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Immunotherapeutics – Product Review

Belimumab for systemic lupus erythematosus – Focus on lupus nephritis

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Article: 2072143 | Received 03 Jan 2022, Accepted 27 Apr 2022, Published online: 19 May 2022

References

  • Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011;365(22):2110–17. doi:10.1056/NEJMra1100359.
  • Olsen NJ, Karp DR. Autoantibodies and SLE—the threshold for disease. Nat Rev Rheumatol. 2014;10(3):181–86. doi:10.1038/nrrheum.2013.184.
  • Munoz LE, van Bavel C, Franz S, Berden J, Herrmann M, van der Vlag J. Apoptosis in the pathogenesis of systemic lupus erythematosus. Lupus. 2008;17(5):371–75. doi:10.1177/0961203308089990.
  • Nagata S, Hanayama R, Kawane K. Autoimmunity and the clearance of dead cells. Cell. 2010;140(5):619–30. doi:10.1016/j.cell.2010.02.014.
  • Baumann I, Kolowos W, Voll RE, Manger B, Gaipl U, Neuhuber WL, Kirchner T, Kalden JR, Herrmann M. Impaired uptake of apoptotic cells into tingible body macrophages in germinal centers of patients with systemic lupus erythematosus. Arthritis Rheum. 2002;46(1):191–201. doi:10.1002/1529-0131(200201)46:1<191:AID-ART10027>3.0.CO;2-K.
  • Tipton CM, Fucile CF, Darce J, Chida A, Ichikawa T, Gregoretti I, Schieferl S, Hom J, Jenks S, Feldman RJ, et al. Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus. Nat Immunol. 2015;16(7):755–65. doi:10.1038/ni.3175.
  • Leonard D, Eloranta M-L, Hagberg N, Berggren O, Tandre K, Alm G, Rönnblom L. Activated T cells enhance interferon-α production by plasmacytoid dendritic cells stimulated with RNA-containing immune complexes. Ann Rheum Dis. 2016;75(9):1728–34. doi:10.1136/annrheumdis-2015-208055.
  • Hoover PJ, Costenbader KH. Insights into the epidemiology and management of lupus nephritis from the US rheumatologist’s perspective. Kidney Int. 2016;90(3):487–92. doi:10.1016/j.kint.2016.03.042.
  • Moroni G, Depetri F, Ponticelli C. Lupus nephritis: when and how often to biopsy and what does it mean? J Autoimmun. 2016;74:27–40. doi:10.1016/j.jaut.2016.06.006.
  • Davidson A. What is damaging the kidney in lupus nephritis? Nat Rev Rheumatol. 2016;12(3):143–53. doi:10.1038/nrrheum.2015.159.
  • Kaul A, Gordon C, Crow MK, Touma Z, Urowitz MB, van Vollenhoven R, Ruiz-Irastorza G, Hughes G. Systemic lupus erythematosus. Nat Rev Dis Primers. 2016;2(1):16039. doi:10.1038/nrdp.2016.39.
  • Tamirou F, Houssiau FA. Management of lupus nephritis. J Clin Med. 2021;10(4):670. doi:10.3390/jcm10040670.
  • Weening JJ, D’-Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, Balow JE, Bruijn JANA, Cook T, Ferrario F, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004;65(2):521–30. doi:10.1111/j.1523-1755.2004.00443.x.
  • Bajema IM, Wilhelmus S, Alpers CE, Bruijn JA, Colvin RB, Cook HT, D’-Agati VD, Ferrario F, Haas M, Jennette JC, et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int. 2018;93(4):789–96. doi:10.1016/j.kint.2017.11.023.
  • Hong S, Healy H, Kassianos AJ. The emerging role of renal tubular epithelial cells in the immunological pathophysiology of lupus nephritis. Front Immunol. 2020;11:578952. doi:10.3389/fimmu.2020.578952.
  • Stohl W, Hilbert DM. The discovery and development of belimumab: the anti-BLyS–lupus connection. Nat Biotechnol. 2012;30(1):69–77. doi:10.1038/nbt.2076.
  • Ruiz-Irastorza G, Bertsias G. Treating systemic lupus erythematosus in the 21st century: new drugs and new perspectives on old drugs. Rheumatology. 2020;59:v69–81. doi:10.1093/rheumatology/keaa403.
  • Davidson A. The rationale for BAFF inhibition in systemic lupus erythematosus. Curr Rheumatol Rep. 2012;14(4):295–302. doi:10.1007/s11926-012-0258-2.
  • Manzi S, Sánchez-Guerrero J, Merrill JT, Furie R, Gladman D, Navarra SV, Ginzler EM, D’-Cruz DP, Doria A, Cooper S, et al. 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. 2012;71(11):1833–38. doi:10.1136/annrheumdis-2011-200831.
