Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity

Abstract

Objective Quantitative assessment of disease activity in rheumatoid arthritis (RA) is important for patient management, and additional objective information may aid rheumatologists in clinical decision making. We validated a recently developed multibiomarker disease activity (MBDA) test relative to clinical disease activity in diverse RA cohorts. Methods Serum samples were obtained from the Index for Rheumatoid Arthritis Measurement, Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study, and Leiden Early Arthritis Clinic cohorts. Levels of 12 biomarkers were measured and combined according to a prespecified algorithm to generate the composite MBDA score. The relationship of the MBDA score to clinical disease activity was characterized separately in seropositive and seronegative patients using Pearson's correlations and the area under the receiver operating characteristic curve (AUROC) to discriminate between patients with low and moderate/high disease activity. Associations between changes in MBDA score and clinical responses 6–12 weeks after initiation of anti–tumor necrosis factor or methotrexate treatment were evaluated by the AUROC. Results The MBDA score was significantly associated with the Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP) in both seropositive (AUROC 0.77, P < 0.001) and seronegative (AUROC 0.70, P < 0.001) patients. In subgroups based on age, sex, body mass index, and treatment, the MBDA score was associated with the DAS28‐CRP ( P < 0.05) in all seropositive and most seronegative subgroups. Changes in the MBDA score at 6–12 weeks could discriminate both American College of Rheumatology criteria for 50% improvement responses ( P = 0.03) and DAS28‐CRP improvement ( P = 0.002). Changes in the MBDA score at 2 weeks were also associated with subsequent DAS28‐CRP response ( P = 0.02). Conclusion Our findings establish the criterion and discriminant validity of a novel multibiomarker test as an objective measure of RA disease activity to aid in the management of RA in patients with this condition.

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References 49

1. 1.

   Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, et al. 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). 2012;64:625-39.

   Not in our library10.1002/acr.21641

2. 2.

   Combe B, Landewe R, Lukas C, Bolosiu HD, Breedveld F, Dougados M, et al. EULAR recommendations for the management of early arthritis: report of a Task Force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2007;66:34-45.

   Not in our library10.1136/ard.2005.044354

3. 3.

   Smolen JS, Aletaha D, Bijlsma JW, Breedveld FC, Boumpas D, Burmester G, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010;69:631-7.

   Not in our library10.1136/ard.2009.123919

4. 4.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

5. 5.

   Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005;52:3381-90.

   Not in our library10.1002/art.21405

6. 6.

   Grigor C, Capell H, Stirling A, McMahon AD, Lock P, Vallance R, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004;364:263-9.

   Not in our library10.1016/s0140-6736(04)16676-2

7. 7.

   Schoels M, Knevel R, Aletaha D, Bijlsma JW, Breedveld FC, Boumpas DT, et al. Evidence for treating rheumatoid arthritis to target: results of a systematic literature search. Ann Rheum Dis. 2010;69:638-43.

   Not in our library10.1136/ard.2009.123976

8. 8.

   Van der Heijde DM, van 't Hof MA, van Riel PL, Theunisse LA, Lubberts EW, van Leeuwen MA, et al. Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score. Ann Rheum Dis. 1990;49:916-20.

   Not in our library10.1136/ard.49.11.916

9. 9.

   Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. 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. 1995;38:44-8.

   Not in our library10.1002/art.1780380107

10. 10.

    Smolen JS, Breedveld FC, Schiff MH, Kalden JR, Emery P, Eberl G, et al. A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology (Oxford). 2003;42:244-57.

    Not in our library10.1093/rheumatology/keg072

11. 11.
    Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score · 2005

    No notice
12. 12.

    Pincus T, Yazici Y, Bergman M, Maclean R, Harrington T. A proposed continuous quality improvement approach to assessment and management of patients with rheumatoid arthritis without formal joint counts, based on quantitative Routine Assessment of Patient Index Data (RAPID) scores on a Multidimensional Health Assessment Questionnaire (MDHAQ). Best Pract Res Clin Rheumatol. 2007;21:789-804.

    Not in our library10.1016/j.berh.2007.02.009

13. 13.

