C H Brahe1,2,3, M Østergaard1,2,3, J S Johansen4, N Defranoux5, X Wang5, R Bolce5, E H Sasso5, L M Ørnbjerg1,3, K Hørslev-Petersen6, K Stengaard-Pedersen7, P Junker8, T Ellingsen9, P Ahlquist10, H Lindegaard8, A Linauskas11, A Schlemmer12, M Y Dam9, I Hansen13, T Lottenburger10, C Ammitzbøll7, A Jørgensen7, S B Krintel1,3, J Raun6, M L Hetland1,2,3. 1. a Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet , Glostrup , Denmark. 2. b Department of Clinical Medicine , University of Copenhagen , Copenhagen , Denmark. 3. c DANBIO Registry, Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet , Glostrup , Denmark. 4. d Department of Medicine and Oncology , Copenhagen University Hospital at Herlev , Herlev , Denmark. 5. e Crescendo Bioscience Inc ., San Francisco , CA , USA. 6. f King Christian X Hospital for Rheumatic Diseases , South Jutland Hospital , Gråsten , Denmark. 7. g Department of Rheumatology , Aarhus University Hospital, and Institute of Clinical Medicine, Aarhus University , Aarhus , Denmark. 8. h Department of Rheumatology C , Odense University Hospital , Odense , Denmark. 9. i Diagnostic Centre, Silkeborg Regional Hospital , Silkeborg , Denmark. 10. j Department of Medicine , Vejle Regional Hospital , Vejle , Denmark. 11. k Department of Rheumatology , Vendsyssel Hospital , Hjørring , Denmark. 12. l Department of Rheumatology , Aalborg University Hospital , Aalborg , Denmark. 13. m Department of Rheumatology , Viborg Regional Hospital , Viborg , Denmark.
Abstract
OBJECTIVES: Measurement of serum biomarkers at disease onset may improve prediction of disease course in patients with early rheumatoid arthritis (RA). We evaluated the multi-biomarker disease activity (MBDA) score and early changes in MBDA score for prediction of 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) remission and radiographic progression in the double-blinded OPERA trial. METHOD: Treatment-naïve RA patients (N = 180) with moderate or high DAS28 were randomized to methotrexate (MTX) + adalimumab (n = 89) or MTX + placebo (n = 91) in combination with glucocorticoid injection into swollen joints. X-rays of hands and feet were evaluated at months 0 and 12 (n = 164) by the total Sharp van der Heijde score (TSS). The smallest detectable change (1.8 TSS units) defined radiographic progression (∆TSS ≥ 2). Clinical remission (DAS28-CRP < 2.6) was assessed at baseline and 6 months. MBDA score was determined at 0 and 3 months and tested in a multivariable logistic regression model for predicting DAS28 remission at 6 months and radiographic progression at 1 year. RESULTS:Baseline MBDA score was independently associated with radiographic progression at 1 year [odds ratio (OR) = 1.03/unit, 95% confidence interval (CI) = 1.01-1.06], and changes in MBDA score from baseline to 3 months with clinical remission at 6 months [OR = 0.98/unit, 95% CI 0.96-1.00). In anti-cyclic citrullinated peptide antibody (anti-CCP)-positive patients, 35 of 89 with high MBDA score (> 44) showed radiographic progression (PPV = 39%), compared with 0 of 15 patients (NPV = 100%) with low/moderate MBDA score (≤ 44) (p = 0.003). CONCLUSION: Early changes in MBDA score were associated with clinical remission based on DAS28-CRP at 6 months. In anti-CCP-positive patients, a non-high baseline MBDA score (≤ 44) had a clinical value by predicting very low risk of radiographic progression at 12 months.
RCT Entities:
OBJECTIVES: Measurement of serum biomarkers at disease onset may improve prediction of disease course in patients with early rheumatoid arthritis (RA). We evaluated the multi-biomarker disease activity (MBDA) score and early changes in MBDA score for prediction of 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) remission and radiographic progression in the double-blinded OPERA trial. METHOD: Treatment-naïve RApatients (N = 180) with moderate or high DAS28 were randomized to methotrexate (MTX) + adalimumab (n = 89) or MTX + placebo (n = 91) in combination with glucocorticoid injection into swollen joints. X-rays of hands and feet were evaluated at months 0 and 12 (n = 164) by the total Sharp van der Heijde score (TSS). The smallest detectable change (1.8 TSS units) defined radiographic progression (∆TSS ≥ 2). Clinical remission (DAS28-CRP < 2.6) was assessed at baseline and 6 months. MBDA score was determined at 0 and 3 months and tested in a multivariable logistic regression model for predicting DAS28 remission at 6 months and radiographic progression at 1 year. RESULTS: Baseline MBDA score was independently associated with radiographic progression at 1 year [odds ratio (OR) = 1.03/unit, 95% confidence interval (CI) = 1.01-1.06], and changes in MBDA score from baseline to 3 months with clinical remission at 6 months [OR = 0.98/unit, 95% CI 0.96-1.00). In anti-cyclic citrullinated peptide antibody (anti-CCP)-positive patients, 35 of 89 with high MBDA score (> 44) showed radiographic progression (PPV = 39%), compared with 0 of 15 patients (NPV = 100%) with low/moderate MBDA score (≤ 44) (p = 0.003). CONCLUSION: Early changes in MBDA score were associated with clinical remission based on DAS28-CRP at 6 months. In anti-CCP-positive patients, a non-high baseline MBDA score (≤ 44) had a clinical value by predicting very low risk of radiographic progression at 12 months.
Authors: Amir A Razmjou; Jenny Brook; David Elashoff; Gurjit Kaeley; Soo Choi; Tanaz Kermani; Veena K Ranganath Journal: BMC Rheumatol Date: 2020-10-19
Authors: Jeffrey R Curtis; Michael E Weinblatt; Nancy A Shadick; Cecilie H Brahe; Mikkel Østergaard; Merete Lund Hetland; Saedis Saevarsdottir; Megan Horton; Brent Mabey; Darl D Flake; Rotem Ben-Shachar; Eric H Sasso; T W Huizinga Journal: Arthritis Res Ther Date: 2021-01-04 Impact factor: 5.156