Update on clinical trials in systemic lupus erythematosus

Current Opinion in Rheumatology

Volumn 28, Issue 5, 2016, Pages 477-487

  Narain, Sonali ^a   Furie, Richard ^a  

^a DONALD AND BARBARA ZUCKER SCHOOL OF MEDICINE AT HOFSTRA NORTHWELL   (United States)

Author keywords

B cells; clinical trials; interferon; systemic lupus erythematosus; T cells

Indexed keywords

ABATACEPT; ALPHA INTERFERON; ALPHA INTERFERON RECEPTOR; AMG 557; ANIFROLUMAB; ATACICEPT; BARICITINIB; BELIMUMAB; CALCINEURIN INHIBITOR; CC 220; EDRATIDE; EPRATUZUMAB; GAMMA INTERFERON; INTERLEUKIN 6; NEW DRUG; OCRELIZUMAB; PROTEASOME INHIBITOR; RUPLIZUMAB; SIFALIMUMAB; TORALIZUMAB; UNCLASSIFIED DRUG; AMG 811; AMG623 PEPTIBODY; CYCLOSPORIN; HYBRID PROTEIN; IMMUNOSUPPRESSIVE AGENT; INTERFERON; LAQUINIMOD; MONOCLONAL ANTIBODY; OBINUTUZUMAB; PEPTIDE FRAGMENT; QUINOLONE DERIVATIVE; RONTALIZUMAB; TABALUMAB; TACROLIMUS;

B LYMPHOCYTE; CELL GROWTH; CELL SURFACE; CLINICAL TRIAL (TOPIC); CONTROLLED CLINICAL TRIAL (TOPIC); DRUG INHIBITION; DRUG TARGETING; HUMAN; META ANALYSIS (TOPIC); MULTICENTER STUDY (TOPIC); PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SURVIVAL FACTOR; SYSTEMIC LUPUS ERYTHEMATOSUS; TARGET CELL; HERPES ZOSTER; IMMUNOLOGY; LUPUS ERYTHEMATOSUS, SYSTEMIC; LUPUS NEPHRITIS; MAINTENANCE CHEMOTHERAPY; PLASMA CELL; REMISSION; T LYMPHOCYTE; TREATMENT OUTCOME;

ABATACEPT; ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; B-LYMPHOCYTES; CLINICAL TRIALS AS TOPIC; CYCLOSPORINE; HERPES ZOSTER; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INTERFERON TYPE I; LUPUS ERYTHEMATOSUS, SYSTEMIC; LUPUS NEPHRITIS; MAINTENANCE CHEMOTHERAPY; PEPTIDE FRAGMENTS; PLASMA CELLS; QUINOLONES; RECOMBINANT FUSION PROTEINS; REMISSION INDUCTION; T-LYMPHOCYTES; TACROLIMUS; TREATMENT OUTCOME;

EID: 84975137574     PISSN: 10408711     EISSN: 15316963     Source Type: Journal    
DOI: 10.1097/BOR.0000000000000311     Document Type: Review

References (96)

