Gene Expression and Pharmacodynamic Changes in 1,760 Systemic Lupus Erythematosus Patients From Two Phase III Trials of BAFF Blockade With Tabalumab

Arthritis and Rheumatology

Volumn 69, Issue 3, 2017, Pages 643-654

  Hoffman, Robert W ^a   Merrill, Joan T ^b   Alarcón Riquelme, Marta M E ^c   Petri, Michelle ^d   Dow, Ernst R ^a   Nantz, Eric ^a   Nisenbaum, Laura K ^a   Schroeder, Krista M ^a   Komocsar, Wendy J ^a   Perumal, Narayanan B ^a   Linnik, Matthew D ^a   Airey, David C ^a   Liu, Yushi ^a   Rocha, Guilherme V ^a   Higgs, Richard E ^a  

^a ELI LILLY AND COMPANY   (United States)

^b OKLAHOMA MEDICAL RESEARCH FOUNDATION   (United States)

^c JUNTA DE ANDALUCÍA   (Spain)

^d JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

B CELL ACTIVATING FACTOR; DOUBLE STRANDED DNA ANTIBODY; IMMUNOGLOBULIN; INTERFERON; TABALUMAB; MONOCLONAL ANTIBODY; TNFSF13B PROTEIN, HUMAN;

ADULT; AGED; ARTICLE; CONTROLLED STUDY; DISEASE ACTIVITY; DISEASE EXACERBATION; FEMALE; GENE EXPRESSION; HUMAN; HUMAN CELL; IMMUNE RESPONSE GENE; IMMUNOGLOBULIN BLOOD LEVEL; IMMUNOGLOBULIN GENE; MAJOR CLINICAL STUDY; MALE; PHARMACODYNAMICS; PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SYSTEMIC LUPUS ERYTHEMATOSUS; ADOLESCENT; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; DOUBLE BLIND PROCEDURE; DRUG EFFECTS; GENETICS; LUPUS ERYTHEMATOSUS, SYSTEMIC; MIDDLE AGED; PHASE 3 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; VERY ELDERLY; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL; B-CELL ACTIVATING FACTOR; DOUBLE-BLIND METHOD; FEMALE; GENE EXPRESSION; HUMANS; LUPUS ERYTHEMATOSUS, SYSTEMIC; MALE; MIDDLE AGED; YOUNG ADULT;

EID: 85014102112     PISSN: 23265191     EISSN: 23265205     Source Type: Journal    
DOI: 10.1002/art.39950     Document Type: Article

References (45)

