Association of a multibiomarker disease activity score at multiple time-points with radiographic progression in rheumatoid arthritis: results from the SWEFOT trial

Karen Hambardzumyan, Rebecca J Bolce, Saedis Saevarsdottir, Kristina Forslind, Johan K Wallman, Scott E Cruickshank, Eric H Sasso, David Chernoff, Ronald F van Vollenhoven, Karen Hambardzumyan, Rebecca J Bolce, Saedis Saevarsdottir, Kristina Forslind, Johan K Wallman, Scott E Cruickshank, Eric H Sasso, David Chernoff, Ronald F van Vollenhoven

Abstract

Objectives: In rheumatoid arthritis (RA), predictive biomarkers for subsequent radiographic progression (RP) could improve therapeutic choices for individual patients. We previously showed that the multibiomarker disease activity (MBDA) score in patients with newly diagnosed RA identified patients at risk for RP. We evaluated the MBDA score at multiple time-points as a predictor of RP during 2 years of follow-up.

Methods: A subset of patients with RA (N=220) from the Swedish Farmacotherapy (SWEFOT) trial were analysed for MBDA score, disease activity score of 28 joints (DAS28), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at baseline (BL), month 3 and year 1, for predicting RP based on modified Sharp/van der Heijde scores at BL, year 1 and year 2.

Results: Patients with persistently low MBDA (<30) scores or those with a decrease from moderate (30-44) to low MBDA scores, did not develop RP during 2 years of follow-up. The highest risk for RP during 2 years of follow-up (42%) was observed among patients with persistently high (>44) MBDA scores. Among methotrexate non-responders with a high MBDA score at BL or month 3, significantly more of those who received triple therapy had RP at year 2 compared with those who received antitumour necrosis factor therapy.

Conclusions: Measuring the MBDA score both before and during treatment in RA was useful for the assessment of individual patient risk for RP during 2 years of follow-up. In comparison with low CRP, ESR or DAS28, a low MBDA score at any time-point was associated with numerically lower proportions of RP.

Trial registration number: NCT00764725.

Keywords: Anti-TNF; Cytokines; Disease Activity; Patient perspective; Rheumatoid Arthritis.

Figures

Figure 1
Figure 1
Distribution of disease activity measures among radiographic progressors (Δ Sharp/van der Heijde score (ΔSHS) >5) and non-progressors (ΔSHS≤5). Multibiomarker disease activity (MBDA) score, C reactive protein (CRP), erythrocyte sedimentation rate (ESR), disease activity score of 28 joints (DAS28), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at baseline among patients with radiographic progression (grey boxes) and without progression (white boxes) from baseline to year 1.
Figure 2
Figure 2
Proportion of radiographic progressors in patients with rheumatoid arthritis during 2 years follow-up according to categories of multibiomarker disease activity (MBDA) score, C reactive protein (CRP), erythrocyte sedimentation rate (ESR) and disease activity score of 28 joints (DAS28) at multiple time-points. The proportion of radiographic progression (RP) (A) at year 2 in patients whose 3-month categories of MBDA score are cross classified versus CRP, ESR and DAS28 at month 3 and (B) from year 1 to 2 in patients whose 1 year categories of MBDA score are cross-classified versus categories of CRP, ESR or DAS28 at year 1.
Figure 3
Figure 3
Association of radiographic progression with change in disease activity categories according to the MBDA score, CRP and ESR. Change in categories according to MBDA score, CRP or ESR (A) from BL to month 3 and radiographic progression from BL to year 1, and (B) from BL to year 1 and radiographic progression from year 1 to 2. BL, baseline; CRP, C reactive protein; ESR, erythrocyte sedimentation rate; MBDA, multibiomarker disease activity; SHS, Sharp/van der Heijde score.
Figure 4
Figure 4
Radiographic progression among three therapy groups (triple therapy group, anti-TNF treatment group and MTX responders) stratified by MBDA categories at multiple time-points. Proportion of patients with radiographic progression defined as (A) ΔSHS>5 and (B) ΔSHS>3. Left and middle bar graphs represent proportion of patients with 2-year radiographic progression stratified by the MBDA score at BL and month 3, respectively. Right bar graph shows radiographic progression from year 1 to 2 among patients stratified by the MBDA score at year 1. BL, baseline; MBDA, multibiomarker disease activity; MTX, methotrexate; NS, not significant; SHS, Sharp/van der Heijde score; TNF, tumour necrosis factor.

