Date: Monday, November 8, 2021
Session Type: Poster Session C
Session Time: 8:30AM-10:30AM
Background/Purpose: Belimumab is the only approved targeted treatment for systemic lupus erythematosus (SLE). Identification of early predictors of response or non-response to therapy is imperative to optimize surveillance and decision-making. We studied early changes in B cell subsets in relation to flare during standard therapy plus belimumab or placebo given to patients with active SLE within the frame of three phase III clinical trials of belimumab.
Methods: 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 flare was evaluated according to the SELENA-SLEDAI Flare Index every fourth week. We investigated B cell changes relative to baseline using proportional hazards regression analysis.
Results: Early 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 a severe flare during the study period, i.e. through week 52 from treatment initiation. A similar trend was seen for decreases in naïve CD19+CD20+CD27– B cells (HR: 0.7; 95% CI: 0.56–1.00; P=0.051). No such association was observed for early changes in the total CD19+CD20+ B cell pool, or in CD19+CD20+CD27+ memory B cells, CD19+CD20+CD69+ activated B cells, CD19+CD20+CD138+ 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 (any dose) (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 a lower probability to flare (HR: 0.6; 95% CI: 0.38–0.87; P=0.009).
Conclusion: 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 SLE-associated plasma cells may prove a useful early biological marker of favorable response to belimumab therapy.
To cite this abstract in AMA style:Parodis I, Gomez A, Lindblom J, Borg A, Emamikia S, gatto M. Associations Between Early Changes in Circulating B Cell Subsets and Severe Flare in Systemic Lupus Erythematosus – Results from Three Phase III Trials of Belimumab [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10). https://acrabstracts.org/abstract/associations-between-early-changes-in-circulating-b-cell-subsets-and-severe-flare-in-systemic-lupus-erythematosus-results-from-three-phase-iii-trials-of-belimumab/. Accessed January 28, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/associations-between-early-changes-in-circulating-b-cell-subsets-and-severe-flare-in-systemic-lupus-erythematosus-results-from-three-phase-iii-trials-of-belimumab/