic lupus erythematosus. J Allergy Clin Immunol 127(2):303–312PubMedCentralPubMedCrossRef
14.
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(1):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(1):69–78PubMedCrossRef
15.
Zurück zum Zitat 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(1):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(1):128–140CrossRef
16.
Zurück zum Zitat Dooley MA, Jayne D, Ginzler EM, Isenberg D, Olsen NJ, Wofsy D, Eitner F, Appel GB, Contreras G, Lisk L, Solomons N (2011) Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med 365(20):1886–1895PubMedCrossRef Dooley MA, Jayne D, Ginzler EM, Isenberg D, Olsen NJ, Wofsy D, Eitner F, Appel GB, Contreras G, Lisk L, Solomons N (2011) Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med 365(20):1886–1895PubMedCrossRef
17.
Zurück zum Zitat Ginzler E, Sharon E, Diamond H, Kaplan D (1975) Long-term maintenance therapy with azathioprine in systemic lupus erythematosus. Arthritis Rheum 18(1):27–34PubMedCrossRef Ginzler E, Sharon E, Diamond H, Kaplan D (1975) Long-term maintenance therapy with azathioprine in systemic lupus erythematosus. Arthritis Rheum 18(1):27–34PubMedCrossRef
18.
Zurück zum Zitat 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(10):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(10):971–980PubMedCrossRef
19.
Zurück zum Zitat Fortin PR, Abrahamowicz M, Ferland D, Lacaille D, Smith CD, Zummer M (2008) Steroid-sparing effects of methotrexate in systemic lupus erythematosus: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 59(12):1796–1804PubMedCrossRef Fortin PR, Abrahamowicz M, Ferland D, Lacaille D, Smith CD, Zummer M (2008) Steroid-sparing effects of methotrexate in systemic lupus erythematosus: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 59(12):1796–1804PubMedCrossRef
20.
Zurück zum Zitat Carneiro JR, Sato EI (1999) Double blind, randomized, placebo controlled clinical trial of methotrexate in systemic lupus erythematosus. J Rheumatol 26(6):1275–1279PubMed Carneiro JR, Sato EI (1999) Double blind, randomized, placebo controlled clinical trial of methotrexate in systemic lupus erythematosus. J Rheumatol 26(6):1275–1279PubMed
21.
Zurück zum Zitat Moroni G, Doria A, Ponticelli C (2009) Cyclosporine (CsA) in lupus nephritis: assessing the evidence. Nephrol Dial Transplant 24(1):15–20PubMedCrossRef Moroni G, Doria A, Ponticelli C (2009) Cyclosporine (CsA) in lupus nephritis: assessing the evidence. Nephrol Dial Transplant 24(1):15–20PubMedCrossRef
22.
Zurück zum Zitat Ogawa H, Kameda H, Amano K, Takeuchi T (2010) Efficacy and safety of cyclosporine A in patients with refractory systemic lupus erythematosus in a daily clinical practice. Lupus 19(2):162–169PubMedCrossRef Ogawa H, Kameda H, Amano K, Takeuchi T (2010) Efficacy and safety of cyclosporine A in patients with refractory systemic lupus erythematosus in a daily clinical practice. Lupus 19(2):162–169PubMedCrossRef
23.
Zurück zum Zitat Deng J, Huo D, Wu Q, Yang Z, Liao Y (2012) A meta-analysis of randomized controlled trials comparing tacrolimus with intravenous cyclophosphamide in the induction treatment for lupus nephritis. Tohoku J Exp Med 227(4):281–288PubMedCrossRef Deng J, Huo D, Wu Q, Yang Z, Liao Y (2012) A meta-analysis of randomized controlled trials comparing tacrolimus with intravenous cyclophosphamide in the induction treatment for lupus nephritis. Tohoku J Exp Med 227(4):281–288PubMedCrossRef
24.