References

    1. van Nies JAB, Krabben A, Schoones JW et al. . What is the evidence for the presence of a therapeutic window of opportunity in rheumatoid arthritis? A systematic literature review. Ann Rheum Dis 2014;73:861–70. 10.1136/annrheumdis-2012-203130
    1. Escudero-Vilaplana V, Ramirez-Herraiz E, Trovato-Lopez N et al. . Influence on effectiveness of early treatment with anti-TNF therapy in rheumatoid arthritis. J Pharm Pharm Sci 2012;15:355–60.
    1. Molenaar ET, Voskuyl AE, Dinant HJ et al. . Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission. Arthritis Rheum 2004;50:36–42. 10.1002/art.11481
    1. Klarenbeek NB, Koevoets R, van der Heijde DM et al. . Association with joint damage and physical functioning of nine composite indices and the 2011 ACR/EULAR remission criteria in rheumatoid arthritis. Ann Rheum Dis 2011;70:1815–21. 10.1136/ard.2010.149260
    1. Landewé R, Geusens P, Boers M et al. . Markers for type II collagen breakdown predict the effect of disease-modifying treatment on long-term radiographic progression in patients with rheumatoid arthritis. Arthritis Rheum 2004;50:1390–9. 10.1002/art.20222
    1. Lillegraven S, Prince FH, Shadick NA et al. . Remission and radiographic outcome in rheumatoid arthritis: application of the 2011 ACR/EULAR remission criteria in an observational cohort. Ann Rheum Dis 2012;71:681–6. 10.1136/ard.2011.154625
    1. Rezaei H, Saevarsdottir S, Forslind K et al. . In early rheumatoid arthritis, patients with a good initial response to methotrexate have excellent 2-year clinical outcomes, but radiological progression is not fully prevented: data from the methotrexate responders population in the SWEFOT trial. Ann Rheum Dis 2012;71:186–91. 10.1136/annrheumdis-2011-200038
    1. Avouac J, Gossec L, Dougados M. Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review. Ann Rheum Dis 2006;65:845–51. 10.1136/ard.2006.051391
    1. Forslind K, Ahlmén M, Eberhardt K et al. . Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP). Ann Rheum Dis 2004;63:1090–5. 10.1136/ard.2003.014233
    1. Garnero P, Landewé R, Boers M et al. . Association of baseline levels of markers of bone and cartilage degradation with long-term progression of joint damage in patients with early rheumatoid arthritis—the COBRA Study. Arthritis Rheum 2002;46: 2847–56. 10.1002/art.10616
    1. Goronzy JJ, Matteson EL, Fulbright JW et al. . Prognostic markers of radiographic progression in early rheumatoid arthritis. Arthritis Rheum 2004;50:43–54. 10.1002/art.11445
    1. Liao KP, Weinblatt ME, Cui J et al. . Clinical predictors of erosion-free status in rheumatoid arthritis: a prospective cohort study. Rheumatology (Oxford) 2011;50:1473–9. 10.1093/rheumatology/ker129
    1. Masdottir B, Jónsson T, Manfredsdottir V et al. . Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis. Rheumatology (Oxford) 2000;39:1202–5. 10.1093/rheumatology/39.11.1202
    1. Meyer O, Nicaise-Roland P, Santos MD et al. . Serial determination of cyclic citrullinated peptide autoantibodies predicted five-year radiological outcomes in a prospective cohort of patients with early rheumatoid arthritis. Arthritis Res Ther 2006;8:R40 10.1186/ar1896
    1. Nell VPK, Machold KP, Stamm TA et al. . Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann Rheum Dis 2005;64:1731–6. 10.1136/ard.2005.035691
    1. Quinn MA, Gough AKS, Green MJ et al. . Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthritis and predict radiological and functional outcome. Rheumatology (Oxford) 2006;45:478–80. 10.1093/rheumatology/kei203
