Pretreatment synovial transcriptional profile is associated with early and late clinical response in rheumatoid arthritis patients treated with rituximab
Annals of Rheumatic Diseases, 07/16/2012
Hogan VE et al. – This study reveals a baseline synovial GS that correlates with early and late clinical responses to rituximab. The gene score (GS) biology suggests that T cells and macrophages are important for response to B cell depleting therapy, while expression of remodelling and interferon–α genes correlates with poor response.Methods
- The authors studied synovial gene expression using high–throughput quantitative real–time–PCR in 20 RA patients who underwent arthroscopy before and after treatment with rituximab.
- Several objective approaches were used to explore patterns in the data and to find genes associated with changes in disease activity due to treatment.
- This analysis revealed two patient populations associated with distinct clinical, laboratory and histological features and, importantly, showed enrichment for response (60% non–responders vs 90% responders).
- A composite baseline gene score (GS) correlated with change in disease activity score (ΔDAS) between baseline and month 3 (r=0.74, p=0.0002), but also with ΔDAS at later time–points (month 9, r=0.54, p=0.016; month 15, r=0.45, p=0.06; month 21, r=0.72, p=0.003).
- Notably, the GS significantly correlated with baseline erythrocyte sedimentation rate (r=0.69, p=0.0008), but not with other DAS components.
- The GS genes represented T cell, macrophage, remodelling and interferon–α biology.
- Responders demonstrated higher expression of macrophage and T cell genes, while non–responders showed higher expression of interferon–α and remodelling genes.