Zurück zum Zitat Chen W, Liu Q, Tang X, Fu P, Liu F, Liao Y, Yang Z, Zhang J, Chen J, Lou T, Fu J, Kong Y, Liu Z, Li Z, Yu X (2012) Outcomes of maintenance therapy with tacrolimus versus azathioprine for active lupus nephritis: a multicenter randomized clinical trial. Lupus 21(9):944–952PubMedCrossRef Chen W, Liu Q, Tang X, Fu P, Liu F, Liao Y, Yang Z, Zhang J, Chen J, Lou T, Fu J, Kong Y, Liu Z, Li Z, Yu X (2012) Outcomes of maintenance therapy with tacrolimus versus azathioprine for active lupus nephritis: a multicenter randomized clinical trial. Lupus 21(9):944–952PubMedCrossRef
25.
Zurück zum Zitat Lanata CM, Mahmood T, Fine DM, Petri M (2010) Combination therapy of mycophenolate mofetil and tacrolimus in lupus nephritis. Lupus 19(8):935–940PubMedCrossRef Lanata CM, Mahmood T, Fine DM, Petri M (2010) Combination therapy of mycophenolate mofetil and tacrolimus in lupus nephritis. Lupus 19(8):935–940PubMedCrossRef
26.
Zurück zum Zitat Tam LS, Li EK, Wong CK, Lam CW, Szeto CC (2004) Double-blind, randomized, placebo-controlled pilot study of leflunomide in systemic lupus erythematosus. Lupus 13(8):601–604PubMedCrossRef Tam LS, Li EK, Wong CK, Lam CW, Szeto CC (2004) Double-blind, randomized, placebo-controlled pilot study of leflunomide in systemic lupus erythematosus. Lupus 13(8):601–604PubMedCrossRef
27.
Zurück zum Zitat Wang HY, Cui TG, Hou FF, Ni ZH, Chen XM, Lu FM, Xu FF, Yu XQ, Zhang FS, Zhao XZ, Zhao MH, Wang GB, Qian JQ, Cai GY, Zhu TY, Wang YH, Jiang ZP, Li YN, Mei CL, Zou WZ (2008) Induction treatment of proliferative lupus nephritis with leflunomide combined with prednisone: a prospective multi-centre observational study. Lupus 17(7):638–644PubMedCrossRef Wang HY, Cui TG, Hou FF, Ni ZH, Chen XM, Lu FM, Xu FF, Yu XQ, Zhang FS, Zhao XZ, Zhao MH, Wang GB, Qian JQ, Cai GY, Zhu TY, Wang YH, Jiang ZP, Li YN, Mei CL, Zou WZ (2008) Induction treatment of proliferative lupus nephritis with leflunomide combined with prednisone: a prospective multi-centre observational study. Lupus 17(7):638–644PubMedCrossRef
28.
Zurück zum Zitat Wu GC, Xu XD, Huang Q, Wu H (2013) Leflunomide: friend or foe for systemic lupus erythematosus? Rheumatol Int 33(2):273–276PubMedCrossRef Wu GC, Xu XD, Huang Q, Wu H (2013) Leflunomide: friend or foe for systemic lupus erythematosus? Rheumatol Int 33(2):273–276PubMedCrossRef
29.
Zurück zum Zitat Yurkovich M, Vostretsova K, Chen W, Avina-Zubieta JA (2013) Overall and cause-specific mortality in patients with systemic lupus erythematosus: a meta-analysis of observational studies. Arthritis Care Res. doi:10.1002/acr.22173 Yurkovich M, Vostretsova K, Chen W, Avina-Zubieta JA (2013) Overall and cause-specific mortality in patients with systemic lupus erythematosus: a meta-analysis of observational studies. Arthritis Care Res. doi:10.​1002/​acr.​22173
30.
Zurück zum Zitat Urowitz MB, Gladman DD, Tom BD, Ibanez D, Farewell VT (2008) Changing patterns in mortality and disease outcomes for patients with systemic lupus erythematosus. J Rheumatol 35(11):2152–2158PubMedCrossRef Urowitz MB, Gladman DD, Tom BD, Ibanez D, Farewell VT (2008) Changing patterns in mortality and disease outcomes for patients with systemic lupus erythematosus. J Rheumatol 35(11):2152–2158PubMedCrossRef
31.
