Lupus & antiphospholipid syndrome
Effect of upadacitinib and ABBV-599 on biomarkers in SLE: results from the phase 2 SLEek study
Authors' conclusion
Upadacitinib was associated with a reduction in both autoantibody and B-cell activation and with key gene expression changes in SLE pathogenic pathways. Dual JAK/BTK inhibition did not provide additional impact on most immunological parameters. These findings support JAK inhibition as a targeted monotherapy for SLE.
Study context
- Population
- Adults with moderately to severely active SLEThis analysis includes patients who received upadacitinib 30 mg, ABBV-599 or placebo
- Participants
- 62 / 68 / 75
- Comparison
- Upadacitinib 30 mg or ABBV-599 (upadacitinib 30 mg plus elsubrutinib 60 mg) vs placebo; biomarker and gene expression changes over 24 weeks
- UPADACITINIBn = 62
- ABBV-599n = 68
- PLACEBOn = 75
Primary result
As reported in the abstract
Anti-double-stranded DNA autoantibody levels · through week 24
- Both upadacitinib and ABBV-599 significantly reduced and sustained lower levels compared with baseline
Further findings
Plasma cell percentages
- Upadacitinib monotherapy alone reduced plasma cell percentages
Proteomic analysis
- Proteins modulated, including reductions in interferon-related and B-cell-associated proteins
- 301
RNA sequencing
- Significant changes in interferon, plasma cells and cell cycle gene modules correlating with clinical biomarkers
Original publication
Effect of upadacitinib and ABBV-599 on biomarkers in SLE: results from the phase 2 SLEek study. Lupus Sci Med. Published 29 October 2026. doi:10.
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