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J Rheumatol. 2019 Jun;46(6):555-563. doi: 10.3899/jrheum.180537. Epub 2019 Feb 1.

Serum Biomarkers for Prediction of Response to Methotrexate Monotherapy in Early Rheumatoid Arthritis: Results from the SWEFOT Trial.

Author information

1
From the Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Crescendo Bioscience, South San Francisco, California, USA; Section of Rheumatology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Amsterdam Rheumatology and Immunology Center, Amsterdam, the Netherlands; Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden.
2
K. Hambardzumyan, MSc, Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital; R.J. Bolce, MSN, Crescendo Bioscience; J.K. Wallman, MD, PhD, Section of Rheumatology, Department of Clinical Sciences Lund, Lund University; R.F. van Vollenhoven, MD, PhD, Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, and Amsterdam Rheumatology and Immunology Center; S. Saevarsdottir, MD, PhD, Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, and Unit of Translational Epidemiology, Institute of Environmental Medicine, Karolinska Institutet.
3
From the Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Crescendo Bioscience, South San Francisco, California, USA; Section of Rheumatology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Amsterdam Rheumatology and Immunology Center, Amsterdam, the Netherlands; Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden. saedis.saevarsdottir@ki.se.
4
K. Hambardzumyan, MSc, Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital; R.J. Bolce, MSN, Crescendo Bioscience; J.K. Wallman, MD, PhD, Section of Rheumatology, Department of Clinical Sciences Lund, Lund University; R.F. van Vollenhoven, MD, PhD, Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, and Amsterdam Rheumatology and Immunology Center; S. Saevarsdottir, MD, PhD, Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, and Unit of Translational Epidemiology, Institute of Environmental Medicine, Karolinska Institutet. saedis.saevarsdottir@ki.se.

Abstract

OBJECTIVE:

To investigate baseline levels of 12 serum biomarkers that constitute a multibiomarker disease activity test, as predictors of response to methotrexate (MTX) in patients with early rheumatoid arthritis (eRA).

METHODS:

In 298 patients from the Swedish Pharmacotherapy (SWEFOT) clinical trial, baseline serum levels of 12 proteins were analyzed for association with disease activity based on the 28-joint count Disease Activity Score (DAS28) after 3 months of MTX monotherapy using uni-/multivariate logistic regression. Primary outcome was low disease activity (LDA; DAS28 ≤ 3.2).

RESULTS:

Of 298 patients, 104 achieved LDA after 3 months on MTX. Four of the 12 biomarkers [C-reactive protein (CRP), leptin, tumor necrosis factor receptor I (TNF-RI), and vascular cell adhesion molecule 1 (VCAM-1)] significantly predicted LDA based on stepwise logistic regression analysis. Dichotomization of patients using receiver-operating characteristic curve analysis-based cutoffs for these biomarkers showed significantly higher proportions with LDA among patients with lower versus higher levels of CRP or leptin (40% vs 23%, p = 0.004, and 40% vs 25%, p = 0.011, respectively), as well as among those with higher versus lower levels of TNF-RI or VCAM-1 (43% vs 27%, p = 0.004, and 41% vs 25%, p = 0.004, respectively). Combined score based on these biomarkers, adjusted for known predictors of LDA (smoking, sex, and age), associated with decreased chance of LDA (adjusted OR 0.45, 95% CI 0.32-0.62).

CONCLUSION:

Low baseline levels of CRP and leptin, and high baseline levels of TNF-RI and VCAM-1 were associated with LDA after 3 months of MTX therapy in patients with eRA. Combination of these 4 biomarkers increased accuracy of prediction. [Trial registration number: NCT00764725].

KEYWORDS:

BIOMARKERS; METHOTREXATE; PREDICTION; RESPONSE; RHEUMATOID ARTHRITIS

PMID:
30709958
DOI:
10.3899/jrheum.180537

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