Skip to main content
Top
Published in: Rheumatology International 2/2016

Open Access 01-02-2016 | Short Communication - Validation Studies

Interpreting the multi-biomarker disease activity score in the context of tocilizumab treatment for patients with rheumatoid arthritis

Authors: William G. Reiss, Jenny N. Devenport, Jason M. Low, George Wu, Eric H. Sasso

Published in: Rheumatology International | Issue 2/2016

Login to get access

Abstract

The multi-biomarker disease activity (MBDA) score measures 12 proteins involved in the pathophysiology of rheumatoid arthritis (RA) to assess disease activity (DA). Previous studies demonstrated correlations between MBDA and clinical DA scores with some RA therapies. In this analysis, the relationship between DA and MBDA scores and changes in MBDA component biomarkers were evaluated in tocilizumab (TCZ)-treated patients. Patients from the ACT-RAY study were included in this analysis if they had DA measures and serum collected at pre-specified time points with sufficient serum for MBDA testing at ≥1 visit. Descriptive statistics, associations between outcomes, and percentage agreement between DA categories were calculated. Seventy-eight patients were included and were similar to the ACT-RAY population. Correlations between MBDA score and DAS28-CRP were ρ = 0.50 at baseline and ρ = 0.26 at week 24. Agreement between low/moderate/high categories of MBDA score and DAS28-CRP was observed for 77.1 % of patients at baseline and 23.7 % at week 24. Mean changes from baseline to weeks 4, 12, and 24 were proportionately smaller for MBDA score than DAS28-CRP. Unlike some other MBDA biomarkers, interleukin-6 (IL-6) concentrations increased in most patients during TCZ treatment. Correlations and agreement between MBDA and DAS28-CRP or CDAI scores were lower at week 24 versus baseline. The proportionately smaller magnitude of response observed for MBDA score versus DAS28-CRP may be due to the influence of the increase in IL-6 concentrations on MBDA score. Thus, MBDA scores obtained during TCZ treatment should be interpreted cautiously and in the context of available clinical information.
Literature
1.
go back to reference Smolen JS, Beaulieu A, Rubbert-Roth A et al (2008) Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 371:987–997CrossRefPubMed Smolen JS, Beaulieu A, Rubbert-Roth A et al (2008) Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 371:987–997CrossRefPubMed
2.
go back to reference Genovese MC, McKay JD, Nasonov EL et al (2008) 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 58:2968–2980CrossRefPubMed Genovese MC, McKay JD, Nasonov EL et al (2008) 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 58:2968–2980CrossRefPubMed
3.
go back to reference Emery P, Keystone E, Tony HP et al (2008) 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 67:1516–1523PubMedCentralCrossRefPubMed Emery P, Keystone E, Tony HP et al (2008) 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 67:1516–1523PubMedCentralCrossRefPubMed
4.
go back to reference Kremer JM, Blanco R, Brzosko M et al (2011) 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 63:609–621CrossRefPubMed Kremer JM, Blanco R, Brzosko M et al (2011) 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 63:609–621CrossRefPubMed
5.
go back to reference Jones G, Sebba A, Gu J et al (2010) Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 69:88–96PubMedCentralCrossRefPubMed Jones G, Sebba A, Gu J et al (2010) Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 69:88–96PubMedCentralCrossRefPubMed
6.
go back to reference Nishimoto N, Terao K, Mima T et al (2008) Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood 112:3959–3964CrossRefPubMed Nishimoto N, Terao K, Mima T et al (2008) Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood 112:3959–3964CrossRefPubMed
7.
go back to reference Uchiyama Y, Yoshida H, Koike N et al (2008) Anti-IL-6 receptor antibody increases blood IL-6 level via the blockade of IL-6 clearance, but not via the induction of IL-6 production. Int Immunopharmacol 8:1595–1601CrossRefPubMed Uchiyama Y, Yoshida H, Koike N et al (2008) Anti-IL-6 receptor antibody increases blood IL-6 level via the blockade of IL-6 clearance, but not via the induction of IL-6 production. Int Immunopharmacol 8:1595–1601CrossRefPubMed
8.
go back to reference Yoshida Y, Sakamoto M, Yokota K et al (2011) Tocilizumab improved both clinical and laboratory manifestations except for interleukin-18 in a case of multiple drug-resistant adult-onset Still’s disease. Intern Med 50:1757–1760CrossRefPubMed Yoshida Y, Sakamoto M, Yokota K et al (2011) Tocilizumab improved both clinical and laboratory manifestations except for interleukin-18 in a case of multiple drug-resistant adult-onset Still’s disease. Intern Med 50:1757–1760CrossRefPubMed
9.
go back to reference Gabay C, Kushner I (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340:448–454CrossRefPubMed Gabay C, Kushner I (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340:448–454CrossRefPubMed
10.
go back to reference Nishimoto N, Yoshizaki K, Maeda K et al (2003) Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study. J Rheumatol 30:1426–1435PubMed Nishimoto N, Yoshizaki K, Maeda K et al (2003) Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study. J Rheumatol 30:1426–1435PubMed
11.
go back to reference Smolen JS, Landewe R, Breedveld FC et al (2010) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 69:964–975PubMedCentralCrossRefPubMed Smolen JS, Landewe R, Breedveld FC et al (2010) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 69:964–975PubMedCentralCrossRefPubMed
