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Serum biomarkers for prediction of response to methotrexate monotherapy in early rheumatoid arthritis : Results from the SWEFOT trial

Hambardzumyan, Karen; Bolce, Rebecca J.; Wallman, Johan K. LU ; Van Vollenhoven, Ronald F. and Saevarsdottir, Saedis (2019) In Journal of Rheumatology 46(6). p.555-563
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
BIOMARKERS, METHOTREXATE RESPONSE, RHEUMATOID ARTHRITIS PREDICTION
in
Journal of Rheumatology
volume
46
issue
6
pages
9 pages
publisher
J Rheumatol Publ Co
external identifiers
  • scopus:85066427849
ISSN
0315-162X
DOI
10.3899/jrheum.180537
language
English
LU publication?
yes
id
3efc46dd-bbc8-4a57-94ec-42a781949adf
date added to LUP
2019-07-04 12:07:44
date last changed
2019-07-09 04:51:52
@article{3efc46dd-bbc8-4a57-94ec-42a781949adf,
  abstract     = {<p>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.</p>},
  author       = {Hambardzumyan, Karen and Bolce, Rebecca J. and Wallman, Johan K. and Van Vollenhoven, Ronald F. and Saevarsdottir, Saedis},
  issn         = {0315-162X},
  keyword      = {BIOMARKERS,METHOTREXATE RESPONSE,RHEUMATOID ARTHRITIS PREDICTION},
  language     = {eng},
  number       = {6},
  pages        = {555--563},
  publisher    = {J Rheumatol Publ Co},
  series       = {Journal of Rheumatology},
  title        = {Serum biomarkers for prediction of response to methotrexate monotherapy in early rheumatoid arthritis : Results from the SWEFOT trial},
  url          = {http://dx.doi.org/10.3899/jrheum.180537},
  volume       = {46},
  year         = {2019},
}