Novel and emerging treatment strategies for lupus nephritis

References

• Yap DY, Tang CS, Ma MK, et al. Survival analysis and causes of mortality in patients with lupus nephritis. Nephrol Dial Transplant. 2012;27(8):3248–3254.
   Google Scholar
• Mok CC, Kwok RCL, Yip PSF. Effect of renal disease on the standardized mortality ratio and life expectancy of patients with systemic lupus erythematosus. Arthritis Rheumatism. 2013;65(8):2154–2160. in press.
   Google Scholar
• Mok CC, Ho LY, Chan KL, et al. Trend of survival of a cohort of Chinese patients with systemic lupus erythematosus over 25 years. Front Med (Lausanne). 2020;7:552.
   Google Scholar
• KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4S):S1–S276.
   Google Scholar
• Fanouriakis A, Kostopoulou M, Cheema K, 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):713–723.
   Google Scholar
• Chan TM, Li FK, Tang CS, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou nephrology study group. N Engl J Med. 2000;343(16):1156–1162.
   Google Scholar
• Mok CC, Lau CS, Wong RW. Risk factors for avascular bone necrosis in systemic lupus erythematosus. Br J Rheumatol. 1998;37(8):895–900.
   Google Scholar
• Mok CC, Ying KY, Ng WL, et al. Long-term outcome of diffuse proliferative lupus glomerulonephritis treated with cyclophosphamide. Am J Med. 2006;119(4):355 e325–333.
   Google Scholar
• Mok CC, Lau CS, Wong RW. Risk factors for ovarian failure in patients with systemic lupus erythematosus receiving cyclophosphamide therapy. Arthritis Rheum. 1998;41(5):831–837.
   Google Scholar
• Bernatsky S, Joseph L, Boivin J-F, et al. The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case-cohort study. Ann Rheum Dis. 2008;67(1):74–79.
   Google Scholar
• Mok CC. Pathogenesis of systemic lupus erythematosus. J Clin Pathol. 2003;56(7):481–490.
   Google Scholar
• Yap DYH, Chan TM. B cell abnormalities in systemic lupus erythematosus and lupus nephritis-role in pathogenesis and effect of immunosuppressive treatments. Int J Mol Sci. 2019;20(24):6231.
   Google Scholar
• Yap DYH, Lai KN. The role of cytokines in the pathogenesis of systemic lupus erythematosus - from bench to bedside. Nephrology (Carlton). 2013;18(4):243–255.
   Google Scholar
• Vlahakos DV, Foster MH, Adams S, et al. Anti-DNA antibodies form immune deposits at distinct glomerular and vascular sites. Kidney Int. 1992;41(6):1690–1700.
   Google Scholar
• Tsao BP, Ohnishi K, Cheroutre H, et al. Failed self-tolerance and autoimmunity in IgG anti-DNA transgenic mice. J Immunol. 1992;149(1):350–358.
   Google Scholar
• Riley JK, Sliwkowski MX. CD20: a gene in search of a function. Semin Oncol. 2000;27(6 Suppl 12):17–24.
   Google Scholar
• Tsokos GC. B cells, be gone — B-cell depletion in the treatment of rheumatoid arthritis. N Engl J Med. 2004;350(25):2546–2548.
   Google Scholar
• Rovin BH, Furie R, Latinis K, et al., Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the lupus nephritis assessment with Rituximab study. Arthritis Rheumatism. 2012;64(4):1215–1226.
   Google Scholar
• Freeman CL, Sehn LH. A tale of two antibodies: obinutuzumab versus rituximab. Br J Haematol. 2018;182(1):29–45.
   Google Scholar
• Furie R, Cascino MD, Garg JP, et al. B-cell depletion and response in a randomized, controlled trial of obinutuzumab for proliferative lupus nephritis lupus science & medicine. lupus Sci Med. 2020;7(Suppl_1):A27.
   Google Scholar
• Furie RA, Aroca G, Cascino MD, et al., B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022;81(1):100–107.
   Google Scholar
• Kansal R, Richardson N, Neeli I, et al. Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. Sci Transl Med. 2019;11(482):eaav1648.
   Google Scholar
• Mougiakakos D, Kronke G, Volkl S, et al. CD19-Targeted CAR T Cells in refractory systemic lupus erythematosus. N Engl J Med. 2021;385(6):567–569.
   Google Scholar
• Li W, Chen W, Sun L. An update for mesenchymal stem cell therapy in lupus nephritis. Kidney Diseases. 2021;7(2):79–89.
   Google Scholar
• Alexander T, Sarfert R, Klotsche J, et al. The proteasome inhibitior bortezomib depletes plasma cells and ameliorates clinical manifestations of refractory systemic lupus erythematosus. Ann Rheum Dis. 2015;74(7):1474–1478.
