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Early Increase in Circulating Memory B Cells Portends Clinical Response to Treatment in Pooled Data from Three Phase III Trials of Belimumab
Örebro University, School of Medical Sciences. Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.ORCID iD: 0000-0002-4875-5395
Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
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2021 (English)In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 73, no Suppl. 9, p. 2695-2696, article id 1301Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background/Purpose: Belimumab blocks soluble B cell activating factor (BAFF) and is the only to date approved targeted treatment for systemic lupus erythematosus (SLE). Identification of biological predictors of response occurring earlier upon treatment would provide measurable tools to improve patient monitoring and stratification according to likelihood of response. We investigated early changes in B lymphocyte subsets in relation to response to standard therapy plus belimumab or placebo given to patients with active SLE and mainly musculoskeletal and mucocutaneous symptoms.

Methods: We analyzed pooled data from belimumab phase III clinical trials including BLISS-76 (N=819) and BLISS-SC (N=836); in addition, 60 patients from the BLISS North- East Asia trial were included in the analysis. B lymphocyte subsets were determined with flow cytometry. Treatment response was assessed using the composite measure SLE Responder Index 4 (SRI- 4), defined as decrease in SLEDAI by ≥4 points, no worsening in the physician’s global assessment by >30% and no new British Lupus Isles Assessment Group (BILAG) index (≥1 A or ≥2 B), at week 52. Additionally, persistence of SRI- 4 through week 52 was evaluated. We investigated B cell changes relative to baseline using logistic or proportional hazards regression analysis, as appropriate.

Results: We found an association between an early expansion of CD19+CD20+CD27+ memory B cells from baseline through week 8 and attainment of SRI- 4 response at week 52 (OR: 1.5; 95% CI: 1.18– 1.89; P=0.001), or for relative increases >10% (OR: 1.5; 95% CI: 1.17– 1.83; P=0.001). Expansion above this threshold of 10% was also associated with increased probability or shorter time to achieve SRI- 4 response that was maintained through week 52 (HR: 1.4; 95% CI: 1.15– 1.61; P< 0.001). Notably, belimumab treatment (any dose) yielded an 11.5- fold increased probability of memory B cell expansion through week 8 compared with placebo (95% CI: 8.74– 15.02; P< 0.001). No association with SRI- 4 response was observed for early changes in CD19+CD20+ B cells, CD19+CD20+CD27-  naïve B cells, CD19+CD20+CD69+ activated B cells, CD19+CD20- CD27bright short- lived plasma cells, CD19+CD20- CD138+ long- lived plasma cells, or CD19+CD38brightCD27bright SLE- associated plasma cells.

Conclusion: Early increases in memory B cells through the first 8 weeks of therapy, mainly driven by belimumab, portended good and sustained clinical response within one year from treatment initiation. Early immunological changes preceding the clinical outcome and may prove useful in early evaluation of belimumab therapy.

Place, publisher, year, edition, pages
John Wiley & Sons, 2021. Vol. 73, no Suppl. 9, p. 2695-2696, article id 1301
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:oru:diva-97874ISI: 000744545205083OAI: oai:DiVA.org:oru-97874DiVA, id: diva2:1643336
Conference
ACR Convergence 2021, (Virtual conference), November 5-9, 2021
Available from: 2022-03-09 Created: 2022-03-09 Last updated: 2022-03-09Bibliographically approved

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Parodis, Ioannis

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