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 H Sasso; L M 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 Ammitzbøll; A Jørgensen; S B Krintel; J Raun; M L Hetland

doi: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

C H Brahe, M Østergaard, J S Johansen, N Defranoux, X Wang, R Bolce, E H Sasso, L M 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 B Krintel, J Raun, M L Hetland

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 language	English
Journal	Scandinavian Journal of Rheumatology
Volume	48
Issue number	1
Pages (from-to)	9-16
Number of pages	8
ISSN	0300-9742
DOIs	https://doi.org/10.1080/03009742.2018.1464206
Publication status	Published - 2019

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

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10.1080/03009742.2018.1464206

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Brahe, C. H., Østergaard, M., Johansen, J. S., Defranoux, N., Wang, X., Bolce, R., Sasso, E. H., Ørnbjerg, L. M., 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., ... Hetland, M. L. (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, 48(1), 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 et al.
In: Scandinavian Journal of Rheumatology, Vol. 48, No. 1, 2019, p. 9-16.

Research output: Contribution to journal › Journal article › Research › peer-review

Brahe, CH , Østergaard, M , Johansen, JS, Defranoux, N, Wang, X, Bolce, R, Sasso, EH, Ørnbjerg, LM, 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, SB, Raun, J & Hetland, ML 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

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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 Sasso, {E H} and {\O}rnbjerg, {L M} 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 Krintel, {S B} and J Raun and Hetland, {M L}",

note = "COPECARE",

year = "2019",

doi = "10.1080/03009742.2018.1464206",

language = "English",

volume = "48",

pages = "9--16",

journal = "Scandinavian Journal of Rheumatology",

issn = "0300-9742",

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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 H

AU - Ørnbjerg, L M

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 B

AU - Raun, J

AU - Hetland, M L

N1 - COPECARE

PY - 2019

Y1 - 2019

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

SN - 0300-9742

VL - 48

SP - 9

EP - 16

JO - Scandinavian Journal of Rheumatology

JF - Scandinavian Journal of Rheumatology

IS - 1

ER -

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

Keywords

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