   Google Scholar
• Zhang H, Liu Z, Huang L, et al. The short-term efficacy of bortezomib combined with glucocorticoids for the treatment of refractory lupus nephritis. Lupus. 2017;26(9):952–958.
   Google Scholar
• Furie R, Bomba D, Dall’Era M, et al. Treatment of systemic lupus erythematosus patients with the immunoproteosome inhibitor KZr-616: results from the first 2 cohorts of an open-label phase 1b dose escalation trial. Ann Rheum Dis. 2019;78:A776.
   Google Scholar
• Ostendorf L, Burns M, Durek P, et al. Targeting CD38 with daratumumab in refractory systemic lupus erythematosus. N Engl J Med. 2020;383(12):1149–1155.
   Google Scholar
• Merrill JT, Werth VP, Furie R, et al. Phase 2 trial of iberdomide in systemic lupus erythematosus. N Engl J Med. 2022;386(11):1034–1045.
   Google Scholar
• Hoffman W, Lakkis FG, Chalasani GBC. B cells, antibodies, and more. Clin J Am Soc Nephrol. 2016;11(1):137–154.
   Google Scholar
• Furie R, Rovin BH, Houssiau F, et al., Two-Year, randomized, controlled trial of belimumab in Lupus Nephritis. N Engl J Med. 2020;383(12):1117–1128.
   Google Scholar
• Navarra SV, Guzman RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721–731.
   Google Scholar
• Furie R, Petri M, Zamani O, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3918–3930.
   Google Scholar
• Dooley MA, Houssiau F, Aranow C, et al. Effect of belimumab treatment on renal outcomes: results from the phase 3 belimumab clinical trials in patients with SLE. Lupus. 2013;22(1):63–72.
   Google Scholar
• Stohl W, Hiepe F, Latinis KM, et al. Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum. 2012;64(7):2328–2337.
   Google Scholar
• Ginzler E, Guedes Barbosa LS, D’Cruz D, et al. Phase III / IV, randomized, fifty-two –week study of the efficacy and safety of belimumab in patients of Black African ancestry with systemic lupus erythematosus. Arthritis Rheumatol. 2022;74(1):112–123.
   Google Scholar
• Yemil Atisha-Fregoso Y, Malkiel S, Harris KM, et al. Phase II Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis. Arthritis Rheumatol. 2018;73(1):121–131.
   Google Scholar
• Kraaij T, Kamerling SWA, de Rooij ENM, et al. The NET-effect of combining rituximab with belimumab in severe systemic lupus erythematosus. J Autoimmun. 2018;91:45–54.
   Google Scholar
• Teng YKO, Bruce IN, Diamond B, et al. Phase III, multicentre, randomised, double-blind, placebo-controlled, 104-week study of subcutaneous belimumab administered in combination with rituximab in adults with systemic lupus erythematosus (SLE): BLISS-BELIEVE study protocol. BMJ Open. 2019;9(3):e025687.
   Google Scholar
• Zuercher AW, Spirig R, Baz Morelli A, et al. Next-generation Fc receptor–targeting biologics for autoimmune diseases. Autoimmun Rev. 2019;18(10):102366.
   Google Scholar
• Yap DYH, Hai J, Lee PCH, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of HBM9161, a novel FcRn inhibitor, in a phase I study for healthy Chinese volunteers. Clin Transl Sci. 2021;14(5):1769–1779.
   Google Scholar
• Howard JF Jr., Bril V, Burns TM, et al. Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis. Neurology. 2019;92(23):e2661–e2673.
   Google Scholar
• Mak A, Kow NY. The pathology of T cells in systemic lupus erythematosus. J Immunol Res. 2014;2014:419029.
   Google Scholar
• Dutta D, Barr VA, Akpan I, et al. Recruitment of calcineurin to the TCR positively regulates T cell activation. Nat Immunol. 2017;18(2):196–204.
   Google Scholar
• Faul C, Donnelly M, Merscher-Gomez S, et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med. 2008;14(9):931–938.
   Google Scholar
• Mok CC, Tong KH, To CH, et al. Tacrolimus for induction therapy of diffuse proliferative lupus nephritis: an open-labeled pilot study. Kidney Int. 2005;68(2):813–817.
   Google Scholar
• Chen W, Tang X, Liu Q, et al. Short-term outcomes of induction therapy with tacrolimus versus cyclophosphamide for active lupus nephritis: a multicenter randomized clinical trial. Am J Kidney Dis. 2011;57(2):235–244.
   Google Scholar
• Tanaka H, Watanabe S, Aizawa-Yashiro T, et al. Long-term tacrolimus-based immunosuppressive treatment for young patients with lupus nephritis: a prospective study in daily clinical practice. Nephron Clin Pract. 2013;121(3–4):c165–173.
