NK cell cytotoxicity is markedly reduced in younger patients with RA treated with JAK inhibitors
Authors' conclusion
JAKi treatment significantly impaired NK cell activity and differentiation in RA patients, with age influencing these effects, underscoring important safety concerns.
Study context
- Population
- RA patients with low disease activity (LDA) treated with Janus kinase inhibitors (JAKi) or TNF inhibitors (TNFi) for more than three months
- Participants
- 85 vs 131
- Exposure
- JAKi vs TNFi for more than three months
- JAKin = 85
- TNFin = 131reference
- Outcome
- Cytotoxic activity of peripheral blood NK cells (51Cr-release assay)
Methodological detailspropensity score matching, multivariable logistic regression, 51Cr-release assay, flow cytometry
- Propensity score matching
- Multivariable logistic regression
- 51Cr-release assay
- Flow cytometry
Main finding
As reported in the abstract
NK cell activity
- JAKi vs TNFi: P = 0.002
Observational data: associations, not effects.
Further findings
NK cell phenotype
- Proportion of NK and CD56dim cells reduced, CD56bright cells more abundant in JAKi
Independent risk factors for reduced NK cell activity in JAKi
- GC use, OR 5.36 (95% CI 1.10-26.07), P = 0.04
- Younger age (<50 years), OR 10.56 (95% CI 2.69-41.45), P < 0.01
Safety
Herpes zoster incidence, RA patients younger than 50 years
- Significantly higher in the low NK cell activity group
Original publication
NK cell cytotoxicity is markedly reduced in younger patients with RA treated with JAK inhibitors. Rheumatology (Oxford). Published 4 June 2025. doi:10.
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