    Pincus T, Swearingen CJ, Bergman M, Yazici Y. RAPID3 (Routine Assessment of Patient Index Data 3), a rheumatoid arthritis index without formal joint counts for routine care: proposed severity categories compared to Disease Activity Score and Clinical Disease Activity Index categories. J Rheumatol. 2008;35:2136-47.

    Not in our library10.3899/jrheum.080182

14. 14.

    Grunke M, Antoni CE, Kavanaugh A, Hildebrand V, Dechant C, Schett G, et al. Standardization of joint examination technique leads to a significant decrease in variability among different examiners. J Rheumatol. 2010;37:860-4.

    Not in our library10.3899/jrheum.090195

15. 15.

    Klinkhoff AV, Bellamy N, Bombardier C, Carette S, Chalmers A, Esdaile JM, et al. An experiment in reducing interobserver variability of the examination for joint tenderness. J Rheumatol. 1988;15:492-4.

    Not in our library

16. 16.

    Van der Heijde D, Landewe R, van Vollenhoven R, Fatenejad S, Klareskog L. Level of radiographic damage and radiographic progression are determinants of physical function: a longitudinal analysis of the TEMPO trial. Ann Rheum Dis. 2008;67:1267-70.

    Not in our library10.1136/ard.2007.081331

17. 17.

    Graudal N, Tarp U, Jurik AG, Galloe AM, Garred P, Milman N, et al. Inflammatory patterns in rheumatoid arthritis estimated by the number of swollen and tender joints, the erythrocyte sedimentation rate, and hemoglobin: longterm course and association to radiographic progression. J Rheumatol. 2000;27:47-57.

    Not in our library

18. 18.

    Plant MJ, Williams AL, O'Sullivan MM, Lewis PA, Coles EC, Jessop JD. Relationship between time-integrated C-reactive protein levels and radiologic progression in patients with rheumatoid arthritis. Arthritis Rheum. 2000;43:1473-7.

    Not in our library10.1002/1529-0131(200007)43:7<1473::aid-anr9>3.0.co;2-n

19. 19.

    Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448-54.

    Not in our library10.1056/nejm199902113400607

20. 20.

    Keenan RT, Swearingen CJ, Yazici Y. Erythrocyte sedimentation rate and C-reactive protein levels are poorly correlated with clinical measures of disease activity in rheumatoid arthritis, systemic lupus erythematosus and osteoarthritis patients. Clin Exp Rheumatol. 2008;26:814-9.

    Not in our library

21. 21.

    Rhodes B, Merriman ME, Harrison A, Nissen MJ, Smith M, Stamp L, et al. A genetic association study of serum acute-phase C-reactive protein levels in rheumatoid arthritis: implications for clinical interpretation. PLoS Med. 2010;7:e1000341.

    Not in our library10.1371/journal.pmed.1000341

22. 22.

    Sokka T, Pincus T. Erythrocyte sedimentation rate, C-reactive protein, or rheumatoid factor are normal at presentation in 35%-45% of patients with rheumatoid arthritis seen between 1980 and 2004: analyses from Finland and the United States. J Rheumatol. 2009;36:1387-90.

    Not in our library10.3899/jrheum.080770

23. 23.

    Cavet G, Centola M, Shen Y, Haney D, Smith D, Hesterberg L, et al. Development of a multi-biomarker test for rheumatoid arthritis (RA) disease activity [abstract]. Ann Rheum Dis. 2010;69(Suppl):148.

    Not in our library

24. 24.

    Van der Heijde DM, van 't Hof MA, van Riel PL, van Leeuwen MA, van Rijswijk MH, van de Putte LB. Validity of single variables and composite indices for measuring disease activity in rheumatoid arthritis. Ann Rheum Dis. 1992;51:177-81.

    Not in our library10.1136/ard.51.2.177

25. 25.

    Tugwell P, Bombardier C. A methodologic framework for developing and selecting endpoints in clinical trials. J Rheumatol. 1982;9:758-62.

    Not in our library

26. 26.

    Wells G, Becker JC, Teng J, Dougados M, Schiff M, Smolen J, et al. Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann Rheum Dis. 2009;68:954-60.