   Google Scholar
• Mok CC, To CH, Yu KL, et al. Combined low-dose mycophenolate mofetil and tacrolimus for lupus nephritis with suboptimal response to standard therapy: a 12-month prospective study. Lupus. 2013;22(11):1135–1141.
   Google Scholar
• Kise T, Yoshimura H, Fukuyama S, et al. Successful treatment with mycophenolate mofetil and tacrolimus in juvenile severe lupus nephritis. Case Rep Pediatr. 2015;2015:651803.
   Google Scholar
• Liu Z, Zhang H, Liu Z, et al. Multitarget therapy for induction treatment of lupus nephritis: a randomized trial. Ann Intern Med. 2015;162(1):18–26.
   Google Scholar
• Mok CC, Ying KY, Yim CW, et al. Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: a randomised controlled trial and long-term follow-up. Ann Rheum Dis. 2016;75(1):30–36.
   Google Scholar
• Zhang H, Liu Z, Zhou M, et al. Multitarget therapy for maintenance treatment of lupus nephritis. J Am Soc Nephrol. 2017;28(12):3671–3678.
   Google Scholar
• Choi CB, Won S, Bae SC. Outcomes of multitarget therapy using mycophenolate mofetil and tacrolimus for refractory or relapsing lupus nephritis. Lupus. 2018;27(6):1007–1011.
   Google Scholar
• Park DJ, Kang JH, Lee KE, et al. Efficacy and safety of mycophenolate mofetil and tacrolimus combination therapy in patients with lupus nephritis: a nationwide multicentre study. Clin Exp Rheumatol. 2019;37(1):89–96.
   Google Scholar
• Mok CC, Ho LY, Ying SKY, et al. Long-term outcome of a randomised controlled trial comparing tacrolimus with mycophenolate mofetil as induction therapy for active lupus nephritis. Ann Rheum Dis. 2020;79(8):1070–1076.
   Google Scholar
• Mok CC. Calcineurin inhibitors in systemic lupus erythematosus. Best Pract Res Clin Rheumatol. 2017;31(3):429–438.
   Google Scholar
• Sin FE, Isenberg D. An evaluation of voclosporin for the treatment of lupus nephritis. Expert Opin Pharmacother. 2018;19(14):1613–1621.
   Google Scholar
• Dorner T, Furie R. Novel paradigms in systemic lupus erythematosus. Lancet. 2019;393(10188):2344–2358.
   Google Scholar
• Rovin BH, Solomons N, Pendergraft WF 3rd, 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;95:219–231.
   Google Scholar
• Teng YK, Parikh SV, Saxena A, et al. Aurora phase 3 study demonstrates voclosporin statistical superiority over standard of care in lupus nephritis (LN). Lupus Sci Med. 2020;7:A14.
   Google Scholar
• Rovin BH, Teng YKO, Ginzler EM, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (Aurora 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2021;(10289): 2070–2080. DOI: 10.1016/S0140-6736(21)00578-X.
   Google Scholar
• Yap DY, Ma MK, Mok MM, et al. Long-term data on tacrolimus treatment in lupus nephritis. Rheumatology (Oxford). 2014;53:2232–2237.
   Google Scholar
• Yap DYH, Li PH, Tang C, et al. Long-term results of triple immunosuppression with tacrolimus added to mycophenolate and corticosteroids in the treatment of lupus nephritis. Kidney Int Rep. 2022;7:516–525.
   Google Scholar
• Mihara M, Tan I, Chuzhin Y, et al. CTLA4Ig inhibits T cell-dependent B-cell maturation in murine systemic lupus erythematosus. J Clin Invest. 2000;106:91–101.
   Google Scholar
• Waterhouse P, Penninger JM, Timms E, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995;270:985–988.
   Google Scholar
• Dall’Era M, Davis J. CTLA4Ig: a novel inhibitor of costimulation. Lupus. 2004;13(5):372–376.
   Google Scholar
• Daikh DI, Wofsy D. Cutting edge: reversal of murine lupus nephritis with CTLA4Ig and cyclophosphamide. J Immunol. 2001;166(5):2913–2916.
   Google Scholar
• Furie R, Nicholls K, Cheng -T-T, et al. Efficacy and safety of Abatacept in lupus nephritis: a twelve-month, randomized, double-blind study. Arthritis Rheumatol. 2014;66(2):379–389.
   Google Scholar
• Furie R, Dooley MA, Wofsy D, et al. A phase iii randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of Abatacept or placebo on standard of care in patients with active class iii or iv lupus nephritis. Ann Rheum Dis. 2018;77:A176.
   Google Scholar
• Yu -C-C, Fornoni A, Weins A, et al. Abatacept in B7-1–positive proteinuric kidney disease. N Engl J Med. 2013;369(25):2416–2423.
