Systemic biomarkers of treatment response to methotrexate in people with painful knee osteoarthritis: A biological substudy of the PROMOTE randomised controlled clinical trial
Authors' conclusion
Blood measurement of IFN-γ, TNF-α, IL-15 and IL-16 as well as hs-CRP could act as potential markers to stratify the treatment response by average knee pain to methotrexate in knee osteoarthritis.
Study context
- Population
- Participants with painful knee osteoarthritis (OA) in the PROMOTE trial's biological substudy with paired biological and clinical data at baseline and 6 months18/35 markers analysed
- Participants
- 87 participants
- Comparison
- Systemic inflammatory markers vs change in knee pain with MTX
- Primary endpoint
- Association of markers (baseline levels or change over time) with change in average knee pain severity in past week (NRS)
- Follow-up
- 6 months
Methodological detailsbiological substudy, univariable linear regression adjusted for age, sex and BMI, Least Absolute Shrinkage and Selection Operator (LASSO) regression with bootstrap resampling, Benjamini-Hochberg correction
- Biological substudy
- Univariable linear regression adjusted for age, sex and BMI
- LASSO regression with bootstrap resampling
- Benjamini-Hochberg correction
Primary result
As reported in the abstract
- IL-8 decreased with MTX over 6 months
- Padj=0.015
- TNF-α decreased with MTX over 6 months
- Padj=0.048
- IL-15 increased with MTX over 6 months
- Padj=0.033
- Higher baseline IFN-γ associated with greater reduction in NRS pain
- 0.66 [0.01, 1.31], P=0.047
- Decreasing TNF-α over 6 months associated with greater reduction in NRS pain
- 2.25 [0.00, 4.5], P=0.049
Further findings
Treatment arm-by-biomarker interaction (high-sensitivity C-reactive protein (hs-CRP)), adjusted
- Only hs-CRP of 19 markers showed consistent effects; baseline coefficient
- 2.34 [0.53, 4.15], P=0.001
- hs-CRP change over 6 months
- 0.36 [0.06, 0.66], P=0.018
- Secondary univariate analysis
Original publication
Systemic biomarkers of treatment response to methotrexate in people with painful knee osteoarthritis: A biological substudy of the PROMOTE randomised controlled clinical trial. Osteoarthritis Cartilage. Published 7 July 2026. doi:10.
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