Biologic therapies for systemic lupus erythematosus: where are we now?
Journal
Current opinion in rheumatology
ISSN: 1531-6963
Titre abrégé: Curr Opin Rheumatol
Pays: United States
ID NLM: 9000851
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
pubmed:
6
9
2020
medline:
1
5
2021
entrez:
5
9
2020
Statut:
ppublish
Résumé
Conventional approaches using hydroxychloroquine, corticosteroids and immunosuppressives have improved the prognosis for systemic lupus erythematosus (SLE) patients. Unfortunately, they have reached the limits of what they can achieve and patients still die prematurely and/or find their quality of life greatly impaired. Here, we discuss the problems of assessing activity in SLE, optimizing clinical trial design and more recent biologic approaches. The success of B-cell depletion using Rituximab in open clinical studies, the approval of Belimumab (blocks the B-cell activating factor BAFF) and improvements in clinical trial design, gives cause for hope. Approaches including the use of fully humanized anti-CD20 and CD19 monoclonals, blocking interferons, inhibiting Bruton's tyrosine kinase (BTK), blocking the CD40 ligand (CD40L), utilizing an analogue of the Fc[Latin Small Letter Gamma]RIIB and an IL12-23 blocker and targeting the JAK-STAT pathway have met end points in phase II and III trials. For 20 years, we hoped that the successes of the biologic therapies in rheumatoid arthritis and psoriatic arthritis would be replicated in SLE but we have been generally disappointed. However, the encouraging recent results with monoclonals that block interferon and fully humanized anti-CD20 in particular, offer the prospect of a real revolution in the treatment of SLE.
Identifiants
pubmed: 32890026
doi: 10.1097/BOR.0000000000000736
pii: 00002281-202011000-00019
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Biological Products
0
Immunosuppressive Agents
0
Rituximab
4F4X42SYQ6
belimumab
73B0K5S26A
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
597-608Références
Bernatsky S, Boivin J-F, Joseph L. Mortality in SLE. Dubois lupus erythematosus related syndromes. 2013; Amsterdam: Elsevier, 666–675.
Croca S, Rodrigues T, Isenberg DA. Assessment of a lupus nephritis cohort over a 30-year period. Rheumatology 2011; 50:1424–1430.
In: Ciurtin C, Isenberg DA. Biologics in rheumatology - new developments, clinical uses and health implications. New York: Nova Science Publishers; 2016. 197–374.
Toumi Z, Gladman DD. Current and future therapies for SLE obstacles and recommendations for the development of novel treatments. Lupus Sci Med 2017; 4:e000239.
Murphy G, Isenberg DA. New biologics for systemic lupus erythematosus. Past imperfect future tense. Nat Rev Rheum 2019; 15:403–412.
Felson DT, Anderson JJ, Boers M, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Commitee on Outcome Measures in Rheumatoid Arthritis Clinical Trials. Arthritis Rheum 1993; 36:729–740.
Griffiths B, Mosca M, Gordon C. Assessment of patients with systemic lupus erythemsatosus and the use of lupus disease activity indices. Best Pract Res Clin Rheumatol 2005; 19:685–708.
Feld J, Isenberg DA. Why and how should we measure disease activity and damage in lupus. Presse Med 2014; 43:e151–e156.
Thanou A, Chakravarty E, James JA, Merill JT. Which outcome measures in SLE clinical trials best reflect medical judgement? Epid Outcome. Lupus Sci Med 2014; 1:e000005.
Franklyn K, Lau CS, Navarra SV, et al. Asia-Pacific Lupus Collaboration. Definition and initial validation of a lupus low disease activity state (LLDAS). Ann Rheum Dis 2016; 75:1615–1621.
Furie R, Petri M, Zamani O. BLISS-76 Study Group. A phase III randomized placebo-controlled study of Belimumab, a monoclonal antibody that inhibits B-lymphocyte stimulation, in patients with systemic lupus erythematosus. Arthritis Rheum 2011; 63:3918–3930.