Zurück zum Zitat Manzi S, Sanchez-Guerrero J, Merrill JT, Furie R, Gladman D, Navarra SV, Ginzler EM, D’Cruz DP, Doria A, Cooper S, Zhong ZJ, Hough D, Freimuth W, Petri MA (2012) Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials. Ann Rheum Dis 71(11):1833–1838PubMedCentralPubMedCrossRef Manzi S, Sanchez-Guerrero J, Merrill JT, Furie R, Gladman D, Navarra SV, Ginzler EM, D’Cruz DP, Doria A, Cooper S, Zhong ZJ, Hough D, Freimuth W, Petri MA (2012) Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials. Ann Rheum Dis 71(11):1833–1838PubMedCentralPubMedCrossRef
32.
Zurück zum Zitat Terrier B, Amoura Z, Ravaud P, Hachulla E, Jouenne R, Combe B, Bonnet C, Cacoub P, Cantagrel A, de Bandt M, Fain O, Fautrel B, Gaudin P, Godeau B, Harle JR, Hot A, Kahn JE, Lambotte O, Larroche C, Leone J, Meyer O, Pallot-Prades B, Pertuiset E, Quartier P, Schaerverbeke T, Sibilia J, Somogyi A, Soubrier M, Vignon E, Bader-Meunier B, Mariette X, Gottenberg JE (2010) Safety and efficacy of rituximab in systemic lupus erythematosus: results from 136 patients from the French autoimmunity and rituximab registry. Arthritis Rheum 62(8):2458–2466PubMedCrossRef Terrier B, Amoura Z, Ravaud P, Hachulla E, Jouenne R, Combe B, Bonnet C, Cacoub P, Cantagrel A, de Bandt M, Fain O, Fautrel B, Gaudin P, Godeau B, Harle JR, Hot A, Kahn JE, Lambotte O, Larroche C, Leone J, Meyer O, Pallot-Prades B, Pertuiset E, Quartier P, Schaerverbeke T, Sibilia J, Somogyi A, Soubrier M, Vignon E, Bader-Meunier B, Mariette X, Gottenberg JE (2010) Safety and efficacy of rituximab in systemic lupus erythematosus: results from 136 patients from the French autoimmunity and rituximab registry. Arthritis Rheum 62(8):2458–2466PubMedCrossRef
33.
Zurück zum Zitat Narvaez J, Rios–Rodriguez V, de la Fuente D, Estrada P, Lopez-Vives L, Gomez-Vaquero C, Nolla JM (2011) Rituximab therapy in refractory neuropsychiatric lupus: current clinical evidence. Semin Arthritis Rheum 41(3):364PubMedCrossRef Narvaez J, Rios–Rodriguez V, de la Fuente D, Estrada P, Lopez-Vives L, Gomez-Vaquero C, Nolla JM (2011) Rituximab therapy in refractory neuropsychiatric lupus: current clinical evidence. Semin Arthritis Rheum 41(3):364PubMedCrossRef
34.
Zurück zum Zitat Diaz-Lagares C, Croca S, Sangle S, Vital EM, Catapano F, Martinez-Berriotxoa A, Garcia-Hernandez F, Callejas-Rubio JL, Rascon J, D’Cruz D, Jayne D, Ruiz-Irastorza G, Emery P, Isenberg D, Ramos-Casals M, Khamashta MA (2012) Efficacy of rituximab in 164 patients with biopsy-proven lupus nephritis: pooled data from European cohorts. Autoimmun Rev 11(5):357–364PubMedCrossRef Diaz-Lagares C, Croca S, Sangle S, Vital EM, Catapano F, Martinez-Berriotxoa A, Garcia-Hernandez F, Callejas-Rubio JL, Rascon J, D’Cruz D, Jayne D, Ruiz-Irastorza G, Emery P, Isenberg D, Ramos-Casals M, Khamashta MA (2012) Efficacy of rituximab in 164 patients with biopsy-proven lupus nephritis: pooled data from European cohorts. Autoimmun Rev 11(5):357–364PubMedCrossRef
35.
Zurück zum Zitat Dall’Era M, Wofsy D (2009) Systemic lupus erythematosus clinical trials—an interim analysis. Nat Rev Rheumatol 5(6):348–351PubMedCrossRef Dall’Era M, Wofsy D (2009) Systemic lupus erythematosus clinical trials—an interim analysis. Nat Rev Rheumatol 5(6):348–351PubMedCrossRef
36.
