Impact of early changes in B cells on efficacy and safety over the entire treatment period (mITT population)
| Biomarker | Number of SRI-4 responses* | Number of serious/severe infections* |
| B cells (CD19+) | 0.97 (0.89 to 1.05) | 1.25 (0.88 to 1.79) |
| B cells (CD20+) | 0.96 (0.88 to 1.05) | 1.16 (0.83 to 1.64) |
| Naïve B cells (CD19+/CD20+/CD27−) | 0.94 (0.85 to 1.03) | 1.18 (0.78 to 1.78) |
| Memory B cells (CD19+/CD20+/CD27+) | 0.98 (0.89 to 1.07) | 1.20 (0.87 to 1.66) |
| Activated B cells (CD20+/CD69+) | 0.93 (0.85 to 1.01) | 1.12 (0.77 to 1.62) |
| Plasmacytoid B cells (CD19+/CD20+/CD138+) | 0.92 (0.85 to 1.01) | 1.19 (0.86 to 1.65) |
| SLE subset plasma cells (CD19+/CD27bright+/38bright+) | 1.00 (0.92 to 1.09) | 1.03 (0.73 to 1.45) |
| Short-lived plasma B cells (CD19+/CD20−/CD27bright+) | 1.01 (0.92 to 1.10) | 0.95 (0.69 to 1.32) |
| Plasma B cells (CD19+/CD20-/CD138+) | 0.98 (0.90 to 1.07) | 1.15 (0.80 to 1.66) |
| IgG | 0.90 (0.82 to 0.98)† | 0.83 (0.59 to 1.18) |
Rate ratios are calculated from a negative binomial regression model with offset log of follow-up time that includes terms for age, body mass index, baseline SLEDAI, baseline immunosuppressant use, treatment group and change from baseline at 6 months biomarker tertile.
Tertile definitions are shown in online supplemental table S1.
Most extreme reductions are in tertile 1 (ie, a value of 0.90 indicates that the probability of response is reduced by 0.9 for a patient in tertile 2 compared with tertile 1, and by 0.81=0.9*0.9 for patients in tertile 3 compared with tertile 1 while holding all other variables in the model constant).
*Rate ratio per tertile increase and 95% CIs based on the percent change from baseline at 6 months biomarker tertile.
†Statistical significance at 0.05 level.
CD, cluster of differentiation; mITT, modified intention-to-treat; SLEDAI, SLE Disease Activity Index; SRI, SLE Responder Index responses.