  • Stohl W, Schwarting A, Okada M, Scheinberg M, Doria A, Hammer AE, Kleoudis C, Groark J, Bass D, Fox NL, et al. Efficacy and safety of subcutaneous belimumab in systemic lupus erythematosus: a fifty-two–week randomized, double-blind, placebo-controlled study. Arthritis Rheumatol. 2017;69(5):1016–27. doi:10.1002/art.40049.
  • Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzová D, Sanchez-Guerrero J, Schwarting A, Merrill JT, Chatham WW, 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):3918–30. doi:10.1002/art.30613.
  • Navarra SV, Guzmán RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, Li EKM, Thomas M, Kim H-Y, León MG, 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):721–31. doi:10.1016/S0140-6736(10)61354-2.
  • Furie R, Rovin BH, Houssiau F, Malvar A, Teng YKO, Contreras G, Amoura Z, Yu X, Mok C-C, Santiago MB, et al. Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med. 2020;383(12):1117–28. doi:10.1056/NEJMoa2001180.
  • Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, Cervera R, Doria A, Gordon C, Govoni M, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736–45. doi:10.1136/annrheumdis-2019-215089.
  • Fanouriakis A, Kostopoulou M, Cheema K, Anders H-J, Aringer M, Bajema I, Boletis J, Frangou E, Houssiau FA, Hollis J, 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. doi:10.1136/annrheumdis-2020-216924.
  • Ugarte-Gil MF, Mak A, Leong J, Dharmadhikari B, Kow NY, Reátegui-Sokolova C, Elera-Fitzcarrald C, Aranow C, Arnaud L, Askanase AD, et al. Impact of glucocorticoids on the incidence of lupus-related major organ damage: a systematic literature review and meta-regression analysis of longitudinal observational studies. Lupus Sci Med. 2021;8(1):e000590. doi:10.1136/lupus-2021-000590.
  • Porta SV, Ugarte-Gil MF, García-de la Torre I, Bonfá E, Gómez-Puerta JA, Arnaud L, Cardiel MH, Alarcón GS, Pons-Estel BA, Pons-Estel G. Controversies in systemic lupus erythematosus: are we treating our patients adequately? J Clin Rheumatol. 2022;28(2):e651–e658. doi:10.1097/RHU.0000000000001803.
  • Kado R, McCune WJ. Ovarian protection with gonadotropin-releasing hormone agonists during cyclophosphamide therapy in systemic lupus erythematosus. Best Pract Res Clin Obstet Gynaecol. 2020;64:97–106. doi:10.1016/j.bpobgyn.2019.10.008.
  • Houssiau FA, Vasconcelos C, D’-Cruz D, Sebastiani GD, Garrido Ed EDR, Danieli MG, Abramovicz D, Blockmans D, Mathieu A, Direskeneli H, 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. doi:10.1002/art.10461.
  • González RF, Abida R, Gisca E, Duarte L, Isenberg DA. Can we predict if patients will require more than one cycle of rituximab? Rheumatology (Oxford). 2021:keab527. doi:10.1093/rheumatology/keab527.
  • Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, Maciuca R, Zhang D, Garg JP, Brunetta P, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the lupus nephritis assessment with Rituximab study. Arthritis Rheum. 2012;64(4):1215–26. doi:10.1002/art.34359.
  • Merrill JT, Neuwelt CM, Wallace DJ, Shanahan JC, Latinis KM, Oates JC, Utset TO, Gordon C, Isenberg DA, Hsieh H-J, et al. 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. 2010;62(1):222–33. doi:10.1002/art.27233.
  • Rydén-Aulin M, Boumpas D, Bultink I, Callejas Rubio JL, Caminal-Montero L, Castro A, Colodro Ruiz A, Doria A, Dörner T, Gonzalez-Echavarri C, et al. Off-Label use of rituximab for systemic lupus erythematosus in Europe. Lupus Sci Med. 2016;3(1):e000163. doi:10.1136/lupus-2016-000163.
  • Kraaij T, Bredewold OW, Trompet S, Huizinga TWJ, Rabelink TJ, de Craen AJM, Teng YKO. TAC-TIC use of tacrolimus-based regimens in lupus nephritis. Lupus Sci Med. 2016;3(1):e000169. doi:10.1136/lupus-2016-000169.
  • Tamirou F, Lauwerys BR, Dall’-Era M, Mackay M, Rovin B, Cervera R, Houssiau FA. MAINTAIN nephritis trial investigators. A proteinuria cut-off level of 0.7 g/day after 12 months of treatment best predicts long-term renal outcome in lupus nephritis: data from the MAINTAIN nephritis trial. Lupus Sci Med. 2015;2(1):e000123. doi:10.1136/lupus-2015-000123.