Zurück zum Zitat 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(10):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(10):3077–3087PubMedCrossRef
37.
Zurück zum Zitat Wofsy D, Hillson JL, Diamond B (2012) Abatacept for lupus nephritis: alternative definitions of complete response support conflicting conclusions. Arthritis Rheum 64(11):3660–3665PubMedCrossRef Wofsy D, Hillson JL, Diamond B (2012) Abatacept for lupus nephritis: alternative definitions of complete response support conflicting conclusions. Arthritis Rheum 64(11):3660–3665PubMedCrossRef
38.
Zurück zum Zitat Condon MB, Ashby D, Pepper RJ, Cook HT, Levy JB, Griffith M, Cairns TD, Lightstone L (2013) 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 72(8):1280–1286PubMedCrossRef Condon MB, Ashby D, Pepper RJ, Cook HT, Levy JB, Griffith M, Cairns TD, Lightstone L (2013) 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 72(8):1280–1286PubMedCrossRef
39.
Zurück zum Zitat Petri M, Wallace DJ, Spindler A, Chindalore V, Kalunian K, Mysler E, Neuwelt CM, Robbie G, White WI, Higgs BW, Yao Y, Wang L, Ethgen D, Greth W (2013) Sifalimumab, a human anti-interferon-alpha monoclonal antibody, in systemic lupus erythematosus: a phase I randomized, controlled, dose-escalation study. Arthritis Rheum 65(4):1011–1021PubMedCentralPubMedCrossRef Petri M, Wallace DJ, Spindler A, Chindalore V, Kalunian K, Mysler E, Neuwelt CM, Robbie G, White WI, Higgs BW, Yao Y, Wang L, Ethgen D, Greth W (2013) Sifalimumab, a human anti-interferon-alpha monoclonal antibody, in systemic lupus erythematosus: a phase I randomized, controlled, dose-escalation study. Arthritis Rheum 65(4):1011–1021PubMedCentralPubMedCrossRef
40.
Zurück zum Zitat Merrill JT, Maciuca R, Ouyang W, McBride JM, Townsend MJ, Park E, Li J, Wei X, Morimoto A, Boismenu R, Davis JC Jr, Kennedy WP (2012) Efficacy and safety of rontalizumab (anti-interferon alpha) in SLE subjects with restricted immunosuppressant use: results of a randomized, double-blind, placebo-controlled phase 2 study. Arthritis Rheum 64(10):S1111, supplCrossRef Merrill JT, Maciuca R, Ouyang W, McBride JM, Townsend MJ, Park E, Li J, Wei X, Morimoto A, Boismenu R, Davis JC Jr, Kennedy WP (2012) Efficacy and safety of rontalizumab (anti-interferon alpha) in SLE subjects with restricted immunosuppressant use: results of a randomized, double-blind, placebo-controlled phase 2 study. Arthritis Rheum 64(10):S1111, supplCrossRef
41.
Zurück zum Zitat Tcherepanova I, Curtis M, Sale M, Miesowicz F, Nicolette C (2012) Results of a randomized placebo controlled phase Ia study of AGS-009, a humanized anti-interferon-α monoclonal antibody in subjects with systemic lupus erythematosus. Ann Rheum Dis 71(Suppl 3):356 Tcherepanova I, Curtis M, Sale M, Miesowicz F, Nicolette C (2012) Results of a randomized placebo controlled phase Ia study of AGS-009, a humanized anti-interferon-α monoclonal antibody in subjects with systemic lupus erythematosus. Ann Rheum Dis 71(Suppl 3):356
43.
Zurück zum Zitat Lauwerys BR, Hachulla E, Spertini F, Lazaro E, Jorgensen C, Mariette X, Haelterman E, Grouard-Vogel G, Fanget B, Dhellin O, Vandepapeliere P, Houssiau FA (2013) Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon alpha-kinoid. Arthritis Rheum 65(2):447–456PubMedCrossRef Lauwerys BR, Hachulla E, Spertini F, Lazaro E, Jorgensen C, Mariette X, Haelterman E, Grouard-Vogel G, Fanget B, Dhellin O, Vandepapeliere P, Houssiau FA (2013) Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon alpha-kinoid. Arthritis Rheum 65(2):447–456PubMedCrossRef
45.