Navarra SV, Guzman RM, Gallacher AE, et al. BLISS-52 Study Group. Efficacy and safety of Belimumab in patients with active systemic lupus erythematosus: a randomized placebo-controlled phase III trial. Lancet 2011; 377:721–731.
Zhang F, Bae SC, Bass D, et al. 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; 77:355–363.
Furie R, Rovin BH, Houssiau F, et al. OP0164 BLISS-LN A randomized placebo-controlled phase III trial of intravenous belimumab in patients with active lupus nephritis. Ann Rheum Dis 2020; 79:103.
Collins CE, Dall’Era M, Kan H, et al. 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:e000118.
Iaccarino L, Andreoli L, Bocci EB, et al. Clinical predictors of response and discontinuation of Belimumab in patients with systemic lupus erythematosus in real life setting. Results of a large, multicentric, nationwide study. J Autoimmun 2018; 86:1–8.
Stohl W, Schwarting A, Okada M, et al. Efficacy and safety of subcutaneous Belimumab in systemic lupus erythematosus. Arthritis Rheumatol 2017; 69:1016–1027.
Isenberg DA, Petri M, Kalunian K, et al. Efficacy and safety of subcutaneous Tabalumab in patients with systemic lupus erythematosus: results from ILLUMINATE-1, a 52-week phase III, multicentre randomized, double-blind controlled trial. Ann Rheum Dis 2016; 75:323–331.
Merrill JT, van Vollenhoven RF, Buyon JP, et al. Efficacy and safety of sub-cutaneous Tabalumab, a monoclonal antibody to B-cell activating factor, in patients with systemic lupus erythematosus: results from ILLUMINATE-2, a 52-week, phase III, multicentre, randomized, double-blind controlled study. Ann Rheum Dis 2016; 75:332–340.
Furie RA, Leon G, Thomas M, et al. A phase 2 randomised, placebo -controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study. Ann Rheum Dis 2015; 74:1667–1675.
Merrill JT, Shanahan W, Scheinberg M, et al. Phase III trial results with blisibimod, a selective inhibitor of B cell activating factor in subjects with systemic lupus erythematosus (SLE) results for a random, double blind placebo controlled study. Ann Rheum Dis 2018; 77:883–889.
Isenberg DA, Gordon C, Licu D, et al. Efficacy and safety of Atacicept for prevention of flares in patients with moderate-to-severe systemic lupus erythematosus [SLE]: 52 week data [APRIL-SLE randomized trial]. Ann Rheum Dis 2015; 74:2006–2015.
Merrill JT, Wallace DJ, Vazquez-Mateo C, et al. ADDRESS II Investigators. Safety profile in SLE patients treated with Atacicept in a phase IIb study [ADDRESS II] and its extension study. Arthritis Rheum 2017; 70:266–276.
Gordon C, Wofsy D, Wax S, et al. Post Hoc analysis of the phase II/II APRIL-SLE study. Arthritis Rheum 2017; 69:122–130.
Carter C, Isenberg DA, Ehrenstein MR. Elevated serum BAFF levels are associated with rising double stranded DNA antibody levels and disease flare following B cell depletion therapy in systemic lupus erythematosus. Arthritis Rheum 2013; 65:2672–2726.
Edwards JC, Cambridge G. Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytes. Rheumatol 2001; 40:205–211.
Leandro MJ, Edwards JC, Cambridge G, et al. An open study of B lymphocyte depletion in systemic lupus erythematosus. Arthritis Rheum 2002; 46:2673–2677.
Terrier B, Amours Z, Ravaud P, et al. Club Rhumatismes et Inflammation. Safety and efficacy of rituximabin systemic lupus erythematosus. Arthritis Rheum 2010; 62:2458–2466.