    Not in our library10.1136/ard.2007.084459

27. 27.

    Fleischmann RM, Curtis JR, Hamburger MH, Blumstein H, Swan K, Cavet G, et al. RA population characteristics in InFoRM, a longitudinal observational study [abstract]. Ann Rheum Dis. 2010;69(Suppl):657.

    Not in our library

28. 28.

    Iannaccone CK, Lee YC, Cui J, Frits ML, Glass RJ, Plenge RM, et al. Using genetic and clinical data to understand response to disease-modifying anti-rheumatic drug therapy: data from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study. Rheumatology (Oxford). 2010;50:40-6.

    Not in our library10.1093/rheumatology/keq263

29. 29.

    De Rooy DP, van der Linden MP, Knevel R, Huizinga TW, van der Helm-van Mil AH. Predicting arthritis outcomes: what can be learned from the Leiden Early Arthritis Clinic? Rheumatology (Oxford). 2010;50:93-100.

    Not in our library10.1093/rheumatology/keq230

30. 30.

    Parker A, Izmailova ES, Narang J, Badola S, Le T, Roubenoff R, et al. Peripheral blood expression of nuclear factor-κb-regulated genes is associated with rheumatoid arthritis disease activity and responds differentially to anti-tumor necrosis factor-α versus methotrexate. J Rheumatol. 2007;34:1817-22.

    Not in our library

31. 31.

    Todd DJ, Knowlton N, Amato M, Frank MB, Schur PH, Izmailova ES, et al. Erroneous augmentation of multiplex assay measurements in patients with rheumatoid arthritis due to heterophilic binding by serum rheumatoid factor. Arthritis Rheum. 2011;63:894-903.

    Not in our library10.1002/art.30213

32. 32.

    Eastman S, Manning B, Qureshi F, Cavet G, Haney D, Shen Y, et al. Assay development for precise measurement of disease activity serum biomarkers [abstract]. Ann Rheum Dis. 2010;69(Suppl):179.

    Not in our library

33. 33.

    Bakker MF, Bijlsma JW, Jacobs JW, Haney D, Shen Y, Hesterberg LK, et al. Performance of serum biomarkers and multivariate biomarker-based test to measure disease activity in early rheumatoid arthritis treated according to the CAMERA protocol [abstract]. Ann Rheum Dis. 2010;69(Suppl):350.

    Not in our library

34. 34.

    Inoue E, Yamanaka H, Hara M, Tomatsu T, Kamatani N. Comparison of Disease Activity Score (DAS)28-erythrocyte sedimentation rate and DAS28- C-reactive protein threshold values. Ann Rheum Dis. 2007;66:407-9.

    Not in our library10.1136/ard.2006.054205

35. 35.

    Fleiss JL, Cohen JD. The equivalence of weighted κ and the intraclass correlation coefficient as measures of reliability. Educ Psychol Meas. 1973;33:613-9.

    Not in our library

36. 36.

    Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995;38:727-35.

    Not in our library10.1002/art.1780380602

37. 37.

    Efron B. Better bootstrap confidence intervals. J Am Stat Assoc. 1987;82:171-85.

    Not in our library

38. 38.

    Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343:1586-93.

    Not in our library10.1056/nejm200011303432201

39. 39.

    Pincus T, Swearingen CJ, Bergman MJ, Colglazier CL, Kaell AT, Kunath AM, et al. RAPID3 (Routine Assessment of Patient Index Data) on an MDHAQ (Multidimensional Health Assessment Questionnaire): agreement with DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) activity categories, scored in five versus more than ninety seconds. Arthritis Care Res (Hoboken). 2010;62:181-9.

    Not in our library10.1002/acr.20066

40. 40.

    Sullivan MB, Iannaccone C, Cui J, Lu B, Batra K, Weinblatt M, et al. Evaluation of selected rheumatoid arthritis activity scores for office-based assessment. J Rheumatol. 2010;37:2466-8.

    Not in our library10.3899/jrheum.091349

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• Development of a Multi-Biomarker Disease Activity Test for Rheumatoid Arthritis · 2013
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