Zurück zum Zitat Medical University of V, Hospital H, Medical University of G, Charite University BG, University of E-N, Heinrich-Heine University D, University Medical Centre G, Leiden University Medical C, Radboud U (2009) TNF blockade with remicade in active lupus nephritis WHO class V (TRIAL ). http://ClinicalTrials.gov/show/NCT00368264. Accessed 04 February 2014 Medical University of V, Hospital H, Medical University of G, Charite University BG, University of E-N, Heinrich-Heine University D, University Medical Centre G, Leiden University Medical C, Radboud U (2009) TNF blockade with remicade in active lupus nephritis WHO class V (TRIAL ). http://​ClinicalTrials.​gov/​show/​NCT00368264. Accessed 04 February 2014
51.
Zurück zum Zitat De Souza A, Strober BE, Merola JF, Oliver S, Franks AG Jr (2012) Apremilast for discoid lupus erythematosus: results of a phase 2, open-label, single-arm, pilot study. J Drugs Dermatol 11(10):1224–1226PubMed De Souza A, Strober BE, Merola JF, Oliver S, Franks AG Jr (2012) Apremilast for discoid lupus erythematosus: results of a phase 2, open-label, single-arm, pilot study. J Drugs Dermatol 11(10):1224–1226PubMed
52.
Zurück zum Zitat Invion I (2014) Double-blinded, randomized, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics, and biochemical activity of intravenous Cpn10 administration in subjects with SLE. http://ClinicalTrials.gov/show/NCT01838694. Accessed 04 February 2014 Invion I (2014) Double-blinded, randomized, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics, and biochemical activity of intravenous Cpn10 administration in subjects with SLE. http://​ClinicalTrials.​gov/​show/​NCT01838694. Accessed 04 February 2014
53.
Zurück zum Zitat Mysler EF, Spindler AJ, Guzman R, Bijl M, Jayne D, Furie RA, Houssiau FA, Drappa J, Close D, Maciuca R, Rao K, Shahdad S, Brunetta P (2013) Efficacy and safety of ocrelizumab in active proliferative lupus nephritis: results from a randomized, double-blind, phase III study. Arthritis Rheum 65(9):2368–2379PubMedCrossRef Mysler EF, Spindler AJ, Guzman R, Bijl M, Jayne D, Furie RA, Houssiau FA, Drappa J, Close D, Maciuca R, Rao K, Shahdad S, Brunetta P (2013) Efficacy and safety of ocrelizumab in active proliferative lupus nephritis: results from a randomized, double-blind, phase III study. Arthritis Rheum 65(9):2368–2379PubMedCrossRef
55.
Zurück zum Zitat Fleischmann R, Cohen S, Pardo P, Shaw M, Bhattacharya I, Sridharan S, Diehl A, Gourley I (2010) B cell depletion in subjects with controlled systemic lupus erythematosus (SLE) after intravenous or subcutaneous administration of SBI-087. Ann Rheum Dis 69(Suppl 3):550 Fleischmann R, Cohen S, Pardo P, Shaw M, Bhattacharya I, Sridharan S, Diehl A, Gourley I (2010) B cell depletion in subjects with controlled systemic lupus erythematosus (SLE) after intravenous or subcutaneous administration of SBI-087. Ann Rheum Dis 69(Suppl 3):550
56.
Zurück zum Zitat Wallace DJ, Kalunian K, Petri MA, Strand V, Houssiau FA, Pike M, Kilgallen B, Bongardt S, Barry A, Kelley L, Gordon C (2014) Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study. Ann Rheum Dis 73(1):183–190PubMedCentralPubMedCrossRef Wallace DJ, Kalunian K, Petri MA, Strand V, Houssiau FA, Pike M, Kilgallen B, Bongardt S, Barry A, Kelley L, Gordon C (2014) Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study. Ann Rheum Dis 73(1):183–190PubMedCentralPubMedCrossRef
57.
