We aimed to investigate early changes in B cell subsets in relation to flare during standard therapy plus belimumab or placebo within the frame of three phase III clinical trials of belimumab in SLE.
We analyzed pooled 52-week data from BLISS-76 (N=819), BLISS-SC (N=836), and BLISS North-East Asia (N=60). B cell subsets were determined with flow-cytometry. Severe flares were evaluated according to the SELENA-SLEDAI Flare Index. We investigated B cell changes relative to baseline using proportional hazards regression.
Decreases in CD19+CD20-CD138+ long-lived (HR: 0.7; 95% CI: 0.56–0.98; P=0.034) and CD19+CD38brightCD27bright SLE-associated plasma cells (HR: 0.7; 95% CI: 0.50–0.87; P=0.003) from baseline through week 24 were negatively associated with the development of severe flare through week 52, and decreases in naïve CD19+CD20+CD27- B cells showed a similar trend (HR: 0.7; 95% CI: 0.56–1.00; P=0.051). No such association was observed for early changes in CD19+CD20+CD27+ memory B cells, CD19+CD20+CD69+ activated B cells or CD19+CD20-CD27bright short-lived plasma cells. The association with CD19+CD38brightCD27bright SLE-associated plasma cells held true for patients treated with belimumab (HR: 0.7; 95% CI: 0.47–0.97; P=0.032) but not placebo, while placebo receivers showing reductions in CD19+CD20-CD138+ long-lived plasma cells displayed lower probability to flare (HR: 0.6; 95% CI: 0.38–0.87; P=0.009).
Early decreases in long-lived circulating plasma cells were negatively associated with severe flares in patients with active SLE treated with standard immunosuppression with or without add-on belimumab, while reductions in circulating CD19+CD38brightCD27bright plasma cells may prove a useful early marker of favorable response to belimumab therapy.