Multi-biomarker disease activity score as a predictor of disease relapse in patients with rheumatoid arthritis stopping TNF inhibitor treatment

Marjan Ghiti Moghadam (Corresponding Author), Femke B.G. Lamers-Karnebeek, Harald E. Vonkeman, Peter M. ten Klooster, Janneke Tekstra, Annemarie M. Schilder, Henk Visser, Eric H. Sasso, David Chernoff, Willem F. Lems, Dirk-Jan van Schaardenburg, Robert Landewe, Hein J. Bernelot Moens, Timothy R.D.J. Radstake, Piet L.C.M. van Riel, Mart A.F.J. van de Laar, Tim L. Jansen,

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Abstract

Objective: Successfully stopping or reducing treatment for patients with rheumatoid arthritis (RA) in low disease activity (LDA) may improve cost-effectiveness of care. We evaluated the multi-biomarker disease activity (MBDA) score as a predictor of disease relapse after discontinuation of TNF inhibitor (TNFi) treatment.

Methods: 439 RA patients who were randomized to stop TNFi treatment in the POET study were analyzed post-hoc. Three indicators of disease relapse were assessed over 12 months: 1) restarting TNFi treatment, 2) escalation of any DMARD therapy and 3) physician-reported flare. MBDA score was assessed at baseline. Associations between MBDA score and disease relapse were examined using univariate analysis and multivariate logistic regression.

Results: At baseline, 50.1%, 35.3% and 14.6% of patients had low (<30), moderate (30−44) or high (>44) MBDA scores. Within 12 months, 49.9% of patients had restarted TNFi medication, 59.0% had escalation of any DMARD and 57.2% had 1 physician-reported flare. MBDA score was associated with each indicator of relapse. At least one indicator of relapse was observed in 59.5%, 68.4% and 81.3% of patients with low, moderate or high MBDA scores, respectively (P = 0.004). Adjusted for baseline DAS28-ESR, disease duration, BMI and erosions, high MBDA scores were associated with increased risk for restarting TNFi treatment (OR = 1.85, 95% CI 1.00–3.40), DMARD escalation (OR = 1.99, 95% CI 1.01–3.94) and physician-reported flare (OR = 2.00, 95% 1.06–3.77).

Conclusion: For RA patients with stable LDA who stopped TNFi, a high baseline MBDA score was independently predictive of disease relapse within 12 months. The MBDA score may be useful for identifying patients at risk of relapse after TNFi discontinuation.

Original languageEnglish
Article numbere0192425
JournalPLoS ONE
Volume13
Issue number5
DOIs
Publication statusPublished - 23 May 2018

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rheumatoid arthritis
relapse
Biomarkers
biomarkers
Rheumatoid Arthritis
Recurrence
physicians
Therapeutics
Antirheumatic Agents
Physicians
cost effectiveness
drug therapy
therapeutics
duration
Cost effectiveness