1. Niewold TB. Advances in lupus genetics. Curr Opin Rheumatol 2015; 27:440-447.
2. Jacob N, Stohl W. Autoantibody-dependent and autoantibody-independent roles for B cells in systemic lupus erythematosus: past, present, and future. Autoimmunity 2010; 43:84-97.
3. Baker KP, Edwards BM, Main SH, et al. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum 2003; 48:3253-3265.
4. 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; 377:721-731.
5. 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; 63:3918-3930.
6. Wallace DJ, Stohl W, Furie RA, 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; 61:1168-1178.
7. Ginzler EM, Wallace DJ, Merrill JT, et al. Disease control and safety of belimumab plus standard therapy over 7 years in patients with systemic lupus erythematosus. J Rheumatol 2014; 41:300-309.
8. Struemper HMT, Gilbert J, Barton ME, et al. A randomized, open label study to evaluate the relative bioavailability of a single dose of belimumab administered subcutaneously by prefilled syringe or autoinjector. Ann Rheum Dis 2015; 74 (Suppl 2):342.
9. Stohl WSA, Okada M, Scheinberg M, et al. A randomized, double-blind, placebo-controlled, 52-week study of the efficacy and safety of belimumab administered subcutaneously plus standard care to patients with systemic lupus erythematosus (SLE). Arthritis Rheumatol 2015; 67 (Suppl 10).
10. 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.
11. Hui-Yuen JS, Reddy A, Taylor J, et al. Safety and efficacy of belimumab to treat systemic lupus erythematosus in academic clinical practices. J Rheumatol 2015; 42:2288-2295.
12. 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; 22:63-72.
13. Manzi S, Sanchez-Guerrero J, Merrill JT, 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; 71:1833-1838.
14. Dall'Era M, Chakravarty E, Wallace D, et al. Reduced B lymphocyte and immunoglobulin levels after atacicept treatment in patients with systemic lupus erythematosus: results of a multicenter, phase Ib, double-blind, placebo-controlled, dose-escalating trial. Arthritis Rheum 2007; 56:4142-4150.
15. Pena-Rossi C, Nasonov E, Stanislav M, et al. An exploratory dose-escalating study investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous atacicept in patients with systemic lupus erythematosus. Lupus 2009; 18:547-555.
16. Ginzler EM, Wax S, Rajeswaran A, et al. Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. Arthritis Res Ther 2012; 14:R33.
17. Isenberg D, 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 randomised trial). Ann Rheum Dis 2015; 74:2006-2015.
18. Stohl W, Merrill JT, Looney RJ, et al. Treatment of systemic lupus erythematosus patients with the BAFF antagonist ?peptibody? blisibimod (AMG 623/A-623): results from randomized, double-blind phase 1a and phase 1b trials. Arthritis Res Ther 2015; 17:215.
19. Furie RA, Leon G, Thomas M, et al. A phase 2, randomised, placebocontrolled 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.
20. 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, randomised, double-blind, placebo-controlled study. Ann Rheum Dis 2016; 75:323-331.
21. Merrill JT, van Vollenhoven RF, Buyon JP, et al. Efficacy and safety of subcutaneous 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, randomised, double-blind, placebo-controlled study. Ann Rheum Dis 2016; 75:332-340.
22. Dooley MARB, Radhakrishnan J, Ginzler EM, et al. The impact of tabalumab on the kidney in systemic lupus erythematosus: results from two phase 3 randomized clinical trials. Arthritis Rheumatol 2015; 67 (Suppl 10).
23. 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; 62:222-233.
24. 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 Rheum 2012; 64:1215-1226.
25. Weidenbusch M, Rommele C, Schrottle A, Anders HJ; Beyond the LUNAR trial. Efficacy of rituximab in refractory lupus nephritis. Nephrol Dial Transplant 2013; 28:106-111.
26. Iaccarino L, Bartoloni E, Carli L, et al. Efficacy and safety of off-label use of rituximab in refractory lupus: data from the Italian Multicentre Registry. Clin Exp Rheumatol 2015; 33:449-456.
27. Condon MB, Ashby D, Pepper RJ, et al. Prospective observational singlecentre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann Rheum Dis 2013; 72:1280-1286.
28. Gagez AL, Cartron G. Obinutuzumab: a new class of anti-CD20 monoclonal antibody. Curr Opin Oncol 2014; 26:484-491.