  • Furie RA, Morand EF, Bruce IN, Manzi S, Kalunian KC, Vital EM, Ford TL, Gupta R, Hiepe F, Santiago M, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol. 2019;1:e208–19. doi:10.1016/S2665-9913(19)30076-1.
  • Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, Richez C, Bae S-C, Brohawn PZ, Pineda L, Berglind A, et al. Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med. 2020;382(3):211–21. doi:10.1056/NEJMoa1912196.
  • Cooles FAH, Isaacs JD. The interferon gene signature as a clinically relevant biomarker in autoimmune rheumatic disease. Lancet Rheumatol. 2022;4(1):e61–72. doi:10.1016/S2665-9913(21)00254-X.
  • Vital EM, Merrill JT, Morand EF, Furie RA, Bruce IN, Tanaka Y, Manzi S, Kalunian KC, Kalyani RN, Streicher K, et al. Anifrolumab efficacy and safety by type I interferon gene signature and clinical subgroups in patients with SLE: post hoc analysis of pooled data from two phase III trials. Ann Rheum Dis. 2022: annrheumdis-2021-221425. doi:10.1136/annrheumdis-2021-221425.
  • Deeks ED. Anifrolumab: first approval. Drugs. 2021;81(15):1795–802. doi:10.1007/s40265-021-01604-z.
  • Tanaka Y, Tummala R. Anifrolumab, a monoclonal antibody to the type I interferon receptor subunit 1, for the treatment of systemic lupus erythematosus: an overview from clinical trials. Mod Rheumatol. 2021;31(1):1–12. doi:10.1080/14397595.2020.1812201.
  • Rovin BH, Teng YKO, Ginzler EM, Arriens C, Caster DJ, Romero-Diaz J, Gibson K, Kaplan J, Lisk L, Navarra S, 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;397(10289):2070–80. doi:10.1016/S0140-6736(21)00578-X.
  • Heo Y-A. Voclosporin: first Approval. Drugs. 2021;81(5):605–10. doi:10.1007/s40265-021-01488-z.
  • Rovin BH, Solomons N, Pendergraft WF, Dooley MA, Tumlin J, Romero-Diaz J, Lysenko L, Navarra SV, Huizinga RB, Adzerikho I, 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. doi:10.1016/j.kint.2018.08.025.
  • Bîrsan T, Dambrin C, Freitag DG, Yatscoff RW, Morris RE. The novel calcineurin inhibitor ISA247: a more potent immunosuppressant than cyclosporine in vitro. Transpl Int. 2005;17(12):767–71. doi:10.1111/j.1432-2277.2004.tb00509.x.
  • Li Y, Palmisano M, Sun D, Zhou S. Pharmacokinetic disposition difference between cyclosporine and voclosporin drives their distinct efficacy and safety profiles in clinical studies. Clin Pharmacol. 2020;12:83–96. doi:10.2147/CPAA.S255789.
  • Furie RA, Aroca G, Cascino MD, Garg JP, Rovin BH, Alvarez A, Fragoso-Loyo H, Zuta-Santillan E, Schindler T, Brunetta P, 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):100–07. doi:10.1136/annrheumdis-2021-220920.
  • Jayne D, Rovin B, Mysler EF, Furie RA, Houssiau FA, Trasieva T, Knagenhjelm J, Schwetje E, Chia YL, Tummala R, et al. Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. Ann Rheum Dis. 2022;81(4):496–506. doi:10.1136/annrheumdis-2021-221478.
  • Liossis SN, Staveri C. What’s new in the treatment of systemic lupus erythematosus. Front Med (Lausanne). 2021;8:655100. doi:10.3389/fmed.2021.655100.
  • Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey‐goldman R, Smolen JS, Wofsy D, Boumpas DT, Kamen DL, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019;71(9):1400–12. doi:10.1002/art.40930.
  • Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, Ambrose C, Lawton P, Bixler S, Acha-Orbea H, et al. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med. 1999;189(11):1747–56. doi:10.1084/jem.189.11.1747.
  • Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P, Soppet D, Charters M, Gentz R, Parmelee D, et al. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 1999;285(5425):260–63. doi:10.1126/science.285.5425.260.
  • Shu HB, Hu WH, Johnson H. TALL-1 is a novel member of the TNF family that is down-regulated by mitogens. J Leukoc Biol. 1999;65(5):680–83. doi:10.1002/jlb.65.5.680.