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Moghadam, Marjan Ghiti ; Lamers-Karnebeek, Femke B.G. ; Vonkeman, Harald E. ; ten Klooster, Peter M. ; Tekstra, Janneke ; Schilder, Annemarie M. ; Visser, Henk ; Sasso, Eric H. ; Chernoff, David ; Lems, Willem F. ; van Schaardenburg, Dirk-Jan ; Landewe, Robert ; Bernelot Moens, Hein J. ; Radstake, Timothy R.D.J. ; van Riel, Piet L.C.M. ; van de Laar, Mart A.F.J. ; Jansen, Tim L. / Multi-biomarker disease activity score as a predictor of disease relapse in patients with rheumatoid arthritis stopping TNF inhibitor treatment. In: PLoS ONE. 2018 ; Vol. 13, No. 5.
@article{ec62c40032fd441993d37f462caab12e,
title = "Multi-biomarker disease activity score as a predictor of disease relapse in patients with rheumatoid arthritis stopping TNF inhibitor treatment",
abstract = "Objective: Successfully stopping or reducing treatment for patients with rheumatoid arthritis (RA) in low disease activity (LDA) may improve cost-effectiveness of care. We evaluated the multi-biomarker disease activity (MBDA) score as a predictor of disease relapse after discontinuation of TNF inhibitor (TNFi) treatment.Methods: 439 RA patients who were randomized to stop TNFi treatment in the POET study were analyzed post-hoc. Three indicators of disease relapse were assessed over 12 months: 1) restarting TNFi treatment, 2) escalation of any DMARD therapy and 3) physician-reported flare. MBDA score was assessed at baseline. Associations between MBDA score and disease relapse were examined using univariate analysis and multivariate logistic regression.Results: At baseline, 50.1{\%}, 35.3{\%} and 14.6{\%} of patients had low (<30), moderate (30−44) or high (>44) MBDA scores. Within 12 months, 49.9{\%} of patients had restarted TNFi medication, 59.0{\%} had escalation of any DMARD and 57.2{\%} had 1 physician-reported flare. MBDA score was associated with each indicator of relapse. At least one indicator of relapse was observed in 59.5{\%}, 68.4{\%} and 81.3{\%} of patients with low, moderate or high MBDA scores, respectively (P = 0.004). Adjusted for baseline DAS28-ESR, disease duration, BMI and erosions, high MBDA scores were associated with increased risk for restarting TNFi treatment (OR = 1.85, 95{\%} CI 1.00–3.40), DMARD escalation (OR = 1.99, 95{\%} CI 1.01–3.94) and physician-reported flare (OR = 2.00, 95{\%} 1.06–3.77).Conclusion: For RA patients with stable LDA who stopped TNFi, a high baseline MBDA score was independently predictive of disease relapse within 12 months. The MBDA score may be useful for identifying patients at risk of relapse after TNFi discontinuation.",
author = "Moghadam, {Marjan Ghiti} and Lamers-Karnebeek, {Femke B.G.} and Vonkeman, {Harald E.} and {ten Klooster}, {Peter M.} and Janneke Tekstra and Schilder, {Annemarie M.} and Henk Visser and Sasso, {Eric H.} and David Chernoff and Lems, {Willem F.} and {van Schaardenburg}, Dirk-Jan and Robert Landewe and {Bernelot Moens}, {Hein J.} and Radstake, {Timothy R.D.J.} and {van Riel}, {Piet L.C.M.} and {van de Laar}, {Mart A.F.J.} and Jansen, {Tim L.}",
year = "2018",
month = "5",
day = "23",
doi = "10.1371/journal.pone.0192425",
language = "English",
volume = "13",
journal = "PLoS ONE",
issn = "1932-6203",
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Moghadam, MG, Lamers-Karnebeek, FBG, Vonkeman, HE, ten Klooster, PM, Tekstra, J, Schilder, AM, Visser, H, Sasso, EH, Chernoff, D, Lems, WF, van Schaardenburg, D-J, Landewe, R, Bernelot Moens, HJ, Radstake, TRDJ, van Riel, PLCM, van de Laar, MAFJ, Jansen, TL 2018, 'Multi-biomarker disease activity score as a predictor of disease relapse in patients with rheumatoid arthritis stopping TNF inhibitor treatment' PLoS ONE, vol. 13, no. 5, e0192425. https://doi.org/10.1371/journal.pone.0192425

Multi-biomarker disease activity score as a predictor of disease relapse in patients with rheumatoid arthritis stopping TNF inhibitor treatment. / Moghadam, Marjan Ghiti (Corresponding Author); Lamers-Karnebeek, Femke B.G.; Vonkeman, Harald E.; ten Klooster, Peter M.; Tekstra, Janneke; Schilder, Annemarie M.; Visser, Henk; Sasso, Eric H.; Chernoff, David; Lems, Willem F.; van Schaardenburg, Dirk-Jan; Landewe, Robert; Bernelot Moens, Hein J.; Radstake, Timothy R.D.J.; van Riel, Piet L.C.M.; van de Laar, Mart A.F.J.; Jansen, Tim L.

In: PLoS ONE, Vol. 13, No. 5, e0192425, 23.05.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Multi-biomarker disease activity score as a predictor of disease relapse in patients with rheumatoid arthritis stopping TNF inhibitor treatment

AU - Moghadam, Marjan Ghiti

AU - Lamers-Karnebeek, Femke B.G.

AU - Vonkeman, Harald E.

AU - ten Klooster, Peter M.

AU - Tekstra, Janneke

AU - Schilder, Annemarie M.