Witt M, Grunkle M, Proft F, et al. German Registry of Autoimmune Diseases (GRAID) Investigators. Clinical outcomes and safety of rituximab treatment for patients with systemic lupus erythematosus(SLE)- results from a nationwide cohort in Germany (GRAID). Lupus 2013; 22:1142–1149.
Freita S, Moto Ruiz M, Costa Carneiro A, Isanberg DA. Why do some patients with systemic lupus erythematosus fail to respond to B cell depletion using rituximab. Clin Exp Rheum 2020; 38:262–266.
McCarthy E, Suton E, Nesbitt S, et al. British Isles Lupus Assessment Group Biologics Register. Short-term efficacy and safety of rituximab therapy in refractory systemic lupus erythematosus: results from the British Isles Lupus Assessment Group Biologics Registry. Rheumotology (Oxford) 2018; 57:470–479.
Merrill JT, Newelt CM, Wallace DJ, et al. Efficacy and safety of rituximab in moderately -to-severe active systemic lupus erythematosus: the randomized, double blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum 2010; 62:222–233.
Rovin BH, Furie R, Latinis K, et al. LUNAR Investigator Group. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment With Rituximab Study. Arthritis Rheum 2012; 64:1215–1226.
Ramos L, Isenberg DA. Rituximab: the Lupus journey. Curr Treat Optn in Rheum 2015; 1:30–41.
Hahn BH, McMahon MA, Wilkinson A, et al. American College of Rheumatology. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res 2012; 64:797–808.
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; 79:713–723.
Looney RJ, Srinivasan R, Calabrese LH. The effects of rituximab on immunocompetency in patients with autoimmune disease. Arthritis Rheum 2008; 58:5–14.
Hennessey A, Lukawska J, Cambridge G, et al. Adverse infusion reactions to rituximab in systemic lupus erythematosus- a retrospective analysis. BMC Rheumatology 2019; 3:32.
Du FH, Mils EA, Mao-Draayer Y. Next generation anti CD-20monoclonal antibodies in autoimmune disease treatment. Auto Immun Highlights 2017; 8:12.
Montillo M, O’Brien S, Tedeschi A, et al. Autoimmune haemolytic anaemia and immune mediated thrombocytopenia in the phase III RESONATETM study of Ibrutinib Vs Ofatumumab in relapsed/refractory chronic lymphocytic leukaemia, including a case report. Blood 2014; 124:5654.
Masoud S, McAdoo SP, Bedi R, et al. Ofatumumab for B cell depletion in patients with systemic lupus erythematosus who are allergic to rituximab. Rheumatology (Oxford) 2018; 57:1156–1161.
Haorhaus M, Svenungsson E, Gunnarsson I. Ofatumumab treatment in lupus nephritis patients. Clin Kidney J 2015; 9:552–555.
Reddy V, Klein C, Isenberg DA, et al. Obinutuzumab induces superior B-cell cytotoxicity to Rituximab in rheumatoid arthritis and systemic lupus erythematosus patient samples. Rheumatology (Oxford) 2017; 56:1227–1237.
Dall’Era M, Aranow C, Byron M, et al. Phase 2 trial of induction therapy with anti-CD20 (Rituximab) followed by maintenance therapy with anti-BAFF (Belimumab) in patients with active lupus nephritis. Am Coll Rheumatol 2018; Abstract 1870.
Kraaij T, Kamerling SWA, de Rooij ENM, et al. Synergistic B cell immune-modulation with Rituximab and belimumab combination treatment in severe, refractory lupus. EULAR 2018; Abstract PS7: 129.
Merrill JT, June J, Koumpouras F, et al. Top line results of a phase 2, double-blind randomised, placebo-controlled study of a reversible B-cell inhibitor Xm ab® 5871 in systemic lupus erythematous. Am Coll Rheumatol Cong 2018; Late Breaking Abstract NL19.