    1. Saag KG, Cerhan JR, Kolluri S et al. . Cigarette smoking and rheumatoid arthritis severity. Ann Rheum Dis 1997;56:463–9. 10.1136/ard.56.8.463
    1. Smolen JS, Van Der Heijde DM, St Clair EW et al. . Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial. Arthritis Rheum 2006;54:702–10. 10.1002/art.21678
    1. Saevarsdottir S, Rezaei H, Geborek P et al. . Current smoking status is a strong predictor of radiographic progression in early rheumatoid arthritis: results from the SWEFOT trial. Ann Rheum Dis 2015;74:1509–14. 10.1136/annrheumdis-2013-204601
    1. Centola M, Cavet G, Shen Y et al. . Development of a multi-biomarker disease activity test for rheumatoid arthritis. PLoS ONE 2013;8:e60635 10.1371/journal.pone.0060635
    1. Curtis JR, van der Helm-van Mil AH, Knevel R et al. . Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity. Arthritis Care Res (Hoboken) 2012;64:1794–803. 10.1002/acr.21767
    1. van der Helm-van Mil AH, Knevel R, Cavet G et al. . An evaluation of molecular and clinical remission in rheumatoid arthritis by assessing radiographic progression. Rheumatology (Oxford) 2013;52:839–46. 10.1093/rheumatology/kes378
    1. van Vollenhoven RF, Ernestam S, Geborek P et al. . Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (SWEFOT trial): 1-year results of a randomised trial. Lancet 2009;374:459–66. 10.1016/S0140-6736(09)60944-2
    1. van Vollenhoven RF, Geborek P, Forslind K et al. . Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group SWEFOT trial. Lancet 2012;379:1712–20. 10.1016/S0140-6736(12)60027-0
    1. Hambardzumyan K, Bolce R, Saevarsdottir S et al. . Pretreatment multi-biomarker disease activity score and radiographic progression in early RA: results from the SWEFOT trial. Ann Rheum Dis 2015;74:1102–9. 10.1136/annrheumdis-2013-204986
    1. van Gestel AM, Prevoo ML, van ‘t Hof MA et al. . Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health organization/International League Against Rheumatism Criteria. Arthritis Rheum 1996;39:34–40. 10.1002/art.1780390105
    1. Takahashi N, Kojima T, Kaneko A et al. . Clinical efficacy of abatacept compared to adalimumab and tocilizumab in rheumatoid arthritis patients with high disease activity. Clin Rheumatol 2014;33:39–47. 10.1007/s10067-013-2392-2
    1. van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol 2000;27:261–3.
    1. Bruynesteyn K, van der Heijde D, Boers M et al. . Determination of the minimal clinically important difference in rheumatoid arthritis joint damage of the Sharp/van der Heijde and Larsen/Scott scoring methods by clinical experts and comparison with the smallest detectable difference. Arthritis Rheum 2002;46:913–20. 10.1002/art.10190
    1. Vastesaeger N, Xu S, Aletaha D et al. . A pilot risk model for the prediction of rapid radiographic progression in rheumatoid arthritis. Rheumatology (Oxford) 2009;48:1114–21. 10.1093/rheumatology/kep155
    1. Bruynesteyn K, Van Der Heijde D, Boers M et al. . Detecting radiological changes in rheumatoid arthritis that are considered important by clinical experts: influence of reading with or without known sequence. J Rheumatol 2002;29: 2306–12.
    1. Eastman PS, Manning WC, Qureshi F et al. . Characterization of a multiplex, 12-biomarker test for rheumatoid arthritis. J Pharm Biomed Anal 2012;70:415–24. 10.1016/j.jpba.2012.06.003
    1. Bakker MF, Cavet G, Jacobs JW et al. . Performance of a multi-biomarker score measuring rheumatoid arthritis disease activity in the CAMERA tight control study. Ann Rheum Dis 2012;71:1692–7. 10.1136/annrheumdis-2011-200963

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