  • Mukhopadhyay A, Ni J, Zhai Y, Yu GL, Aggarwal BB. Identification and characterization of a novel cytokine, THANK, aTNF homologue that activates apoptosis, nuclear factor-κB, and c-Jun NH2-terminal kinase. J Biol Chem. 1999;274(23):15978–81. doi:10.1074/jbc.274.23.15978.
  • Mackay F, Figgett WA, Saulep D, Lepage M, Hibbs ML. B-Cell stage and context-dependent requirements for survival signals from BAFF and the B-cell receptor. Immunol Rev. 2010;237(1):205–25. doi:10.1111/j.1600-065X.2010.00944.x.
  • Vincent FB, Northcott M, Hoi A, Mackay F, Morand EF. Association of serum B cell activating factor from the tumour necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) with central nervous system and renal disease in systemic lupus erythematosus. Lupus. 2013;22(9):873–84. doi:10.1177/0961203313496302.
  • Petri M, Stohl W, Chatham W, McCune WJ, Chevrier M, Ryel J, Recta V, Zhong J, Freimuth W. Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum. 2008;58(8):2453–59. doi:10.1002/art.23678.
  • Friebus-Kardash J, Branco L, Ribi C, Chizzolini C, Huynh-Do U, Dubler D, Roux-Lombard P, Dolff S, Kribben A, Eisenberger U, et al. Immune complexes containing serum B-cell activating factor and immunoglobulin G correlate with disease activity in systemic lupus erythematosus. Nephrol Dial Transplant. 2018;33(1):54–64. doi:10.1093/ndt/gfx220.
  • Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P, Tschopp J, Browning JL. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999;190(11):1697–710. doi:10.1084/jem.190.11.1697.
  • Rawlings DJ, Metzler G, Wray-Dutra M, Jackson SW. Altered B cell signalling in autoimmunity. Nat Rev Immunol. 2017;17(7):421–36. doi:10.1038/nri.2017.24.
  • Heltemes-Harris L, Liu X, Manser T. Progressive surface B cell antigen receptor down-regulation accompanies efficient development of antinuclear antigen B cells to mature, follicular phenotype. J Immunol. 2004;172(2):823–33. doi:10.4049/jimmunol.172.2.823.
  • Jackson SW, Davidson A. BAFF inhibition in SLE—Is tolerance restored? Immunol Rev. 2019;292(1):102–19. doi:10.1111/imr.12810.
  • Benson MJ, Dillon SR, Castigli E, Geha RS, Xu S, Lam K-P, Noelle RJ. Cutting edge: the dependence of plasma cells and independence of memory B cells on BAFF and APRIL. J Immunol. 2008;180(6):3655–59. doi:10.4049/jimmunol.180.6.3655.
  • Huang W, Quach TD, Dascalu C, Liu Z, Leung T, Byrne-Steele M, Pan W, Yang Q, Han J, Lesser M, et al. Belimumab promotes negative selection of activated autoreactive B cells in systemic lupus erythematosus patients. JCI Insight. 2018;3(17). doi:10.1172/jci.insight.122525.
  • Ng LG, Sutherland APR, Newton R, Qian F, Cachero TG, Scott ML, Thompson JS, Wheway J, Chtanova T, Groom J, et al. B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells. J Immunol. 2004;173(2):807–17. doi:10.4049/jimmunol.173.2.807.
  • Rother N, van der Vlag J. Disturbed T cell signaling and altered Th17 and regulatory T cell subsets in the pathogenesis of systemic lupus erythematosus. Front Immunol. 2015;6:610. doi:10.3389/fimmu.2015.00610.
  • Peng SL. Altered T and B lymphocyte signaling pathways in lupus. Autoimmun Rev. 2009;8(3):179–83. doi:10.1016/j.autrev.2008.07.040.
  • Schwarting A, Relle M, Meineck M, Föhr B, Triantafyllias K, Weinmann A, Roth W, Weinmann-Menke J. Renal tubular epithelial cell-derived BAFF expression mediates kidney damage and correlates with activity of proliferative lupus nephritis in mouse and men. Lupus. 2018;27(2):243–56. doi:10.1177/0961203317717083.
  • Suso JP, Posso-Osorio I, Jiménez CA, Naranjo-Escobar J, Ospina FE, Sánchez A, Cañas CA, Tobón GJ. Profile of BAFF and its receptors’ expression in lupus nephritis is associated with pathological classes. Lupus. 2018;27(5):708–15. doi:10.1177/0961203317739132.
  • Furie R, Stohl W, Ginzler EM, Becker M, Mishra N, Chatham W, Merrill JT, Weinstein A, McCune WJ, Zhong J, et al. Biologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: a phase I trial in patients with systemic lupus erythematosus. Arthritis Res Ther. 2008;10(5):R109. doi:10.1186/ar2506.