Zurück zum Zitat Wallace DJ, Gordon C, Strand V, Hobbs K, Petri M, Kalunian K, Houssiau F, Tak PP, Isenberg DA, Kelley L, Kilgallen B, Barry AN, Wegener WA, Goldenberg DM (2013) Efficacy and safety of epratuzumab in patients with moderate/severe flaring systemic lupus erythematosus: results from two randomized, double-blind, placebo-controlled, multicentre studies (ALLEVIATE) and follow-up. Rheumatology (Oxford) 52(7):1313–1322CrossRef Wallace DJ, Gordon C, Strand V, Hobbs K, Petri M, Kalunian K, Houssiau F, Tak PP, Isenberg DA, Kelley L, Kilgallen B, Barry AN, Wegener WA, Goldenberg DM (2013) Efficacy and safety of epratuzumab in patients with moderate/severe flaring systemic lupus erythematosus: results from two randomized, double-blind, placebo-controlled, multicentre studies (ALLEVIATE) and follow-up. Rheumatology (Oxford) 52(7):1313–1322CrossRef
59.
Zurück zum Zitat Furie R, Scheinberg M, Leon G, Ramiterre EB, Thomas M, Chu AD, Hislop C, Martin RS, Petri MA (2013) Effects of blisibimod, an inhibitor of B-cell activating factor, on markers of renal disease in patients with SLE. Ann Rheum Dis 72(Suppl 3):95 Furie R, Scheinberg M, Leon G, Ramiterre EB, Thomas M, Chu AD, Hislop C, Martin RS, Petri MA (2013) Effects of blisibimod, an inhibitor of B-cell activating factor, on markers of renal disease in patients with SLE. Ann Rheum Dis 72(Suppl 3):95
60.
Zurück zum Zitat Ginzler EM, Wax S, Rajeswaran A, Copt S, Hillson J, Ramos E, Singer NG (2012) Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. Arthritis Res Ther 14(1):R33PubMedCentralPubMedCrossRef Ginzler EM, Wax S, Rajeswaran A, Copt S, Hillson J, Ramos E, Singer NG (2012) Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. Arthritis Res Ther 14(1):R33PubMedCentralPubMedCrossRef
62.
Zurück zum Zitat de Wilt LH, Kroon J, Jansen G, de Jong S, Peters GJ, Kruyt FA (2013) Bortezomib and TRAIL: a perfect match for apoptotic elimination of tumour cells? Crit Rev Oncol Hematol 85(3):363–372PubMedCrossRef de Wilt LH, Kroon J, Jansen G, de Jong S, Peters GJ, Kruyt FA (2013) Bortezomib and TRAIL: a perfect match for apoptotic elimination of tumour cells? Crit Rev Oncol Hematol 85(3):363–372PubMedCrossRef
64.
Zurück zum Zitat 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(8):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(8):2470–2480PubMedCrossRef
67.
Zurück zum Zitat Kalunian KC, Davis JC Jr, Merrill JT, Totoritis MC, Wofsy D (2002) Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 46(12):3251–3258PubMedCrossRef Kalunian KC, Davis JC Jr, Merrill JT, Totoritis MC, Wofsy D (2002) Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 46(12):3251–3258PubMedCrossRef
68.
Zurück zum Zitat Boumpas DT, Furie R, Manzi S, Illei GG, Wallace DJ, Balow JE, Vaishnaw A (2003) A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis. Arthritis Rheum 48(3):719–727PubMedCrossRef Boumpas DT, Furie R, Manzi S, Illei GG, Wallace DJ, Balow JE, Vaishnaw A (2003) A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis. Arthritis Rheum 48(3):719–727PubMedCrossRef
75.
Zurück zum Zitat Szepietowski JC, Nilganuwong S, Wozniacka A, Kuhn A, Nyberg F, van Vollenhoven RF, Bengtsson AA, Reich A, de Vries DE, van Hartingsveldt B, Robinson DW Jr, Gordon R, Hsu B (2013) Phase I, randomized, double-blind, placebo-controlled, multiple intravenous, dose-ascending study of sirukumab in cutaneous or systemic lupus erythematosus. Arthritis Rheum 65(10):2661–2671PubMed Szepietowski JC, Nilganuwong S, Wozniacka A, Kuhn A, Nyberg F, van Vollenhoven RF, Bengtsson AA, Reich A, de Vries DE, van Hartingsveldt B, Robinson DW Jr, Gordon R, Hsu B (2013) Phase I, randomized, double-blind, placebo-controlled, multiple intravenous, dose-ascending study of sirukumab in cutaneous or systemic lupus erythematosus. Arthritis Rheum 65(10):2661–2671PubMed
79.