AU - Visser, Henk

AU - Sasso, Eric H.

AU - Chernoff, David

AU - Lems, Willem F.

AU - van Schaardenburg, Dirk-Jan

AU - Landewe, Robert

AU - Bernelot Moens, Hein J.

AU - Radstake, Timothy R.D.J.

AU - van Riel, Piet L.C.M.

AU - van de Laar, Mart A.F.J.

AU - Jansen, Tim L.

PY - 2018/5/23

Y1 - 2018/5/23

N2 - Objective: Successfully stopping or reducing treatment for patients with rheumatoid arthritis (RA) in low disease activity (LDA) may improve cost-effectiveness of care. We evaluated the multi-biomarker disease activity (MBDA) score as a predictor of disease relapse after discontinuation of TNF inhibitor (TNFi) treatment.Methods: 439 RA patients who were randomized to stop TNFi treatment in the POET study were analyzed post-hoc. Three indicators of disease relapse were assessed over 12 months: 1) restarting TNFi treatment, 2) escalation of any DMARD therapy and 3) physician-reported flare. MBDA score was assessed at baseline. Associations between MBDA score and disease relapse were examined using univariate analysis and multivariate logistic regression.Results: At baseline, 50.1%, 35.3% and 14.6% of patients had low (<30), moderate (30−44) or high (>44) MBDA scores. Within 12 months, 49.9% of patients had restarted TNFi medication, 59.0% had escalation of any DMARD and 57.2% had 1 physician-reported flare. MBDA score was associated with each indicator of relapse. At least one indicator of relapse was observed in 59.5%, 68.4% and 81.3% of patients with low, moderate or high MBDA scores, respectively (P = 0.004). Adjusted for baseline DAS28-ESR, disease duration, BMI and erosions, high MBDA scores were associated with increased risk for restarting TNFi treatment (OR = 1.85, 95% CI 1.00–3.40), DMARD escalation (OR = 1.99, 95% CI 1.01–3.94) and physician-reported flare (OR = 2.00, 95% 1.06–3.77).Conclusion: For RA patients with stable LDA who stopped TNFi, a high baseline MBDA score was independently predictive of disease relapse within 12 months. The MBDA score may be useful for identifying patients at risk of relapse after TNFi discontinuation.

AB - Objective: Successfully stopping or reducing treatment for patients with rheumatoid arthritis (RA) in low disease activity (LDA) may improve cost-effectiveness of care. We evaluated the multi-biomarker disease activity (MBDA) score as a predictor of disease relapse after discontinuation of TNF inhibitor (TNFi) treatment.Methods: 439 RA patients who were randomized to stop TNFi treatment in the POET study were analyzed post-hoc. Three indicators of disease relapse were assessed over 12 months: 1) restarting TNFi treatment, 2) escalation of any DMARD therapy and 3) physician-reported flare. MBDA score was assessed at baseline. Associations between MBDA score and disease relapse were examined using univariate analysis and multivariate logistic regression.Results: At baseline, 50.1%, 35.3% and 14.6% of patients had low (<30), moderate (30−44) or high (>44) MBDA scores. Within 12 months, 49.9% of patients had restarted TNFi medication, 59.0% had escalation of any DMARD and 57.2% had 1 physician-reported flare. MBDA score was associated with each indicator of relapse. At least one indicator of relapse was observed in 59.5%, 68.4% and 81.3% of patients with low, moderate or high MBDA scores, respectively (P = 0.004). Adjusted for baseline DAS28-ESR, disease duration, BMI and erosions, high MBDA scores were associated with increased risk for restarting TNFi treatment (OR = 1.85, 95% CI 1.00–3.40), DMARD escalation (OR = 1.99, 95% CI 1.01–3.94) and physician-reported flare (OR = 2.00, 95% 1.06–3.77).Conclusion: For RA patients with stable LDA who stopped TNFi, a high baseline MBDA score was independently predictive of disease relapse within 12 months. The MBDA score may be useful for identifying patients at risk of relapse after TNFi discontinuation.

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U2 - 10.1371/journal.pone.0192425

DO - 10.1371/journal.pone.0192425

M3 - Article

VL - 13

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 5

M1 - e0192425

ER -