29. Reddy VKC, Isenberg DA, Cambridge G, et al. Obinutuzumab outperforms rituximab at inducing B-cell cytotoxicity in vitro through Fc-mediated effector mechanisms in rheumatoid arthritis and systemic lupus erythematosus. Arthritis Rheumatol 2015; 67 (Suppl 10).
30. Construction and characterization of a humanized, internalizing, B-cell (CD22)-specific, leukemia/lymphoma antibody, LL2. Mol Immunol 1995; 32 (17-18):1413-1427.
31. Dorner T, Kaufmann J, Wegener WA, et al. Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus. Arthritis Res Ther 2006; 8:R74.
32. RossiEA, GoldenbergDM, MichelR, et al. Trogocytosis ofmultiple B-cell surface markers by CD22 targeting with epratuzumab. Blood 2013; 122:3020-3029.
33. Wallace DJ, Gordon C, Strand V, et al. 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) 2013; 52:1313-1322.
34. Strand V, Petri M, Kalunian K, et al. Epratuzumab for patients with moderate to severe flaring SLE: health-related quality of life outcomes and corticosteroid use in the randomized controlled ALLEVIATE trials and extension study SL0006. Rheumatology (Oxford) 2014; 53:502-511.
35. Wallace DJ, Kalunian K, Petri MA, et al. 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 2014; 73:183-190.
36. Wallace DJSV, Furie R, Strand V, et al. Evaluation of treatment success in systemic lupus erythematosus clinical trials: development of the British Isles Lupus Assessment Group-based Composite Lupus Assessment Endpoint. Arthritis Rheum 2011; 63 (S10):S885.
37. Clowse MEBWD, Furie R, Petri M, et al. Efficacy and safety of epratuzumab in patients with moderate-To-severe systemic lupus erythematosus: results from two phase 3 randomized placebo-controlled trials. Arthritis Rheumatol 2015; 67 (Suppl 10).
38. 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; 74:1474-1478.
39. Mak A, Kow NY. The pathology of T cells in systemic lupus erythematosus. J Immunol Res 2014; 2014:419029.
40. Fernandez O. Oral laquinimod treatment in multiple sclerosis. Neurologia 2011; 26:111-117.
41. Jayne DAG, Chan TM, Barkay H, et al. A Randomized controlled study of laquinimod in active lupus nephritis patients in combination with standard of care. Ann Rheum Dis 2013; 72 (Suppl 3):164.
42. Sthoeger ZM, Sharabi A, Molad Y, et al. Treatment of lupus patients with a tolerogenic peptide, hCDR1 (Edratide): immunomodulation of gene expression. J Autoimmun 2009; 33:77-82.
43. Urowitz MB, Isenberg DA, Wallace DJ. Safety and efficacy of hCDR1 (Edratide) in patients with active systemic lupus erythematosus: results of phase II study. Lupus Sci Med 2015; 2:e000104.
44. Muller S, Monneaux F, Schall N, et al. Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial. Arthritis Rheum 2008; 58:3873-3883.
45. Zimmer R, Scherbarth HR, Rillo OL, et al. Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomised, double-blind, placebocontrolled phase IIb clinical trial. Ann Rheum Dis 2013; 72:1830-1835.
46. Liu J, Farmer JDJr, Lane WS, et al. Calcineurin is a commontarget of cyclophilincyclosporin A and FKBP-FK506 complexes. Cell 1991; 66:807-815.
47. Zavada J, Pesickova S, Rysava R, et al. Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study. Lupus 2010; 19:1281-1289.
48. Moroni G, Doria A, Mosca M, et al. A randomized pilot trial comparing cyclosporine and azathioprine for maintenance therapy in diffuse lupus nephritis over four years. Clin J Am Soc Nephrol 2006; 1:925-932.
49. Zavada J, Sinikka Pesickova S, Rysava R, et al. Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A. Lupus 2014; 23:69-74.
50. Hannah J, Casian A, D'Cruz D. Tacrolimus use in lupus nephritis: a systematic review and meta-Analysis. Autoimmun Rev 2016; 15:93-101.
51. Zhang X, Ji L, Yang L, et al. The effect of calcineurin inhibitors in the induction and maintenance treatment of lupus nephritis: a systematic review and metaanalysis. Int Urol Nephrol 2016; 48:731-743.
52. Liu Z, Zhang H, Liu Z, et al. Multitarget therapy for induction treatment of lupus nephritis: a randomized trial. Ann Intern Med 2015; 162:18-26.
53. Mok CC, Ying KY, Yim CW, et al. Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: a randomised controlled trial and longterm follow-up. Ann Rheum Dis 2016; 75:30-36.
54. Sullivan BTW, Chindalore VL, Geppert TD, et al. Administration of AMG 557, a human anti-B7RP-1 (ICOSL) antibody, leads to the selective inhibition of anti-KLH IgG responses in subjects with SLE: results of a phase 1 randomized, double-blind, placebo-controlled, sequential, rising, multiple-dose study. In: ACR/ARHP Annual Meeting; 2013. ; ABSTRACT NUMBER: 1743.