  • Wallace DJ, Stohl W, Furie RA, Lisse JR, McKay JD, Merrill JT, Petri MA, Ginzler EM, Chatham WW, McCune WJ, et al. A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheum. 2009;61(9):1168–78. doi:10.1002/art.24699.
  • Collins CE, Dall’-Era M, Kan H, Macahilig C, Molta C, Koscielny V, Chang DJ. Response to belimumab among patients with systemic lupus erythematosus in clinical practice settings: 24-month results from the OBSErve study in the USA. Lupus Sci Med. 2016;3(1):e000118. doi:10.1136/lupus-2015-000118.
  • Collins CE, Cortes-Hernández J, Garcia MA, von Kempis J, Schwarting A, Touma Z, Kurtinecz M, Gairy K. Real-world effectiveness of belimumab in the treatment of systemic lupus erythematosus: pooled analysis of multi-country data from the OBSErve studies. Rheumatol Ther. 2020;7(4):949–65. doi:10.1007/s40744-020-00243-2.
  • Schwarting A, Schroeder JO, Alexander T, Schmalzing M, Fiehn C, Specker C, Perna A, Cholmakow-Bodechtel C, Koscielny VB, Carnarius H. First real-world insights into belimumab use and outcomes in routine clinical care of systemic lupus erythematosus in Germany: results from the OBSErve Germany study. Rheumatol Ther. 2016;3(2):271–90. doi:10.1007/s40744-016-0047-x.
  • von Kempis J, Duetsch S, Reuschling N, Villiger R, Villiger PM, Vallelian F, Schaer DJ, Mueller RB. Clinical outcomes in patients with systemic lupus erythematosus treated with belimumab in clinical practice settings: a retrospective analysis of results from the OBSErve study in Switzerland. Swiss Medical Weekly [Internet]. 2019 [accessed 2022 Mar 22]. https://smw.ch/article/doi/smw.2019.20022.
  • Touma Z, Sayani A, Pineau CA, Fortin I, Matsos M, Ecker GA, Chow A, Iczkovitz S. Belimumab use, clinical outcomes and glucocorticoid reduction in patients with systemic lupus erythematosus receiving belimumab in clinical practice settings: results from the OBSErve Canada study. Rheumatol Int. 2017;37(6):865–73. doi:10.1007/s00296-017-3682-9.
  • Dooley MA, Houssiau F, Aranow C, D’-Cruz DP, Askanase A, Roth DA, Zhong ZJ, Cooper S, Freimuth WW, Ginzler EM, 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. doi:10.1177/0961203312465781.
  • Fließer EE, Korsten P, Koziolek MJ, Niewold TB, Patschan D, Müller GA, Patschan SA. Successful treatment of a mycophenolate mofetil-refractory proliferative lupus nephritis with belimumab in a 19-year-old woman. Lupus. 2013;22(14):1523–25. doi:10.1177/0961203313504145.
  • Plüß M, Tampe B, Niebusch N, Zeisberg M, Müller GA, Korsten P. Clinical efficacy of routinely administered belimumab on proteinuria and neuropsychiatric lupus. Front Med (Lausanne). 2020;7:222. doi:10.3389/fmed.2020.00222.
  • Margiotta DPE, Basta F, Batani V, Afeltra A. Belimumab and low-doses of mycophenolate mofetil as induction therapy of class IV lupus nephritis: case series and literature review. BMC Nephrol. 2018;19(1):54. doi:10.1186/s12882-018-0847-z.
  • van Vollenhoven RF, Petri MA, Cervera R, Roth DA, Ji BN, Kleoudis CS, Zhong ZJ, Freimuth W. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis. 2012;71(8):1343–49. doi:10.1136/annrheumdis-2011-200937.
  • Wallace D, Navarra S, Petri M, Gallacher A, Thomas M, Furie R, Levy R, van Vollenhoven R, Cooper S, Zhong Z, et al. Safety profile of belimumab: pooled data from placebo-controlled phase 2 and 3 studies in patients with systemic lupus erythematosus. Lupus. 2013;22(2):144–54. doi:10.1177/0961203312469259.
  • Ginzler EM, Wallace DJ, Merrill JT, Furie RA, Stohl W, Chatham WW, Weinstein A, McKay JD, McCune WJ, Zhong ZJ, et al. Disease control and safety of belimumab plus standard therapy over 7 years in patients with systemic lupus erythematosus. J Rheumatol. 2014;41(2):300–09. doi:10.3899/jrheum.121368.