12.
go back to reference Singh JA, Furst DE, Bharat A et al (2012) 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 64:625–639CrossRef Singh JA, Furst DE, Bharat A et al (2012) 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 64:625–639CrossRef
13.
go back to reference Pincus T (2005) The American College of Rheumatology (ACR) core data set and derivative “patient only” indices to assess rheumatoid arthritis. Clin Exp Rheumatol 23:S109–S113PubMed Pincus T (2005) The American College of Rheumatology (ACR) core data set and derivative “patient only” indices to assess rheumatoid arthritis. Clin Exp Rheumatol 23:S109–S113PubMed
14.
go back to reference Clark GH, Fraser CG (1993) Biological variation of acute phase proteins. Ann Clin Biochem 30:373–376CrossRefPubMed Clark GH, Fraser CG (1993) Biological variation of acute phase proteins. Ann Clin Biochem 30:373–376CrossRefPubMed
16.
go back to reference Hirata S, Dirven L, Shen Y et al (2013) A multi-biomarker score measures rheumatoid arthritis disease activity in the BeSt study. Rheumatology (Oxford) 52:1202–1207CrossRef Hirata S, Dirven L, Shen Y et al (2013) A multi-biomarker score measures rheumatoid arthritis disease activity in the BeSt study. Rheumatology (Oxford) 52:1202–1207CrossRef
17.
go back to reference Bakker MF, Cavet G, Jacobs JW et al (2012) Performance of a multi-biomarker score measuring rheumatoid arthritis disease activity in the CAMERA tight control study. Ann Rheum Dis 71:1692–1697PubMedCentralCrossRefPubMed Bakker MF, Cavet G, Jacobs JW et al (2012) Performance of a multi-biomarker score measuring rheumatoid arthritis disease activity in the CAMERA tight control study. Ann Rheum Dis 71:1692–1697PubMedCentralCrossRefPubMed
18.
go back to reference Dougados M, Kissel K, Sheeran T et al (2013) Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis 72:43–50PubMedCentralCrossRefPubMed Dougados M, Kissel K, Sheeran T et al (2013) Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis 72:43–50PubMedCentralCrossRefPubMed
19.
go back to reference Eastman PS, Manning WC, Qureshi F et al (2012) Characterization of a multiplex, 12-biomarker test for rheumatoid arthritis. J Pharm Biomed Anal 70:415–424CrossRefPubMed Eastman PS, Manning WC, Qureshi F et al (2012) Characterization of a multiplex, 12-biomarker test for rheumatoid arthritis. J Pharm Biomed Anal 70:415–424CrossRefPubMed
20.
go back to reference Curtis JR, van der Helm-van Mil AH, Knevel R et al (2012) Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity. Arthritis Care Res (Hoboken) 64:1794–1803CrossRef Curtis JR, van der Helm-van Mil AH, Knevel R et al (2012) Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity. Arthritis Care Res (Hoboken) 64:1794–1803CrossRef
21.
go back to reference Prevoo ML, van ‘t Hof MA, Kuper HH et al (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48CrossRefPubMed Prevoo ML, van ‘t Hof MA, Kuper HH et al (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48CrossRefPubMed
22.
go back to reference Aletaha D, Nell VP, Stamm T et al (2005) Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score. Arthritis Res Ther 7:R796–R806PubMedCentralCrossRefPubMed Aletaha D, Nell VP, Stamm T et al (2005) Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score. Arthritis Res Ther 7:R796–R806PubMedCentralCrossRefPubMed
23.
go back to reference Inoue E, Yamanaka H, Hara M et al (2007) Comparison of Disease Activity Score (DAS)28- erythrocyte sedimentation rate and DAS28- C-reactive protein threshold values. Ann Rheum Dis 66:407–409PubMedCentralCrossRefPubMed Inoue E, Yamanaka H, Hara M et al (2007) Comparison of Disease Activity Score (DAS)28- erythrocyte sedimentation rate and DAS28- C-reactive protein threshold values. Ann Rheum Dis 66:407–409PubMedCentralCrossRefPubMed
24.
go back to reference Aletaha D, Ward MM, Machold KP et al (2005) Remission and active disease in rheumatoid arthritis: defining criteria for disease activity states. Arthritis Rheum 52:2625–2636CrossRefPubMed Aletaha D, Ward MM, Machold KP et al (2005) Remission and active disease in rheumatoid arthritis: defining criteria for disease activity states. Arthritis Rheum 52:2625–2636CrossRefPubMed
25.
go back to reference Hanami K, Hirata S, Tasaka H et al (2013) Behavior of the multi-biomarker disease activity (Vectra DA algorithm) score and components in patients with rheumatoid arthritis treated with tocilizumab. Ann Rheum Dis 72(suppl3):391CrossRef Hanami K, Hirata S, Tasaka H et al (2013) Behavior of the multi-biomarker disease activity (Vectra DA algorithm) score and components in patients with rheumatoid arthritis treated with tocilizumab. Ann Rheum Dis 72(suppl3):391CrossRef
26.
go back to reference Shimamoto K, Ito T, Ozaki Y et al (2013) Serum interleukin 6 before and after therapy with tocilizumab is a principal biomarker in patients with rheumatoid arthritis. J Rheumatol 40:1074–1081CrossRefPubMed Shimamoto K, Ito T, Ozaki Y et al (2013) Serum interleukin 6 before and after therapy with tocilizumab is a principal biomarker in patients with rheumatoid arthritis. J Rheumatol 40:1074–1081CrossRefPubMed
Metadata
Title
Interpreting the multi-biomarker disease activity score in the context of tocilizumab treatment for patients with rheumatoid arthritis
Authors
William G. Reiss
Jenny N. Devenport
Jason M. Low
George Wu
Eric H. Sasso
Publication date
01-02-2016
Publisher
Springer Berlin Heidelberg
Published in
Rheumatology International / Issue 2/2016
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-015-3285-2

Other articles of this Issue 2/2016

Rheumatology International 2/2016 Go to the issue