55. Scheipers P, Reiser H. Role of the CTLA-4 receptor in T cell activation and immunity. Physiologic function of the CTLA-4 receptor. Immunol Res 1998; 18:103-115.
56. Merrill JT, Burgos-Vargas R, Westhovens R, et al. The efficacy and safety of abatacept in patients with nonlife-Threatening manifestations of systemic lupus erythematosus: results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2010; 62:3077-3087.
57. Furie R, Nicholls K, Cheng TT, et al. Efficacy and safety of abatacept in lupus nephritis: a twelve-month, randomized, double-blind study. Arthritis Rheumatol 2014; 66:379-389.
58. Wofsy D, Hillson JL, Diamond B. Comparison of alternative primary outcome measures for use in lupus nephritis clinical trials. Arthritis Rheum 2013; 65:1586-1591.
59. Wofsy D, Hillson JL, Diamond B. Abatacept for lupus nephritis: alternative definitions of complete response support conflicting conclusions. Arthritis Rheum 2012; 64:3660-3665.
60. Group AT. Treatment of lupus nephritis with abatacept: the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study. Arthritis Rheumatol 2014; 66:3096-3104.
61. Boumpas DT, Furie R, Manzi S, et al. A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis. Arthritis Rheum 2003; 48:719-727.
62. Davis JC Jr, Totoritis MC, Rosenberg J, et al. Phase I clinical trial of a monoclonal antibody against CD40-ligand (IDEC-131) in patients with systemic lupus erythematosus. J Rheumatol 2001; 28:95-101.
63. Kalunian KC, Davis JC Jr, Merrill JT, et al., Group I-LS. Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002; 46:3251-3258.
64. Nakamura M, Tanaka Y, Satoh T, et al. Autoantibody to CD40 ligand in systemic lupus erythematosus: association with thrombocytopenia but not thromboembolism. Rheumatology (Oxford) 2006; 45:150-156.
65. Chamberlain CUM, Soranson J, Watling M, et al. Repeated administration of dapirolizumab pegol (DZP) appears safe and well tolerated in patients with systemic lupus erythematosus (SLE) and is accompanied by an improvement in disease activity: results from a phase 1 study. Arthritis Rheumatol 2015; 67 (Suppl 10).
66. Crow MK. Type I interferon in the pathogenesis of lupus. J Immunol 2014; 192:5459-5468.
67. Chiche L, Jourde-Chiche N, Whalen E, et al. Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures. Arthritis Rheumatol 2014; 66:1583-1595.
68. Chuntharapai A, Lai J, Huang X, et al. Characterization and humanization of a monoclonal antibody that neutralizes human leukocyte interferon: a candidate therapeutic for IDDM and SLE. Cytokine 2001; 15:250-260.
69. McBride JM, Jiang J, Abbas AR, et al. Safety and pharmacodynamics of rontalizumab in patients with systemic lupus erythematosus: results of a phase I, placebo-controlled, double-blind, dose-escalation study. Arthritis Rheum 2012; 64:3666-3676.
70. Kalunian KC, Merrill JT, Maciuca R, et al. A Phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-Alpha) in patients with systemic lupus erythematosus (ROSE). Ann Rheum Dis 2016; 75:196-202.
71. Mathian A, Hie M, Cohen-Aubart F, Amoura Z. Targeting interferons in systemic lupus erythematosus: current and future prospects. Drugs 2015; 75:835-846.
72. Merrill JT, Wallace DJ, Petri M, et al. Safety profile and clinical activity of sifalimumab, a fully human antiinterferon alpha monoclonal antibody, in systemic lupus erythematosus: a phase I, multicentre, double-blind randomised study. Ann Rheum Dis 2011; 70:1905-1913.
73. Petri M, Wallace DJ, Spindler A, et al. Sifalimumab, a human antiinterferonalpha monoclonal antibody, in systemic lupus erythematosus: a phase I randomized, controlled, dose-escalation study. Arthritis Rheum 2013; 65:1011-1021.
74. Khamashta M, Merrill JT, Werth VP, et al. Sifalimumab, an antiinterferon-Alpha monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study. Ann Rheum Dis 2016. [Epub ahead of print] doi:10.1136/annrheumdis-2015-208562.
75. Riggs JNB, Zhang J, Xu Y, et al. Functional and mechanistic characterization of anifrolumab, a fully human, anti-IFNAR1 monoclonal antibody for the treatment of systemic lupus erythematosus. Arthritis Rheumatol 2015; 67 (Suppl 10).
