PMID- 30709958
OWN - NLM
STAT- Publisher
LR  - 20190202
IS  - 0315-162X (Print)
IS  - 0315-162X (Linking)
DP  - 2019 Feb 1
TI  - Serum Biomarkers for Prediction of Response to Methotrexate Monotherapy in Early 
      Rheumatoid Arthritis: Results from the SWEFOT Trial.
LID - jrheum.180537 [pii]
LID - 10.3899/jrheum.180537 [doi]
AB  - 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].
FAU - Hambardzumyan, Karen
AU  - Hambardzumyan K
AD  - 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. This work was supported
      in part by a grant from the Swedish Rheumatism Association. Some of the authors
      were supported by clinical research funds from Stockholm County (ALF funds). An
      annual unrestricted grant was provided by Schering-Plough Sweden, which was used 
      to support a study coordinator and a medical monitor for the original clinical
      trial. RJB received consultancy fees from Crescendo Bioscience. 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. Address correspondence to Dr. S. Saevarsdottir, Unit of Translational
      Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Nobels 
      vag 13, SE-17165, Solna, Stockholm, Sweden. E-mail: saedis.saevarsdottir@ki.se.
      Accepted for publication October 9, 2018.
FAU - Bolce, Rebecca J
AU  - Bolce RJ
AD  - 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. This work was supported
      in part by a grant from the Swedish Rheumatism Association. Some of the authors
      were supported by clinical research funds from Stockholm County (ALF funds). An
      annual unrestricted grant was provided by Schering-Plough Sweden, which was used 
      to support a study coordinator and a medical monitor for the original clinical
      trial. RJB received consultancy fees from Crescendo Bioscience. 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. Address correspondence to Dr. S. Saevarsdottir, Unit of Translational
      Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Nobels 
      vag 13, SE-17165, Solna, Stockholm, Sweden. E-mail: saedis.saevarsdottir@ki.se.
      Accepted for publication October 9, 2018.
FAU - Wallman, Johan K
AU  - Wallman JK
AUID- ORCID: http://orcid.org/0000-0002-4915-2924
AD  - 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. This work was supported
      in part by a grant from the Swedish Rheumatism Association. Some of the authors
      were supported by clinical research funds from Stockholm County (ALF funds). An
      annual unrestricted grant was provided by Schering-Plough Sweden, which was used 
      to support a study coordinator and a medical monitor for the original clinical
      trial. RJB received consultancy fees from Crescendo Bioscience. 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. Address correspondence to Dr. S. Saevarsdottir, Unit of Translational
      Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Nobels 
      vag 13, SE-17165, Solna, Stockholm, Sweden. E-mail: saedis.saevarsdottir@ki.se.
      Accepted for publication October 9, 2018.
FAU - van Vollenhoven, Ronald F
AU  - van Vollenhoven RF
AUID- ORCID: http://orcid.org/0000-0001-6438-8663
AD  - 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. This work was supported
      in part by a grant from the Swedish Rheumatism Association. Some of the authors
      were supported by clinical research funds from Stockholm County (ALF funds). An
      annual unrestricted grant was provided by Schering-Plough Sweden, which was used 
      to support a study coordinator and a medical monitor for the original clinical
      trial. RJB received consultancy fees from Crescendo Bioscience. 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. Address correspondence to Dr. S. Saevarsdottir, Unit of Translational
      Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Nobels 
      vag 13, SE-17165, Solna, Stockholm, Sweden. E-mail: saedis.saevarsdottir@ki.se.
      Accepted for publication October 9, 2018.
FAU - Saevarsdottir, Saedis
AU  - Saevarsdottir S
AUID- ORCID: http://orcid.org/0000-0001-9392-6184
AD  - 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. This work was supported
      in part by a grant from the Swedish Rheumatism Association. Some of the authors
      were supported by clinical research funds from Stockholm County (ALF funds). An
      annual unrestricted grant was provided by Schering-Plough Sweden, which was used 
      to support a study coordinator and a medical monitor for the original clinical
      trial. RJB received consultancy fees from Crescendo Bioscience. 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. Address correspondence to Dr. S. Saevarsdottir, Unit of Translational
      Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Nobels 
      vag 13, SE-17165, Solna, Stockholm, Sweden. E-mail: saedis.saevarsdottir@ki.se.
      Accepted for publication October 9, 2018.
LA  - eng
SI  - ClinicalTrials.gov/NCT00764725
PT  - Journal Article
DEP - 20190201
PL  - Canada
TA  - J Rheumatol
JT  - The Journal of rheumatology
JID - 7501984
EDAT- 2019/02/03 06:00
MHDA- 2019/02/03 06:00
CRDT- 2019/02/03 06:00
PHST- 2019/02/03 06:00 [entrez]
PHST- 2019/02/03 06:00 [pubmed]
PHST- 2019/02/03 06:00 [medline]
AID - jrheum.180537 [pii]
AID - 10.3899/jrheum.180537 [doi]
PST - aheadofprint
SO  - J Rheumatol. 2019 Feb 1. pii: jrheum.180537. doi: 10.3899/jrheum.180537.