Zurück zum Zitat Werth VP, Fiorentino D, Cohen SB, Fivenson D, Hansen C, Zoog S, Arnold G, Wang C, Boedigheimer M, Welcher A, Chung J, Sullivan B, Martin DA (2013) Phase I single-dose crossover study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical efficacy of AMG 811 (anti-IFN-gamma) in subjects with discoid lupus erythematosus. Arthritis Rheum 65 (10 (suppl)):S682 Werth VP, Fiorentino D, Cohen SB, Fivenson D, Hansen C, Zoog S, Arnold G, Wang C, Boedigheimer M, Welcher A, Chung J, Sullivan B, Martin DA (2013) Phase I single-dose crossover study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical efficacy of AMG 811 (anti-IFN-gamma) in subjects with discoid lupus erythematosus. Arthritis Rheum 65 (10 (suppl)):S682
80.
Zurück zum Zitat Llorente L, Richaud-Patin Y, Garcia-Padilla C, Claret E, Jakez-Ocampo J, Cardiel MH, Alcocer-Varela J, Grangeot-Keros L, Alarcon-Segovia D, Wijdenes J, Galanaud P, Emilie D (2000) Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus. Arthritis Rheum 43(8):1790–1800PubMedCrossRef Llorente L, Richaud-Patin Y, Garcia-Padilla C, Claret E, Jakez-Ocampo J, Cardiel MH, Alcocer-Varela J, Grangeot-Keros L, Alarcon-Segovia D, Wijdenes J, Galanaud P, Emilie D (2000) Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus. Arthritis Rheum 43(8):1790–1800PubMedCrossRef
85.
Zurück zum Zitat Jayne D, Appel G, Chan T, Barkay H, Weiss R, Wofsy D (2013) A randomized controlled study of laquinimod in active lupus nephritis patients in combination with standard of care. Ann Rheum Dis 72(suppl 3):164 Jayne D, Appel G, Chan T, Barkay H, Weiss R, Wofsy D (2013) A randomized controlled study of laquinimod in active lupus nephritis patients in combination with standard of care. Ann Rheum Dis 72(suppl 3):164
86.
Zurück zum Zitat Bengtsson A, Sturfelt G, Rönnblon L, Gunnarsson L, Svenungsson E, Jacobsen S, Lood C, Sparre B, Wallén Öhman M, Tuvesson H, Leanderson T (2011) An exploratory study to evaluate changes in disease activity and biomarkers during treatment with ABR-215757 in patients with mild active systemic lupus erythematosus (SLE). Ann Rheum Dis 70(Suppl 3):316 Bengtsson A, Sturfelt G, Rönnblon L, Gunnarsson L, Svenungsson E, Jacobsen S, Lood C, Sparre B, Wallén Öhman M, Tuvesson H, Leanderson T (2011) An exploratory study to evaluate changes in disease activity and biomarkers during treatment with ABR-215757 in patients with mild active systemic lupus erythematosus (SLE). Ann Rheum Dis 70(Suppl 3):316
88.
Zurück zum Zitat Sun Y, Wang W, Shan B, Di J, Chen L, Ren L, Li W, Li DJ, Lin Y (2011) FTY720-induced conversion of conventional Foxp3–CD4+ T cells to Foxp3+ regulatory T cells in NOD mice. Am J Reprod Immunol 66(5):349–362PubMedCrossRef Sun Y, Wang W, Shan B, Di J, Chen L, Ren L, Li W, Li DJ, Lin Y (2011) FTY720-induced conversion of conventional Foxp3–CD4+ T cells to Foxp3+ regulatory T cells in NOD mice. Am J Reprod Immunol 66(5):349–362PubMedCrossRef
90.
