Differential regulation of SOCS signalling and immunoproteasome pathways by janus kinase (JAK) inhibitors and TNF inhibitors in rheumatoid arthritis
Authors' conclusion
JAK inhibition drives a treatment-specific suppression of SOCS family members not observed under TNFi, reflecting differential remodelling of cytokine feedback networks. Baseline and early SOCS3 dynamics emerge as candidate biomarkers of treatment response.
Study context
- Population
- Patients with rheumatoid arthritis (RA); mRNA of SOCS1, SOCS2, SOCS3, CIS1 and immunoproteasome subunit β2i in PBMCs by real-time PCR
- Participants
- 75 patients2 prospective cohorts
- Exposure
- Baricitinib vs tofacitinib vs TNF inhibitors (TNFi) in RA, with healthy donors as controls
- Tofacitinibn = 15
- Baricitinibn = 29
- TNFin = 31
- Outcome
- SOCS/proteasome molecular signatures under treatment
Methodological detailspilot study, two prospective cohorts (inception and confirmatory), healthy donor controls
- Pilot study
- Two prospective cohorts (inception and confirmatory)
- Healthy donor controls
Main finding
As reported in the abstract
- SOCS2 mRNA declined progressively under both baricitinib and tofacitinib but not under TNFi
- SOCS1 and SOCS3 mRNA normalized under baricitinib over time; SOCS3 elevation persisted throughout observation under TNFi
- CIS1 selectively suppressed under baricitinib
- Partial discordance between SOCS2 mRNA and protein levels, suggesting post-transcriptional regulation
- Proteasomal β2i mRNA relatively upregulated under tofacitinib and TNFi but not under baricitinib
Observational data: associations, not effects.
Further findings
Responder rates · both time points
- Comparable across all three treatment groups
SOCS3 and treatment response
- Baseline SOCS3 significantly higher in baricitinib non-responders than responders
- Early SOCS3 decline at 2 weeks distinguished TNFi responders from non-responders
Original publication
Differential regulation of SOCS signalling and immunoproteasome pathways by JAK inhibitors and TNF inhibitors in rheumatoid arthritis. Arthritis Res Ther. Published 15 September 2026. doi:10.
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