Karen Hambardzumyan1,2, Rebecca J Bolce1,2, Johan K Wallman1,2, Ronald F van Vollenhoven1,2, Saedis Saevarsdottir3,4. 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 onMTX. Four of the 12 biomarkers [C-reactive protein (CRP), leptin, tumor necrosis factor receptorI (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].
RCT Entities:
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].
Authors: Yolima Puentes-Osorio; Pedro Amariles; Miguel Ángel Calleja; Vicente Merino; Juan Camilo Díaz-Coronado; Daniel Taborda Journal: Auto Immun Highlights Date: 2021-05-31
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