Lopez-Herrera G, Vargas-Hernandez A, Gonzalez-Serrano ME, et al. Bruton's tyrosine kinase – an integral protein of B-cell development that also has an essential role in the innate immune system. J Leukol Biol 2014; 95:243–250.
Rankin AL, Seth N, Keegan S, et al. Selective inhibition of BTK prevents murine lupus and antibody mediated glomerulonephritis. J Immunol 2014; 95:243–250.
Hutcheson J, Vanarsa K, Bashmakov A, et al. Modulating proximal cell signalling by targeting BTK ameliorates humoral autoimmunity and end organ disease in murine lupus. Arthritis Ther Res 2012; 14:R243.
Isenberg DA, Furie R, Jones N, et al. Efficacy, Safety and pharmacodynamic effects of the Bruton's tyrosine kinase inhibitor, Fenebrutinib (GDC-0853) in moderate to severe lupus erythematosus: results of a phase 2 randomized controlled trial. Arthritis Rheumatol 2019; 71: (Suppl 10): (Abstract).
Chyuan I-T, Tzend H, Chen J. Signaling pathways of type I and type III Interferons and targeted therapies in systemic lupus erytematosus. Cells 2019; 8:963.
Bennett L, Palucka AK, Arce E, et al. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med 2003; 197:711–723.
Araujo-Fernandez S, Ahijon-Lana M, Isenberg D. Drug induced lupus: including antitumour necrosis factor and interferon induced. Lupus 2014; 23:545–553.
Kalunian KC, Merrill JT, Werth VP, et al. Maciuca RA phase II study of the efficacy and safety of Rontalizumab (rhuMAb Interferon-ɑ) in patients with systemic lupus erythematosus (ROSE). Ann Rheum Dis 2016; 75:196–202.
Khamastha M, Merrill JT, Werth VP, et al. CD1067 study investigators. Sifalimumab, an antiinterferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomized, double-blind placebo controlled study. Ann Rheum Dis 2016; 75:1909–1916.
Furie R, Morand E, Bruce I, et al. Type I Interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomized, controlled phase 3 trial. Lancet 2019; 1:E2008–E2019.
Morand E, Furie R, Tanaka Y, et al. TULIP-2 Trial Investigators. Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med 2020; 382:211–221.
Lauwerys BR, Hachulla E, Spertini F, et al. Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon ɑ-kinoid. Arthritis Rheum 2013; 65:447–456.
Higuchi T, Aiba Y, Nomura T, et al. Cuting edge: ectopic expression of CD40L on B cells induces lupus-like autoimmune disease. J Immunol 2002; 168:9–12.
Early G, Zhao W, Burns C. Anti-CD40L antibody treatment prevents the development of lupus-like nephritis in a subset of NZB-NZW mice. J Immunol 1996; 157:3159–3164.
Boumpas DT, Furie R, Manzi S, et al. BG9588 Lupus Nephritis Trial. A short course of BG9588 improves serological activity and decreases hematuria in patients with proliferative lupus GN. Arth Rheum 2003; 48:719–727.
Huang W, Sinha J, Newman J, et al. the effect of anti-CD40 ligand antibody on B cells in human systemic lupus erythematosus. Arthritis rheum 2002; 46:1554–1562.
Kalunian KC, Davis JC, Merrill JT, et al. IDEC-131 Lupus Study Group. Treatment of SLE by inhibition of T cell costimulation with anti-CD154: a randomized, double-blind, placebo-controlled trial. Arth Rheum 2002; 46:3251–3258.
Law C, Grewal I. Therapeutic interventions targeting CD40L (CD154) and CD40: the opportunities and challenges. Adv Exp med Biol 2009; 647:8–36.
Robles-Carrillo L, Meyer T, Hatfield M, et al. Anti-CD40L immune complexes potently activate platelets in vitro and cause thrombosis in FCGR2A transgenic mice. J Immunol 2010; 185:1577–1583.