   Google Scholar
• Reiser J, von Gersdorff G, Loos M, et al. Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest. 2004;113(10):1390–1397.
   Google Scholar
• Furie R, Bruce I, Dorner T, et al. Efficacy and safety of dapirolizumab pegol (DZP) in patients with moderately to severely active systemic lupus erythematosus (SLE): a randomized, placebo (PBO)-controlled study. Ann Rheum Dis. 2019;78:775–776.
   Google Scholar
• Furie RA, Morand EF, Bruce IN, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol. 2019;1(4):e208–219.
   Google Scholar
• Morand EF, Furie R, Tanaka Y, et al. Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med. 2020;382(3):211–221.
   Google Scholar
• Jayne D, Rovin B, Mysler E, et al. POS0690 Randomized, controlled, phase 2 trial of type 1 ifn inhibitor anifrolumab in patients with active proliferative lupus nephritis. Ann Rheum Dis. 2021;80(Suppl 1):592.
   Google Scholar
• Humrich JY, Morbach H, Undeutsch R, et al. Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus. Proc Natl Acad Sci U S A. 2010;107(1):204–209.
   Google Scholar
• Humrich JY, Riemekasten G. Low-dose IL-2 therapy — a complex scenario that remains to be further explored. Nat Rev Rheumatol. 2017;13(6):386.
   Google Scholar
• He J, Zhang X, Wei Y, et al. Low-dose interleukin-2 treatment selectively modulates CD4+ T cell subsets in patients with systemic lupus erythematosus. Nat Med. 2016;22(9):991–993.
   Google Scholar
• von Spee-Mayer C, Siegert E, Abdirama D, et al. Low-dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus. Ann Rheum Dis. 2016;75(7):1407–1415.
   Google Scholar
• He J, Zhang R, Shao M, et al. Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2020;79(1):141–149.
   Google Scholar
• Sciascia S, Radin M, Yazdany J, et al. Expanding the therapeutic options for renal involvement in lupus: eculizumab, available evidence. Rheumatol Int. 2017;37(8):1249–1255.
   Google Scholar
• Wallace DJ, Furie RA, Tanaka Y, et al. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2018;392(10143):222–231.
   Google Scholar
• Kahl L, Patel J, Layton M, et al. Safety, tolerability, efficacy and pharmacodynamics of the selective JAK1 inhibitor GSK2586184 in patients with systemic lupus erythematosus. Lupus. 2016;25(13):1420–1430.
   Google Scholar
• van Vollenhoven RF, Layton M, Kahl L, et al. DRESS syndrome and reversible liver function abnormalities in patients with systemic lupus erythematosus treated with the highly selective JAK-1 inhibitor GSK2586184. Lupus. 2015;24(6):648–649.
   Google Scholar
• Isenberg D, Furie R, Jones N, et al. Efficacy, safety, and pharmacodynamic Effects of the Bruton’s Tyrosine Kinase Inhibitor, Fenebrutinib (GDC-0853), in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis Rheumatol. 2019;73(10):1835–1846.
   Google Scholar
• Zhang C, Chan CCY, Cheung KF, et al. Effect of mycophenolate and rapamycin on renal fibrosis in lupus nephritis. Clin Sci (Lond). 2019;133(15):1721–1744.
   Google Scholar
• Alperovich G, Rama I, Lloberas N, et al. New immunosuppresor strategies in the treatment of murine lupus nephritis. Lupus. 2007;16(1):18–24.
   Google Scholar
• Lui SL, Yung S, Tsang R, et al. Rapamycin prevents the development of nephritis in lupus-prone NZB/W F 1 mice. Lupus. 2008;17(4):305–313.
   Google Scholar
• Lui SL, Tsang R, Chan KW, et al. Rapamycin attenuates the severity of established nephritis in lupus-prone NZB/W F1 mice. Nephrol Dial Transplant. 2008;23(9):2768–2776.
   Google Scholar
• Stylianou K, Petrakis I, Mavroeidi V, et al. The PI3K/Akt/mTOR pathway is activated in murine lupus nephritis and downregulated by rapamycin. Nephrol Dial Transplant. 2011;26(2):498–508.
   Google Scholar
• Yap DY, Ma MK, Tang CS, et al. Proliferation signal inhibitors in the treatment of lupus nephritis: preliminary experience. Nephrology (Carlton). 2012;17(8):676–680.
   Google Scholar
• Yap DYH, Tang C, Chan GCW, et al. Longterm data on sirolimus treatment in patients with lupus nephritis. J Rheumatol. 2018;45(12):1663–1670.
   Google Scholar
• Peng L, Wu C, Hong R, et al. Clinical efficacy and safety of sirolimus in systemic lupus erythematosus: a real-world study and meta-analysis. Ther Adv Musculoskelet Dis. 2020;12:1759720X20953336.
   Google Scholar