76. Morehouse CCL, Wang L, Brohawn P, et al. Target modulation of a type I interferon (IFN) gene signature with sifalimumab or anifrolumab in systemic lupus erythematosus (SLE) patients in two open label phase 2 Japanese trials. In: ACR/ARHP Annual Meeting; 2014; ABSTRACT NUMBER: 719.
77. Furie RMJ, Werth V, Khamashta M, et al. Anifrolumab, an anti-interferon alpha receptor monoclonal antibody, in moderate to severe systemic lupus erythematosus (SLE). Arthritis Rheumatol 2015; 67 (Suppl 10).
78. Zagury D, Le Buanec H, Mathian A, et al. IFNalpha kinoid vaccine-induced neutralizing antibodies prevent clinical manifestations in a lupus flare murine model. Proc Natl Acad Sci U S A 2009; 106:5294-5299.
79. Mathian A, Amoura Z, Adam E, et al. Active immunisation of human interferon alpha transgenic mice with a human interferon alpha Kinoid induces antibodies that neutralise interferon alpha in sera from patients with systemic lupus erythematosus. Ann Rheum Dis 2011; 70:1138-1143.
80. Lauwerys BR, Hachulla E, Spertini F, et al. Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon alpha-kinoid. Arthritis Rheum 2013; 65:447-456.
81. Martin DWA, Boedigheimer M, Amoura Z, et al. AMG 811 (anti-IFN-gamma) treatment leads to a reduction in the whole blood IFN-signature and serum CXCL10 in subjects with systemic lupus erythematosus: results of two phase I studies. In: ACR/ARHP Annual Meeting; 2013; ABSTRACT NUMBER: 1609.
82. Martin DAAZ, Romero-Diaz J, Chong YB, et al. A multiple dose study of AMG 811 (Anti IFN Gamma) in subjects with systemic lupus erythematosus and active nephritis. Ann Rheum Dis 2015; 74 (Suppl 2):337.
83. Sullivan BGR, Russell CB, Arnold G, et al. Molecular, cellular and histopathologic assessment of baseline characteristics of sixteen subjects with discoid lupus erythematosus prior to treatment with AMG 811 (anti-IFNg). In: ACR/ARHP Annual Meeting; 2014; ABSTRACT NUMBER: 1646.
84. Werth VP, Cohen FD, Fivenson SB, et al. A 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. In: ACR/ARHP Annual Meeting; 2013; ABSTRACT NUMBER: 1608.
85. Chun HY, Chung JW, Kim HA, et al. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol 2007; 27:461-466.
86. Illei GG, Shirota Y, Yarboro CH, et al. Tocilizumab in systemic lupus erythematosus: data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum 2010; 62:542-552.
87. Szepietowski JC, Nilganuwong S, Wozniacka A, et al. Phase I, randomized, double-blind, placebo-controlled, multiple intravenous, dose-Ascending study of sirukumab in cutaneous or systemic lupus erythematosus. Arthritis Rheum 2013; 65:2661-2671.
88. van Vollenhoven RAC, Rovin B, Wagner C, et al. A phase 2, multicenter, randomized, double-blind, placebo-controlled, proof-of-concept study to evaluate the efficacy and safety of sirukumab in patients with active lupus nephritis. Ann Rheum Dis 2014; 73 (Suppl 2):78.
89. Smolen JPS, Szombati I, Wallace D, et al. Significant clinical improvement and reduction of severe flares following administration of an IL-6 monoclonal antibody in systemic lupus erythematosus (SLE) subjects with high disease activity. Ann Rheum Dis 2015; 74 (Suppl 2):141.
90. Wallace DJPS, Spindler AJ, Eimon A, et al. Improvement of disease activity and reduction of severe flares following subcutaneous administration of an IL-6 monoclonal antibody (mAb) in subjects with active generalized systemic lupus erythematosus (SLE). ACR/ARHP Annual Meeting 2014; ABSTRACT NUMBER: L5.
91. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Ann Rheum Dis 2015; 74:333-340.
92. Tanaka Y, Emoto K, Cai Z, et al. Efficacy and safety of baricitinib in Japanese patients with active rheumatoid arthritis receiving background methotrexate therapy: a 12-week, double-blind, randomized placebo-controlled study. J Rheumatol 2016; 43:504-511.
93. Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med 2016; 374:1243-1252.
94. Papp K, Menter MA, Raman M, et al. A randomized phase 2b trial of baricitinib, an oral JAK1/JAK2 inhibitor, in patients with moderate-To-severe psoriasis. Br J Dermatol 2016; doi: 10.1111/bjd.14403. [Epub ahead of print]
95. Schafer PYY, Wu L, Kosek J, et al. The CRL4 cereblon on E3 ubiquitin ligase modulator CC-220 induces degeneration of the transcription factors Aiolos and Ikaros: immunomodulation in healthy volunteers and relevance to systemic lupus erythematosus. Ann Rheum Dis 2015; 74 (Suppl 2):113.
96. Safety and efficacy of low-dose interleukin-2 treatment in systemic lupus erythematosus. Ann Rheum Dis 2015; 74 (Suppl 2):1075.