Personalized Healthcare in Autoimmune Diseases - Genomic Biomarkers for Pharmaceutical Development - page 58

FIGURE 3.4 An RA subgroup defined by an IgJ mRNA biomarker with reduced efficacy after anti-CD20 ther-
apy. (A) Baseline mRNA samples from the REFLEX trial of rituximab in RA were used to identify optimal bio-
marker thresholds for IgJ as a predictor of ACR50 response rates at 6 months (day 168) for subjects treated with
anti-CD20 (blue bars) or placebo (yellow bars). (B and C) This biomarker threshold (IgJ ≥0.1 or <0.1 expression
unit) was then tested prospectively in baseline mRNA samples from the DANCER (B) and SERENE (C) trials of
rituximab in RA. (D) Biomarker thresholds for the SCRIPT trial of ocrelizumab in RA were based on percentage
thresholds from the rituximab studies (see text for details). Δ in (A) to (D) denotes the ACR50 percentage difference
for the active anti-CD20 arm between the IgJ hi and the IgJ lo subgroups. n refers to the number of individual subjects
in each subgroup, and the number above the bars is the percent ACR50 for each subgroup. (E) ORs and 95% CI for
the enrichment of ACR50 responses in the IgJ lo subgroup compared to the IgJ hi subgroup for the individual trials,
the replication trials in aggregate (DANCER, SERENE, and SCRIPT), and all trials together are depicted.