Effects of Blisibimod on Renal and Inflammation Biomarkers and on Serum Immunoglobulin and Infection Risk in Patients with Lupus: Results from the PEARL-SC and Open-Label Extension Studies

Blisibimod is a subcutaneously administered inhibitor of B-cell activating factor (BAFF) that has been evaluated in patients with systemic lupus erythematosus (SLE) in the phase 2b PEARL-SC trial and in an ensuing open-label extension study (NCT01305746). In 2 presentations at the American College of Rheumatology annual meeting held in San Diego, California from October 25-30, 2013, Furie and colleagues discussed data from these studies.

The first analysis (Abstract 1604) evaluated the effects of blisibimod on renal and on inflammation biomarkers in patients with SLE. In the PEARL-SC study, 547 patients with serologically active SLE (SELENA-SLEDAI >6, seropositive for ANA or anti-dsDNA antibodies) were randomized to receive placebo or blisibimod 100 mg or 200 mg weekly, or 200 mg every 4 weeks for a median of 37 weeks. Of these patients, 382 enrolled in the open-label extension study and received blisibimod 200 mg every 4 weeks.

Compared with baseline, decreases in proteinuria were observed with blisibimod, starting at week 12 in subjects with proteinuria of ≥1 g per 24 hours at baseline and in those with ≥0.5 g per 24 hours at baseline. These changes were maintained through week 52. Compared with the placebo group, patients receiving blisibimod showed a tendency toward greater increases in GFR at week 24. Moreover, compared with baseline measures, patients receiving blisibimod demonstrated mean decreases of up to 35 IU of anti–ds-DNA antibodies and increases in complements C3 0.08 g/L) and C4 (0.02 g/L) during a period of 52 weeks. The safety profile for blisibimod was similar to that of placebo during the PEARL-SC trial and the open-label extension study.

In the second study, Furie and colleagues (Abstract 1742) reported on the effects of blisibimod in PEARL-SC and the open-label extension study on CD19+/CD20+ B-cells, serum immunoglobulin (Ig) and infection risk. In the 382 patients with SLE who were available for these analyses, a 60% decrease was seen in the number of peripheral CD19+/CD20+ B-cells, a 14.1% decrease in serum IgG, and a 34.6% decrease in serum IgM in patients receiving blisibimod compared with 3.9% and 9.3% decreases in patients receiving placebo from week 8 through week 52 (P <.001).

However, there were no differences between treatment groups in the number of patients reporting infections—58.2% in the blisibimod group and 62% in the placebo group. In addition, there were no significant imbalances between the 2 groups in other serious adverse events, except for injection-site reactions (15% for blisibimod and 7% for placebo) and a critically low IgG level (<4g/L) in 1 patient receiving blisibimod. Of note, the incidence of serious infectious adverse events was not related to the mean concentration of IgG or IgM levels throughout the duration of the study.

Both of these studies suggest that blisibimod induces pharmacologic effects on IgG and IgM that are consistent with BAFF-mediated inhibition of B-cells and plasma cells, as well as on the inflammatory biomarkers of SLE and the proteinuria that are associated with lupus nephritis. Blisibimod appears to be well-tolerated and does not appear to increase the risk of infection in patients with SLE, even in those with low levels of IgG and IgM. A phase 3 clinical trial with this agent in patients with SLE is currently enrolling.