Shock A, Burkly L, Wakefield, et al. CDP7657, an anti-CD40L antibody lacking an fc domain, inhibits CD40L-dependent immune responses without thrombotic complications: an in vivo study. Arthritis Res Ther 2015; 17:234.
Chamberlain C, Colman PJ, Ranger A, et al. Repeated administration of dapirolizumab pegol in a randomised phase I study is well tolerated and accompanied by improvements in several composite measures of systemic lupus erythematosus disease activity and changes in whole blood transcriptomic profiles. Ann Rheum Dis 2017; 76:1837–1844.
Furie R, Bruce I, Dörner T, et al. FRI0195 Efficacy and safety of dapirolizumab pegol in patients with moderate to severely active systemic lupus erythematosus (SLE): a randomized, placebo-controlled study. Ann Rheum Dis 2019; 78:775–776.
Hutloff A, Buchner K, Reiter K, et al. Involvement of inducible co-stimulator in the exaggerated memory B cell and plasma cell generation in systemic lupus erythematosus. Arthritis Rheum 2004; 50:3211–3220.
Sullivan BA, Tsuji W, Kivitz A, et al. Inducible T cell co-stimulator ligand (ICOSL) blockade leads to inhibition of anti-KLH IgG responses in subjects with systemic lupus erythematosus. Lupus Sci med 2016; 3:e000146.
Li F, Smith P, Ravetch JV. Inhibitory Fcγ receptor is required for the maintenance of tolerance through distinct mechanisms. J Immunol 2014; 192:3021–3028.
Stewart R, Hammond S, Oberst M, Wilkinson R. The role of Fc gamma receptors in the activity of immunomodulatory antibodies for cancer. J Immunother Cancer 2014; 2:29.
Niedere HA, Clatworthy MR, Willocks LC, et al. Fc-gamma-RIIB, Fc-gamma- R11B and systemic lupus erythematosus. Am N Y Acad Sci 2010; 83:69–86.
Tillmans S, Kolligs C, D’Cruz DP, et al. SM101, a novel recombinant soluble human FcɣIIB receptor in the treatment of systemic lupus erythematosus: results of a double blind placebo controlled multicentre study. Arthritis Rheum 2014. 67Abst No 2833.
Monneaux F, Lozano JM, Patarroyo ME, et al. T-cell recognition and therapeutic effect of a phosphorylated synthetic peptide of the 70K nRNP protein administered in MR/lpr mice. Eur J Immunol 2003; 33:287–296.
Page N, Schall N, Strub JM, et al. The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cell. PLoS One 2009; 4:e5273.
Zimmer R, Scherbarth HR, Rillo OL, et al. Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomized, double-blind, placebo-controlled phase IIb clinical trial. Ann Rheum Dis 2013; 72:1830–1835.
Yin Q, Wu LC, Zheng L, et al. Comprehensive assessment of the association between genes on JAK-STAT pathway (IFIH1, TYK2, IL-10) and systemic lupus erythematosus: a meta-analysis. Arch Dermatol Res 2018; 310:711–728.
Furumoto Y, Smith CK, Blanco L, et al. Tofacitinib ameliorates murine lupus and its associated vascular dysfunction. Arthritis Rheumatol 2017; 69:148–160.
Wallace DJ, Furie RA, Tanaka Y, et al. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet 2018; 392:222–231.
McInnes I, Kavanaugh A, Gottlieb A, et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet 2013; 382:780–789.
Van Vollenhoven RF, Hahn B, Tsokos G, et al. Efficacy and safety of ustekinumab, an Il-12 and IL-23 inhibitor, in patients with active systemic lupus erythematosus: results of a multicentre, double-blind, phase 2, randomized controlled study. Lancet 2018; (392):1330–1339.
Albrecht J, Taylor L, Berlin JA, et al. The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index): an outcome instrument for cutaneous lupus erythematosus. J Invest Dermatol 2005; 125:889–894.