Lupus & antiphospholipid syndrome
Responsiveness of systemic lupus erythematosus subjects to iberdomide based on molecular endotypes
Authors' conclusion
Molecular profiles of SLE subjects identified pharmacodynamic effects of iberdomide that occurred in all endotypes as well as changes in specific gene modules altered in endotypes associated with a significant clinical response.
Study context
- Population
- Female systemic lupus erythematosus (SLE) subjects in the phase 2b iberdomide trial
- Participants
- 276 female SLE subjects
- Comparison
- Baseline molecular endotypes (A-E) of SLE subjects compared for clinical response to iberdomide and treatment-related gene expression changes
Methodological detailsRNA sequencing of whole blood, gene set variation analysis (GSVA) using 32 informative gene modules, unsupervised K-means clustering
- RNA sequencing of whole blood
- GSVA using 32 informative gene modules
- Unsupervised K-means clustering
Primary result
As reported in the abstract
Clinical response to iberdomide (SRI-4) by molecular endotype
- K-means clustering of GSVA scores yielded 5 endotypes (A-E) with increasing molecular abnormalities indicative of enhanced immune activity
- Significant clinical responses to iberdomide (SRI-4) confined to endotypes C and E
- Endotype E responders: most important treatment-related modules were Treg cells, B cells and interferon
- Endotype C: unfolded proteins, oxidative phosphorylation and anergic/activated T cells associated with responsiveness
Original publication
Responsiveness of systemic lupus erythematosus subjects to iberdomide based on molecular endotypes. Ann Rheum Dis. Published 27 February 2025. doi:10.
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