High MDR1 expression in RA is associated with increased MMP-3 levels and use of bDMARDs: potential independence of Janus kinase (JAK) inhibitors from MDR1
Authors' conclusion
High MDR1 expression correlates with elevated MMP-3 levels and more frequent bDMARDs use. JAK inhibitors remain effective regardless of MDR1 status, potentially bypassing MDR1-mediated cellular drug resistance in RA.
Study context
- Population
- RA patients undergoing total knee arthroplasty, October 2020 to June 202441 in primary analysis
- Participants
- 53 patients
- Comparison
- High vs low synovial MDR1 expression in RA; JAKi, bucillamine or verapamil in cultured synoviocytes
- High-MDR1n = 6
- Lowest MDR1 expressionn = 6reference
- Outcome
- Correlates of high MDR1 expression (multiple regression)
Methodological detailssynovial tissue from total knee arthroplasty, multiple regression analysis, in vitro fibroblast-like synoviocyte culture
- Synovial tissue from total knee arthroplasty
- Multiple regression analysis
- In vitro fibroblast-like synoviocyte culture
Main finding
As reported in the abstract
Elevated serum MMP-3 levels: β
−0.0010
95% CI −0.0019 to −0.0001P = 0.030
Increased use of bDMARDs: β
−0.406
95% CI −0.727 to −0.086P = 0.015
Further findings
In vitro drug effects on synoviocyte gene expression by MDR1 status
- Bucillamine suppressed MMP1, MMP3, ICAM1 and MCP1 expression less effectively in the high-MDR1 group, an effect reversed by verapamil
- All JAKi consistently suppressed cytokine expression regardless of MDR1 status
Parts of this Brief are withheld: the automatic checks could not confirm them against the abstract.
Original publication
High MDR1 expression in RA is associated with increased MMP-3 levels and use of bDMARDs: potential independence of JAK inhibitors from MDR1. Rheumatology (Oxford). Published 21 November 2025. doi:10.
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