Zurück zum Zitat Monneaux F, Hoebeke J, Sordet C, Nonn C, Briand JP, Maillere B, Sibillia J, Muller S (2005) Selective modulation of CD4+ T cells from lupus patients by a promiscuous, protective peptide analog. J Immunol 175(9):5839–5847PubMedCrossRef Monneaux F, Hoebeke J, Sordet C, Nonn C, Briand JP, Maillere B, Sibillia J, Muller S (2005) Selective modulation of CD4+ T cells from lupus patients by a promiscuous, protective peptide analog. J Immunol 175(9):5839–5847PubMedCrossRef
91.
Zurück zum Zitat Zimmer R, Scherbarth HR, Rillo OL, Gomez-Reino JJ, Muller S (2013) Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled phase IIb clinical trial. Ann Rheum Dis 72(11):1830–1835PubMedCentralPubMedCrossRef Zimmer R, Scherbarth HR, Rillo OL, Gomez-Reino JJ, Muller S (2013) Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled phase IIb clinical trial. Ann Rheum Dis 72(11):1830–1835PubMedCentralPubMedCrossRef
92.
Zurück zum Zitat Usmani N, Goodfield M (2007) Efalizumab in the treatment of discoid lupus erythematosus. Arch Dermatol 143(7):873–877PubMedCrossRef Usmani N, Goodfield M (2007) Efalizumab in the treatment of discoid lupus erythematosus. Arch Dermatol 143(7):873–877PubMedCrossRef
95.
Zurück zum Zitat Nossent J, Kiss E, Rozman B, Pokorny G, Vlachoyiannopoulos P, Olesinska M, Marchesoni A, Mosca M, Pai S, Manger K, Schneider M, Nielsen H, van Vollenhoven R, Swaak T (2010) Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus. Lupus 19(8):949–956PubMedCrossRef Nossent J, Kiss E, Rozman B, Pokorny G, Vlachoyiannopoulos P, Olesinska M, Marchesoni A, Mosca M, Pai S, Manger K, Schneider M, Nielsen H, van Vollenhoven R, Swaak T (2010) Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus. Lupus 19(8):949–956PubMedCrossRef
96.
Zurück zum Zitat Urowitz MB, Feletar M, Bruce IN, Ibanez D, Gladman DD (2005) Prolonged remission in systemic lupus erythematosus. J Rheumatol 32(8):1467–1472PubMed Urowitz MB, Feletar M, Bruce IN, Ibanez D, Gladman DD (2005) Prolonged remission in systemic lupus erythematosus. J Rheumatol 32(8):1467–1472PubMed
97.
Zurück zum Zitat Urowitz MB, Gladman DD, Ibanez D, Fortin PR, Bae SC, Gordon C, Clarke A, Bernatsky S, Hanly JG, Isenberg D, Rahman A, Sanchez-Guerrero J, Wallace DJ, Ginzler E, Alarcon GS, Merrill JT, Bruce IN, Sturfelt G, Nived O, Steinsson K, Khamashta M, Petri M, Manzi S, Ramsey-Goldman R, Dooley MA, van Vollenhoven RF, Ramos M, Stoll T, Zoma A, Kalunian K, Aranow C (2012) Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort. Arthritis Care Res 64(1):132–137CrossRef Urowitz MB, Gladman DD, Ibanez D, Fortin PR, Bae SC, Gordon C, Clarke A, Bernatsky S, Hanly JG, Isenberg D, Rahman A, Sanchez-Guerrero J, Wallace DJ, Ginzler E, Alarcon GS, Merrill JT, Bruce IN, Sturfelt G, Nived O, Steinsson K, Khamashta M, Petri M, Manzi S, Ramsey-Goldman R, Dooley MA, van Vollenhoven RF, Ramos M, Stoll T, Zoma A, Kalunian K, Aranow C (2012) Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort. Arthritis Care Res 64(1):132–137CrossRef
Metadaten
Titel
Systemic lupus erythematosus: a therapeutic challenge for the XXI century
verfasst von
Manuel F. Ugarte-Gil
Graciela S Alarcón
Publikationsdatum
01.04.2014
Verlag
Springer London
Erschienen in
Clinical Rheumatology / Ausgabe 4/2014
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-014-2531-4

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