  • Bruce IN, Urowitz M, van Vollenhoven R, Aranow C, Fettiplace J, Oldham M, Wilson B, Molta C, Roth D, Gordon D. Long-Term organ damage accrual and safety in patients with SLE treated with belimumab plus standard of care. Lupus. 2016;25(7):699–709. doi:10.1177/0961203315625119.
  • Zhang F, Bae S-C, Bass D, Chu M, Egginton S, Gordon D, Roth DA, Zheng J, Tanaka Y. A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea. Ann Rheum Dis. 2018;77(3):355–63. doi:10.1136/annrheumdis-2017-211631.
  • Strand V, Berry P, Lin X, Asukai Y, Punwaney R, Ramachandran S. Long‐term impact of belimumab on health‐related quality of life and fatigue in patients with systemic lupus erythematosus: six years of treatment. Arthritis Care Res. 2019;71(6):829–38. doi:10.1002/acr.23788.
  • Wallace DJ, Ginzler EM, Merrill JT, Furie RA, Stohl W, Chatham WW, Weinstein A, McKay JD, McCune WJ, Petri M, et al. Safety and efficacy of belimumab plus standard therapy for up to thirteen years in patients with systemic lupus erythematosus. Arthritis Rheumatol. 2019;71(7):1125–34. doi:10.1002/art.40861.
  • Urowitz MB, Ohsfeldt RL, Wielage RC, Kelton KA, Asukai Y, Ramachandran S. Organ damage in patients treated with belimumab versus standard of care: a propensity score-matched comparative analysis. Ann Rheum Dis. 2019;78(3):372–79. doi:10.1136/annrheumdis-2018-214043.
  • Gatto M, Saccon F, Zen M, Regola F, Fredi M, Andreoli L, Tincani A, Urban ML, Emmi G, Ceccarelli F, et al. Early disease and low baseline damage as predictors of response to belimumab in patients with systemic lupus erythematosus in a real‐life setting. Arthritis Rheumatol. 2020;72(8):1314–24. doi:10.1002/art.41253.
  • Brunner HI, Abud-Mendoza C, Viola DO, Calvo Penades I, Levy D, Anton J, Calderon JE, Chasnyk VG, Ferrandiz MA, Keltsev V, et al. Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial. Ann Rheum Dis. 2020;79(10):1340–48. doi:10.1136/annrheumdis-2020-217101.
  • van Vollenhoven RF, Navarra SV, Levy RA, Thomas M, Heath A, Lustine T, Adamkovic A, Fettiplace J, Wang M-L, Ji B, et al. Long-Term safety and limited organ damage in patients with systemic lupus erythematosus treated with belimumab: a Phase III study extension. Rheumatology. 2020;59(2):281–91. doi:10.1093/rheumatology/kez279.
  • Urowitz MB, Ohsfeldt RL, Wielage RC, Dever JJ, Zakerifar M, Asukai Y, Ramachandran S, Joshi AV. Comparative analysis of long-term organ damage in patients with systemic lupus erythematosus using belimumab versus standard therapy: a post hoc longitudinal study. Lupus Sci Med. 2020;7(1):e000412. doi:10.1136/lupus-2020-000412.
  • Ginzler E, Guedes Barbosa LS, D’-Cruz D, Furie R, Maksimowicz-McKinnon K, Oates J, Santiago MB, Saxena A, Sheikh S, Bass DL, 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;74:112–23.
  • Sheikh SZ, Scheinberg MA, Wei J-C, Tegzova D, Stohl W, de Toledo RA, Mucenic T, Banfi MRA, Maksimowicz-McKinnon K, Abud-Mendoza C, et al. Mortality and adverse events of special interest with intravenous belimumab for adults with active, autoantibody-positive systemic lupus erythematosus (BASE): a multicentre, double-blind, randomised, placebo-controlled, phase 4 trial. Lancet Rheumatol. 2021;3(2):e122–30. doi:10.1016/S2665-9913(20)30355-6.
  • Freedman BI, Langefeld CD, Andringa KK, Croker JA, Williams AH, Garner NE, Birmingham DJ, Hebert LA, Hicks PJ, Segal MS, et al. End-stage renal disease in African Americans with lupus nephritis is associated with APOL1. Arthritis Rheumatol. 2014;66(2):390–96. doi:10.1002/art.38220.
  • Lea JP. Lupus nephritis in African Americans. Am J Med Sci. 2002;323(2):85–89. doi:10.1097/00000441-200202000-00005.
  • De Scheerder M-A, Boey O, Mahieu E, Vanuytsel J, Bogaert A-M. Case report: successful treatment of membranous lupus nephritis with belimumab in an African female immigrant. Clin Rheumatol. 2016;35(6):1649–53. doi:10.1007/s10067-015-3153-1.