1. Lisnevskaia L, Murphy G, Isenberg D. Systemic lupus erythematosus. Lancet 2014;384:1878–88.
2. D'Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet 2007;369:587–96.
3. Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, et al. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med 1999;189:1747–56.
4. Cancro MP, D'Cruz DP, Khamashta MA. The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus. J Clin Invest 2009;119:1066–73.
5. Darce JR, Arendt BK, Wu X, Jelinek DF. Regulated expression of BAFF-binding receptors during human B cell differentiation. J Immunol 2007;179:7276–86.
6. Stohl W, Metyas S, Tan SM, Cheema GS, Oamar B, Roschke V, et al. B lymphocyte stimulator overexpression in patients with systemic lupus erythematosus: longitudinal observations. Arthritis Rheum 2003;48:3475–86.
7. Petri M, Stohl W, Chatham W, McCune WJ, Chevrier M, Ryel J, et al. Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum 2008;58:2453–9.
8. Navarra SV, Guzman RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomized, placebo-controlled, phase 3 trial. Lancet 2011;377:721–31.
9. Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzová D, 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;63:3918–30.
10. Furie RA, Leon G, Thomas M, Petri MA, Chu AD, Hislop C, et al. A phase 2, randomized, 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;74:1667–75.
11. Isenberg DA, Petri M, Kalunian K, Tanaka Y, Urowitz MB, Hoffman RW, 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;75:323–31.
12. Merrill JT, van Vollenhoven RF, Buyon JP, Furie RA, Stohl W, Morgan-Cox M, 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;75:332–40.
13. Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe systemic lupus. Proc Natl Acad Sci U S A 2003;100:2610–5.
14. Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J, Banchereau J, et al. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med 2003;197:711–23.
15. Kirou KA, Lee C, George S, Louca K, Peterson MG, Crow MK. Activation of the interferon-α pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheum 2005;52:1491–503.
16. Kennedy WP, Maciuca R, Wolslegel K, Tew W, Abbas A, Chaivorapol C, et al. Association of the interferon signature metric with serologic disease manifestations but not global activity scores in multiple cohorts of patients with SLE. Lupus Sci Med 2015;2:e000080.
17. Carpintero MF, Martinez L, Fernandez I, Romero AC, Mejia C, Zang YJ, et al. Diagnosis and risk stratification in patients with anti-RNP autoimmunity. Lupus 2015;24:1057–66.
18. Petri M, Kim MY, Kalunian KC, Grossman J, Hahn BH, Sammaritano LR, et al, for the OC-SELENA Trial. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 2005;353:2550–8.
19. Hochberg MC, for the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [letter]. Arthritis Rheum 1997;40:1725.
20. Deng Y, Tsao BP. Genetic susceptibility to systemic lupus erythematosus in the genomic era. Nat Rev Rheumatol 2010;6:683–92.
21. Guerra SG, Vyse TJ, Cunninghame Graham DS. The genetics of lupus: a functional perspective. Arthritis Res Ther 2012;14:211.
22. Irizarry RA, Bolstad BM, Collin F, Cope LM, Hobbs B, Speed TP. Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res 2003;31:e15.
23. Geiss GK, Bumgarner RE, Birditt B, Dahl T, Dowidar N, Dunaway DL, et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol 2008;26:317–25.
24. Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 2008;9:559.
25. Langfelder P, Luo R, Oldham MC, Horvath S. Is my network module preserved and reproducible? PLoS Comput Biol 2011;7:e1001057.
26. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Statistical Soc 1995;57:289–300.
27. Liu A, Qu Y, Tang L, Ting N, Tsong Y, editors. A framework of statistical methods for identification of subgroups with differential treatment effects in randomized trials. Applied statistics in biomedicine and clinical trials design: selected papers from 2013 ICSA. New York: Springer Verlag; 2015.
28. Leon AC, Heo M. Sample sizes required to detect interactions between two binary fixed-effects in a mixed-effects linear regression model. Comput Stat Data Anal 2009;53:603–8.
29. Eisenberg E, Levanon EY. Human housekeeping genes, revisited [published erratum appears in Trends Genet 2014;30:119–20]. Trends Genet 2013;29:569–74.
30. Kariuki SN, Ghodke-Puranik Y, Dorschner JM, Chrabot BS, Kelly JA, Tsao BP, et al. Genetic analysis of the pathogenic molecular sub-phenotype interferon-α identifies multiple novel loci involved in systemic lupus erythematosus. Genes Immun 2015;16:15–23.
31. Chiche L, Jourde-Chiche N, Whalen E, Presnell S, Gersuk V, Dang K, et al. Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures. Arthritis Rheumatol 2014;66:1583–95.
32. Ramos PS, Williams AH, Ziegler JT, Comeau ME, Guy RT, Lessard CJ, et al. Genetic analyses of interferon pathway–related genes reveal multiple new loci associated with systemic lupus erythematosus. Arthritis Rheum 2011;63:2049–57.
33. Bentham J, Morris DL, Cunninghame Graham DS, Pinder DL, Tombleson P, Behrens TW, et al. Genetic association analyses implicated aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus. Nat Genet 2015;47:1457–64.
34. Krueger JG, Fretzin S, Suarez-Farinas M, Haslett PA, Phipps KM, Cameron GS, et al. IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol 2012;130:145–54.e9.
35. Hofmann-Apitius M, Alarcón-Riquelme ME, Chamberlain C, McHale D. Towards the taxonomy of human disease. Nat Rev Drug Discov 2015;14:75–6.
36. Kalunian KC, Merrill JT, Maciuca R, McBride JM, Townsend MJ, Wei X, et al. A phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-α) in patients with systemic lupus erythematosus (ROSE). Ann Rheum Dis 2016;75:196–202.
37. 3 on the interferon signature in patients with systemic lupus erythematosus. Arthritis Rheumatol 2015;67:1848–57.
38. Petri M, Singh S, Tesfasyone H, Dedrick R, Fry K, Lal P, et al. Longitudinal expression of type I interferon responsive genes in systemic lupus erythematosus. Lupus 2009;18:980–9.
39. Landolt-Marticorena C, Bonventi G, Lubovich A, Ferguson C, Unnithan T, Su J, et al. Lack of association between the interferon-α signature and longitudinal changes in disease activity in systemic lupus erythematosus. Ann Rheum Dis 2009;68:1440–6.
40. Feng X, Wu H, Grossman JM, Hanvivadhanakul P, FitzGerald JD, Park GS, et al. Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus. Arthritis Rheum 2006;54:2951–62.
41. Weckerle CE, Franek BS, Kelly JA, Kumabe M, Mikolaitis RA, Green SL, et al. Network analysis of associations between serum interferon-α activity, autoantibodies, and clinical features in systemic lupus erythematosus. Arthritis Rheum 2011;63:1044–53.
42. Niewold TB, Hua J, Lehman TJ, Harley JB, Crow MK. High serum IFN-α activity is a heritable risk factor for systemic lupus erythematosus. Genes Immun 2007;8:492–502.
43. Streicher K, Morehouse CA, Groves CJ, Rajan B, Pilataxi F, Lehmann KP, et al. The plasma cell signature in autoimmune disease. Arthritis Rheumatol 2014;66:173–84.
44. Novershtern N, Subramanian A, Lawton LN, Mak RH, Haining WN, McConkey ME, et al. Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell 2011;144:296–309.
45. Banchereau R, Hong S, Cantarel B, Baldwin N, Baisch J, Edens M, et al. Personalized immunomonitoring uncovers molecular networks that stratify lupus patients. Cell 2016;165:551–65.