@article{Liang:2026:10.1016/j.joca.2026.07.002,
author = {Liang, J and Papadaki, A and Vincent, TL and Conaghan, PG and Kingsbury, SR and Watt, F},
doi = {10.1016/j.joca.2026.07.002},
journal = {Osteoarthritis and Cartilage},
pages = {1539--1549},
title = {Systemic biomarkers of treatment response to methotrexate in people with painful knee osteoarthritis: a biological substudy of the PROMOTE randomised controlled clinical trial},
url = {http://dx.doi.org/10.1016/j.joca.2026.07.002},
volume = {34},
year = {2026}
}

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TY  - JOUR
AB  - ObjectiveStratification of therapeutic responses may help identify efficacious therapies for osteoarthritis (OA). In the PROMOTE randomised trial, participants with elevated baseline high-sensitivity C-reactive protein (hs-CRP) showed greater pain reduction after methotrexate treatment. We set out to interrogate a broader panel of serum/plasma inflammatory response markers relevant to methotrexate actions as potential biomarkers of therapeutic effect. Our objectives were to: (i) characterize changes in these systemic markers during methotrexate treatment; determine whether (ii) baseline levels or (iii) changes in any marker during treatment were associated with treatment response; and (iv) compare these findings with the more established clinical inflammatory marker, hs-CRP.DesignPlasma/serum samples from participants in PROMOTE’s biological substudy were analysed for 35 inflammatory markers at baseline (pre-treatment) and at 6-months (post-treatment), by MesoScale V-plex multiplex assay. Those with paired biological and clinical data at both baseline and 6-months were included in the substudy analysis set. Relationships between markers and overall data structure were assessed by Pearson correlation and Principal Component analysis. Associations between markers (baseline levels or change over time) and change in average knee pain severity in past week (numerical rating scale, NRS) were evaluated by univariable linear regression, adjusting for baseline age, sex, and body mass index. Least Absolute Shrinkage and Selection Operator (LASSO) regression with bootstrap resampling enabled marker selection. Benjamini-Hochberg correction adjusted for multiple testing (Padj).Results87 participants with paired blood marker and clinical data were eligible for substudy analysis. 18/35 markers were quantifiable and analysed. Systemic IL-8 and TNF-α levels decreased (Padj=0.015, 0.048 respectively) while IL-15 increased (Padj=0.033) with methotrexate treatment over 6-mo
AU  - Liang,J
AU  - Papadaki,A
AU  - Vincent,TL
AU  - Conaghan,PG
AU  - Kingsbury,SR
AU  - Watt,F
DO  - 10.1016/j.joca.2026.07.002
EP  - 1549
PY  - 2026///
SN  - 1063-4584
SP  - 1539
TI  - Systemic biomarkers of treatment response to methotrexate in people with painful knee osteoarthritis: a biological substudy of the PROMOTE randomised controlled clinical trial
T2  - Osteoarthritis and Cartilage
UR  - http://dx.doi.org/10.1016/j.joca.2026.07.002
VL  - 34
ER  - 

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