  • Fontana F, Alfano G, Leonelli M, Cerami C, Ligabue G, Spinella A, Citriniti G, Manzini CU, Ferri C, Cappelli G. Efficacy of Belimumab for active lupus nephritis in a young Hispanic woman intolerant to standard treatment: a case report. BMC Nephrol. 2018;19(1):276. doi:10.1186/s12882-018-1066-3.
  • Binda V, Trezzi B, Del Papa N, Beretta L, Frontini G, Porata G, Fabbrini P, Pozzi MR, Messa P, Sinico RA, et al. Belimumab may decrease flare rate and allow glucocorticoid withdrawal in lupus nephritis (including dialysis and transplanted patient). J Nephrol. 2020;33(5):1019–25. doi:10.1007/s40620-020-00706-3.
  • Rovin BH, Furie R, Teng YKO, Contreras G, Malvar A, Yu X, Ji B, Green Y, Gonzalez-Rivera T, Bass D, et al. A secondary analysis of the belimumab international study in lupus nephritis trial examined effects of belimumab on kidney outcomes and preservation of kidney function in patients with lupus nephritis. Kidney Int. 2022;101(2):403–13. doi:10.1016/j.kint.2021.08.027.
  • Hui-Yuen JS, Reddy A, Taylor J, Li X, Eichenfield AH, Bermudez LM, Starr AJ, Imundo LF, Buyon J, Furie RA, et al. Safety and efficacy of belimumab to treat systemic lupus erythematosus in academic clinical practices. J Rheumatol. 2015;42(12):2288–95. doi:10.3899/jrheum.150470.
  • Parodis I, Vital EM, Hassan S-U, Jönsen A, Bengtsson AA, Eriksson P, Leonard D, Gunnarsson I, Rönnblom L, Sjöwall C. De Novo lupus nephritis during treatment with belimumab. Rheumatology (Oxford). 2021;60(9):4348–54. doi:10.1093/rheumatology/keaa796.
  • Sjöwall C, Cöster L. Belimumab may not prevent lupus nephritis in serologically active patients with ongoing non-renal disease activity. Scand J Rheumatol. 2014;43(5):428–30. doi:10.3109/03009742.2014.887769.
  • Staveri C, Karokis D, Liossis S-N. New onset of lupus nephritis in two patients with SLE shortly after initiation of treatment with belimumab. Semin Arthritis Rheum. 2017;46(6):788–90. doi:10.1016/j.semarthrit.2016.09.006.
  • Anjo C, Mascaró J-M, Espinosa G, Cervera R. Effectiveness and safety of belimumab in patients with systemic lupus erythematosus in a real-world setting. Scand J Rheumatol. 2019;48(6):469–73. doi:10.1080/03009742.2019.1603324.
  • Riancho-Zarrabeitia L, Villa Blanco I, Santos-Gómez M, Aurrecoechea E. Belimumab in systemic lupus erythematosus: experience in clinical practice settings in a regional hospital. Reumatol Clin (Engl Ed). 2020;16:188–89. doi:10.1016/j.reuma.2018.02.004.
  • Hassan SU, Md Yusof MY, Emery P, Dass S, Vital EM. Biologic sequencing in systemic lupus erythematosus: after secondary non-response to rituximab, switching to humanised anti-CD20 agent is more effective than belimumab. Front Med (Lausanne). 2020;7:498. doi:10.3389/fmed.2020.00498.
  • Condon MB, Ashby D, Pepper RJ, Cook HT, Levy JB, Griffith M, Cairns TD, Lightstone L. 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):1280–86. doi:10.1136/annrheumdis-2012-202844.
  • Kraaij T, Huizinga TWJ, Rabelink TJ, Teng YKO. Belimumab after rituximab as maintenance therapy in lupus nephritis. Rheumatology (Oxford). 2014;53(11):2122–24. doi:10.1093/rheumatology/keu369.
  • Gualtierotti R, Borghi MO, Gerosa M, Schioppo T, Larghi P, Geginat J, Meroni PL. Successful sequential therapy with rituximab and belimumab in patients with active systemic lupus erythematosus: a case series. Clin Exp Rheumatol. 2018;36:643–47.
  • Gonzalez-Echavarri C, Ugarte A, Ruiz-Irastorza G. Rituximab-Refractory lupus nephritis successfully treated with belimumab. Clin Exp Rheumatol. 2016;34:355–56.
  • Simonetta F, Allali D, Roux-Lombard P, Chizzolini C. Successful treatment of refractory lupus nephritis by the sequential use of rituximab and belimumab. Joint Bone Spine. 2017;84(2):235–36. doi:10.1016/j.jbspin.2016.01.008.
