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Delayed action of Benlysta may be linked with CD27+ B cells, BAFFR in patients with SLE

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A delayed response to treatment with Benlysta may be due to an initial increase in CD27+ B cells, followed by a decrease, resulting in lower expression of B cell activating factor receptor in patients with systemic lupus erythematosus, according to results of a recently presented study.

Researchers studied seven patients with systemic lupus erythematosus (SLE) who began treatment with Benlysta (belimumab, GSK) in May 2013. All patients were women, with a mean age of 46.7 years and a mean disease duration of 13.8 years. At least two immunosuppressants had been used by all patients prior to study entry, and all received corticosteroids at entry. Six received at least one immunosuppressant. At baseline, the mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) score was 9.7.

Blood samples were collected for analysis at baseline and at months 3, 6, 9 and 12. Multiparametric flow cytometry on a BD FACSCanto flow cytometer (BD Biosciences) was used to detect B cells, and B cell activating factor receptor (BAFFR) expression was analyzed as mean fluorescence intensity (MFI).

Mean SELENA-SLEDAI scores decreased from 9.7 at baseline to 6.1 at month 3, to 5 at month 6, to 4.4 at month 9 and to 4.1 at month 12. At baseline, CD19+ cells were low in number, according to the researchers. CD19+CD27- cells decreased from mean 60 cells/µL at baseline to mean 24 cells/µL at month 3 and remained low throughout the study following treatment with belimumab. However, CD19+CD27+ cells increased in number at month 6, from a mean 17 cells/µL to 23 cells/µL, and then decreased between months 6 and 12 to 9 cells/µL.

The expression of BAFFR as a percentage of B cells remained unchanged throughout the study, but an increase in BAFFR MFI was seen from baseline to month 3, followed by a decrease at month 12 of treatment with belimumab. The number of CD27+ cells and mean BAFFR MFI showed a similar increase followed by a decrease during the course of the study, according to the researchers.

“The intensity of BAFFR expression on CD27+ B cells may explain the pharmacodynamic of belimumab in SLE,” the researchers wrote. “Since belimumab acts slowly in SLE, the results observed support the hypothesis of a therapeutic effect of belimumab also on CD27+ B cells.” – by Shirley Pulawski

Reference:

Quartuccio L, et al. Paper #THU0402. Presented at: European League Against Rheumatism Annual European Congress of Rheumatology; June 10-13, 2015; Rome.

Disclosure: The researchers report no relevant financial disclosures.