Predictive value of a multi-biomarker disease activity score for clinical remission and radiographic progression in patients with early rheumatoid arthritis: a post-hoc study of the OPERA trial

C. H. Brahe, M. Østergaard, J. S. Johansen, N. Defranoux, X. Wang, R. Bolce, E. Sasso, L. Ørnbjerg, K. Hørslev-Petersen, K. Stengaard-Pedersen, P. Junker, T. Ellingsen, P. Ahlquist, H. Lindegaard, A. Linauskas, A. Schlemmer, M. Y. Dam, I. Hansen, T. Lottenburger, C. AmmitzbøllA. Jørgensen, S. Krintel, J. Raun, M. Hetland

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalScandinavian Journal of Rheumatology
Volume48
Issue number1
Pages (from-to)9-16
ISSN0300-9742
DOIs
Publication statusPublished - 2. Jan 2019

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Methotrexate
Joint Diseases
Glucocorticoids
Joints
Placebos
X-Rays
Serum
Adalimumab

Keywords

  • Adalimumab/therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Antirheumatic Agents/therapeutic use
  • Arthritis, Rheumatoid/blood
  • Biomarkers/blood
  • C-Reactive Protein/metabolism
  • Disease Progression
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents
  • Male
  • Methotrexate/therapeutic use
  • Middle Aged
  • Radiography
  • Remission Induction/methods
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult

Cite this

Brahe, C. H. ; Østergaard, M. ; Johansen, J. S. ; Defranoux, N. ; Wang, X. ; Bolce, R. ; Sasso, E. ; Ørnbjerg, L. ; Hørslev-Petersen, K. ; Stengaard-Pedersen, K. ; Junker, P. ; Ellingsen, T. ; Ahlquist, P. ; Lindegaard, H. ; Linauskas, A. ; Schlemmer, A. ; Dam, M. Y. ; Hansen, I. ; Lottenburger, T. ; Ammitzbøll, C. ; Jørgensen, A. ; Krintel, S. ; Raun, J. ; Hetland, M. / Predictive value of a multi-biomarker disease activity score for clinical remission and radiographic progression in patients with early rheumatoid arthritis : a post-hoc study of the OPERA trial. In: Scandinavian Journal of Rheumatology. 2019 ; Vol. 48, No. 1. pp. 9-16.
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title = "Predictive value of a multi-biomarker disease activity score for clinical remission and radiographic progression in patients with early rheumatoid arthritis: a post-hoc study of the OPERA trial",
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-na{\"i}ve 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.",
keywords = "Adalimumab/therapeutic use, Adult, Aged, Aged, 80 and over, Antirheumatic Agents/therapeutic use, Arthritis, Rheumatoid/blood, Biomarkers/blood, C-Reactive Protein/metabolism, Disease Progression, Double-Blind Method, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Immunosuppressive Agents, Male, Methotrexate/therapeutic use, Middle Aged, Radiography, Remission Induction/methods, Severity of Illness Index, Treatment Outcome, Young Adult",
author = "Brahe, {C. H.} and M. {\O}stergaard and Johansen, {J. S.} and N. Defranoux and X. Wang and R. Bolce and E. Sasso and L. {\O}rnbjerg and K. H{\o}rslev-Petersen and K. Stengaard-Pedersen and P. Junker and T. Ellingsen and P. Ahlquist and H. Lindegaard and A. Linauskas and A. Schlemmer and Dam, {M. Y.} and I. Hansen and T. Lottenburger and C. Ammitzb{\o}ll and A. J{\o}rgensen and S. Krintel and J. Raun and M. Hetland",
year = "2019",
month = "1",
day = "2",
doi = "10.1080/03009742.2018.1464206",
language = "English",
volume = "48",
pages = "9--16",
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}

Brahe, CH, Østergaard, M, Johansen, JS, Defranoux, N, Wang, X, Bolce, R, Sasso, E, Ørnbjerg, L, Hørslev-Petersen, K, Stengaard-Pedersen, K, Junker, P, Ellingsen, T, Ahlquist, P, Lindegaard, H, Linauskas, A, Schlemmer, A, Dam, MY, Hansen, I, Lottenburger, T, Ammitzbøll, C, Jørgensen, A, Krintel, S, Raun, J & Hetland, M 2019, 'Predictive value of a multi-biomarker disease activity score for clinical remission and radiographic progression in patients with early rheumatoid arthritis: a post-hoc study of the OPERA trial', Scandinavian Journal of Rheumatology, vol. 48, no. 1, pp. 9-16. https://doi.org/10.1080/03009742.2018.1464206

Predictive value of a multi-biomarker disease activity score for clinical remission and radiographic progression in patients with early rheumatoid arthritis : a post-hoc study of the OPERA trial. / Brahe, C. H.; Østergaard, M.; Johansen, J. S.; Defranoux, N.; Wang, X.; Bolce, R.; Sasso, E.; Ørnbjerg, L.; Hørslev-Petersen, K.; Stengaard-Pedersen, K.; Junker, P.; Ellingsen, T.; Ahlquist, P.; Lindegaard, H.; Linauskas, A.; Schlemmer, A.; Dam, M. Y.; Hansen, I.; Lottenburger, T.; Ammitzbøll, C.; Jørgensen, A.; Krintel, S.; Raun, J.; Hetland, M.

In: Scandinavian Journal of Rheumatology, Vol. 48, No. 1, 02.01.2019, p. 9-16.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Predictive value of a multi-biomarker disease activity score for clinical remission and radiographic progression in patients with early rheumatoid arthritis

T2 - a post-hoc study of the OPERA trial

AU - Brahe, C. H.

AU - Østergaard, M.

AU - Johansen, J. S.

AU - Defranoux, N.

AU - Wang, X.

AU - Bolce, R.

AU - Sasso, E.

AU - Ørnbjerg, L.

AU - Hørslev-Petersen, K.

AU - Stengaard-Pedersen, K.

AU - Junker, P.

AU - Ellingsen, T.

AU - Ahlquist, P.

AU - Lindegaard, H.

AU - Linauskas, A.

AU - Schlemmer, A.

AU - Dam, M. Y.

AU - Hansen, I.

AU - Lottenburger, T.

AU - Ammitzbøll, C.

AU - Jørgensen, A.

AU - Krintel, S.

AU - Raun, J.

AU - Hetland, M.

PY - 2019/1/2

Y1 - 2019/1/2

N2 - 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.

AB - 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.

KW - Adalimumab/therapeutic use

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antirheumatic Agents/therapeutic use

KW - Arthritis, Rheumatoid/blood

KW - Biomarkers/blood

KW - C-Reactive Protein/metabolism

KW - Disease Progression

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Immunosuppressive Agents

KW - Male

KW - Methotrexate/therapeutic use

KW - Middle Aged

KW - Radiography

KW - Remission Induction/methods

KW - Severity of Illness Index

KW - Treatment Outcome

KW - Young Adult

U2 - 10.1080/03009742.2018.1464206

DO - 10.1080/03009742.2018.1464206

M3 - Journal article

C2 - 29985080

AN - SCOPUS:85049613694

VL - 48

SP - 9

EP - 16

JO - Scandinavian Journal of Rheumatology

JF - Scandinavian Journal of Rheumatology

SN - 0300-9742

IS - 1

ER -