  • Kraaij T, Kamerling SWA, de Rooij ENM, van Daele PLA, Bredewold OW, Bakker JA, Bajema IM, Scherer HU, Toes REM, Huizinga TJW, et al. The NET-effect of combining rituximab with belimumab in severe systemic lupus erythematosus. J Autoimmun. 2018;91:45–54. doi:10.1016/j.jaut.2018.03.003.
  • van Dam LS, Osmani Z, Kamerling SWA, Kraaij T, Bakker JA, Scherer HU, Rabelink TJ, Voll RE, Alexander T, Isenberg DA, et al. A reverse translational study on the effect of rituximab, rituximab plus belimumab, or bortezomib on the humoral autoimmune response in SLE. Rheumatology (Oxford). 2020;59(10):2734–45. doi:10.1093/rheumatology/kez623.
  • Shipa M, Embleton-Thirsk A, Parvaz M, Santos LR, Muller P, Chowdhury K, Isenberg DA, Doré CJ, Gordon C, Ehrenstein MR, et al. Effectiveness of belimumab after rituximab in systemic lupus erythematosus. Annals of Internal Medicine [Internet]. 2021 [accessed 2021 Nov 30]. https://www.acpjournals.org/doi/abs/10.7326/M21-2078.
  • Atisha-Fregoso Y, Malkiel S, Harris KM, Byron M, Ding L, Kanaparthi S, Barry WT, Gao W, Ryker K, Tosta P, et al. Phase II randomized trial of rituximab plus cyclophosphamide followed by belimumab for the treatment of lupus nephritis. Arthritis Rheumatol. 2021;73(1):121–31. doi:10.1002/art.41466.
  • Aranow C, Allart C, Amoura Z, Bruce IN, Cagnoli P, Furie R, Tak PP, Urowitz M, van Vollenhoven R, Clark KL, et al. Efficacy and safety of Subcutaneous Belimumab (BEL) and Rituximab (RTX) sequential therapy in patients with systemic lupus erythematosus: the Phase 3, randomized, placebo-controlled BLISS-BELIEVE study [Internet]. ACR Meeting Abstracts; 2021 [accessed 2021 Dec 30]. https://acrabstracts.org/abstract/efficacy-and-safety-of-subcutaneous-belimumab-bel-and-rituximab-rtx-sequential-therapy-in-patients-with-systemic-lupus-erythematosus-the-phase-3-randomized-placebo-controlled-bliss-believe-stud/.
  • Petricca L, Gigante MR, Paglionico A, Costanzi S, Vischini G, Di Mario C, Varriano V, Tanti G, Tolusso B, Alivernini S, et al. Rituximab followed by belimumab controls severe lupus nephritis and bullous pemphigoid in systemic lupus erythematosus refractory to several combination therapies. Front Med (Lausanne). 2020;7:553075. doi:10.3389/fmed.2020.553075.
  • Kraaij T, Arends EJ, van Dam LS, Kamerling SWA, van Daele PLA, Bredewold OW, Ray A, Bakker JA, Scherer HU, Huizinga TJW, et al. Long-Term effects of combined B-cell immunomodulation with rituximab and belimumab in severe, refractory systemic lupus erythematosus: 2-year results. Nephrol Dial Transplant. 2021;36(8):1474–83. doi:10.1093/ndt/gfaa117.
  • Tada S, Yasui T, Nakatsuji Y, Okuno T, Koda T, Mochizuki H, Sakoda S, Kikutani H. BAFF controls neural cell survival through BAFF receptor. Plos One. 2013;8:e70924. doi:10.1371/journal.pone.0070924.
  • Xie W, Huang H, Zhan S, Zhang Z. Risk of psychiatric disorders and all-cause mortality with belimumab therapy in patients with systemic lupus erythematosus: a meta-analysis of randomised controlled trials. Lupus Sci Med. 2021;8(1):e000534. doi:10.1136/lupus-2021-000534.
  • Morand EF, Furie RA, Bruce IN, Vital EM, Dall’-Era M, Maho E, Pineda L, Tummala R. Efficacy of anifrolumab across organ domains in patients with moderate-to-severe systemic lupus erythematosus: a post-hoc analysis of pooled data from the TULIP-1 and TULIP-2 trials. Lancet Rheumatol. 2022;4(4):e282–92. doi:10.1016/S2665-9913(21)00317-9.
  • Mejia-Vilet JM, Malvar A, Arazi A, Rovin BH. The lupus nephritis management renaissance. Kidney Int. 2022;101(2):242–55. doi:10.1016/j.kint.2021.09.012.