IL-6 pathway-driven investigation of response to IL-6 receptor inhibition in rheumatoid arthritis

BMJ Open

Volumn 3, Issue 8, 2013, Pages

  Wang, Jianmei ^a   Platt, Adam ^a   Upmanyu, Ruchi ^a   Germer, Søren ^b   Lei, Guiyuan ^a   Rabe, Christina ^c   Benayed, Ryma ^b   Kenwright, Andrew ^a   Hemmings, Andrew ^d   Martin, Mitchell ^b   Harari, Olivier ^a  

^a ROCHE PRODUCTS LTD   (United Kingdom)

^b HOFFMANN LA ROCHE INC   (United States)

^c ROCHE DIAGNOSTICS GMBH   (Germany)

^d GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; C REACTIVE PROTEIN; DISEASE MODIFYING ANTIRHEUMATIC DRUG; INTERLEUKIN 6; INTERLEUKIN 6 RECEPTOR; METHOTREXATE; PLACEBO; PREDNISONE; TOCILIZUMAB;

ADULT; ARTICLE; DISEASE ACTIVITY; ERYTHROCYTE SEDIMENTATION RATE; FEMALE; GENOTYPE; HEALTH ASSESSMENT QUESTIONNAIRE; HUMAN; MAJOR CLINICAL STUDY; MALE; PHASE 3 CLINICAL TRIAL; RHEUMATOID ARTHRITIS; SINGLE NUCLEOTIDE POLYMORPHISM; TREATMENT RESPONSE;

EID: 84885339903     PISSN: None     EISSN: 20446055     Source Type: Journal    
DOI: 10.1136/bmjopen-2013-003199     Document Type: Article

References (32)

1. Cronstein BN. Interleukin-6-a key mediator of systemic and local symptoms in rheumatoid arthritis. Bull NYU Hosp Joint Dis 2007;65: S11-15.
2. Wrighting DM, Andrews NC Interleukin-6 induces hepcidin expression through STAT3. Blood 2006;108:3204-9.
3. Smolen JS, Beaulieu A, Rubbert-Roth A, et al Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 2008;371:987-97. (Pubitemid 351392039)
4. Emery P, Keystone E, Tony H.P., et al IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 2008;67:1516-23.
5. Genovese MC, McKay JD, Nasonov E.L., et al Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum 2008;58:2968-80.
6. Jones G, Sebba A, Gu J., et al Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 2010;69:88-96.
7. Kremer JM, Blanco R, Brzosko S., et al Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structural joint damage at one year. Arthritis Rheum 2011;63:609-21.
8. Nishimoto N, Yoshizaki K, Miyasaka N., et al Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 2004;50:1761-9. (Pubitemid 38725087)
9. Madhok R, Crilly A, Watson J., et al Serum interleukin 6 levels in rheumatoid arthritis: correlations with clinical and laboratory indices of disease activity. Ann Rheum Dis 1993;52:232-4. (Pubitemid 23094315)
10. Robak T, Gladalska A, Stepien H., et al Serum levels of interleukin-6 type cytokines and soluble interleukin-6 receptor in patients with rheumatoid arthritis. Mediators Inflamm 1998;7:347-53. (Pubitemid 28552768)
11. Galicia JC, Tai H, Komatsu Y., et al Polymorphisms in the IL-6 receptor (IL-6R) gene: strong evidence that serum levels of soluble IL-6R are genetically influenced. Genes Immun 2004;5:513-16. (Pubitemid 39263887)
12. Marinou I, Walters K, Winfield J., et al A gain of function polymorphism in the interleukin 6 receptor influences RA susceptibility. Ann Rheum Dis 2010;69:1191-4.
13. Fishman D, Faulds G, Jeffery R., et al The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 1998;102:1369-76. (Pubitemid 28467565)
14. Hingorani AD, Casas JP The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet 2012;379:1214-24.
15. Sarwar N, Butterworth AS, Freitag D.F., et al Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies. Lancet 2012;379:1205-13.
16. Ferreira MA, Matheson MC, Duffy D.L., et al Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet 2011;378:1006-14.
17. Fraunberger P, Pfeiffer M, Cremer P., et al Validation of an automated enzyme immunoassay for iInterleukin-6 for routine clinical use. Clin Chem Lab Med 1998;36:797-801. (Pubitemid 28521534)
18. Claudon A, Vergnaud P, Valverde C., et al New automated multiplex assay for bone turnover markers in osteoporosis. Clin Chem 2008;54:1554-63.
19. R&D Systems Inc. Quantikine® ELISA human IL-6 immunoassay. Minneapolis, MN: R&D Systems Inc., 2011.
20. R&D Systems Inc. Quantikine® ELISA human IL-6 sR immunoassay. Minneapolis, MN: R&D Systems Inc., 2009.
21. Irizarry RA, Bolstad BM, Collin F, et al Summaries of AffymetrixGeneChip probe level data. Nucleic Acids Res 2003;31: e15.
22. Gregersen PK, Silver J, Winchester RJ The shared epitope hypothesis: an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 1987;30:1205-13. (Pubitemid 18005792)
23. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc 1995;57:289-300.
24. Chung SJ, Kwon YJ, Park M.C., et al The correlation between increased serum concentrations of interleukin-6 family cytokines and disease activity in rheumatoid arthritis patients. Yonsei Med J 2011;52:113-20.
25. Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J 1990;265:621-36. (Pubitemid 20053863)
26. Littman BH. Tocilizumab and missed personalized medicine opportunities for patients with rheumatoid arthritis? Arthritis Rheum 2009;60:1565-6.
27. Buttgereit F, Doering G, Schaeffler A., et al Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis (CAPRA-1): a double-blind, randomised controlled trial. Lancet 2008;371:205-14.
28. Kirwan JR, Clarke L, Hunt L.P., et al Effect of novel therapeutic glucocorticoids on circadian rhythms of hormones and cytokines in rheumatoid arthritis. Ann NY Acad Sci 2010;1193:127-33.
29. Rafiq S, Frayling TM, Murray A, et al A common variant of the interleukin 6 receptor (IL-6r) gene increases IL-6r and IL-6 levels, without other inflammatory effects. Genes Immun 2007;8:552-9. (Pubitemid 350011687)
30. De Benedetti F., Pignatti P, Gerloni V., et al Differences in synovial fluid cytokine levels between juvenile and adult rheumatoid arthritis. J Rheumatol 1997;24:1403-9. (Pubitemid 27353389)
31. Frieling JT, Sauerwein RW, Wijdenes J, et al Soluble interleukin 6 receptor in biological fluids from human origin. Cytokine 1994;6:376-81. (Pubitemid 24263882)
32. Wang J, Bansal AT, Martin M, et al Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis. Pharmacogenomics J 2013;13:235-41.