BENLYSTA inhibits the biological activity of B-lymphocyte stimulator, or BLyS®. BLyS is a naturally occurring protein discovered by HGS which is required for the survival and development of B-lymphocyte cells into mature plasma B cells. Plasma B cells produce antibodies, the body’s first line of defense against infection. In lupus and certain other autoimmune diseases, elevated levels of BLyS are believed to contribute to the production of autoantibodies – antibodies that attack and destroy the body’s own healthy tissues. The results of prospective observational studies show a significant correlation of elevated levels of BLyS with SLE disease activity.

BENLYSTA acts by: (1) specifically recognizing and binding to BLyS, (2) inhibiting BLyS’s stimulation of B-cell development, and (3) restoring the potential for autoantibody-producing B cells to undergo the normal process of apoptosis (programmed cell death). Preclinical and clinical studies show that BLyS antagonists such as BENLYSTA can reduce autoantibody levels in SLE. The results of two pivotal Phase 3 trials show that belimumab can reduce SLE disease activity.

BENLYSTA Inhibits the Biological Activity of BLyS

Figure 1. BENLYSTA (belimumab) specifically binds to and inhibits the biological activity of BLyS. Preclinical and clinical results to date show that BENLYSTA can reduce the levels of circulating B cells, including precursor cells to the plasma B cells that produce the body’s normal and abnormal antibodies. This suggests that BENLYSTA may prove useful in the treatment of lupus and certain other autoimmune diseases.

FLARES

• Belimumab significantly delayed time to first SLE disease flare versus placebo (SLE Flare Index/SFI): median = 119 days for 10 mg/kg belimumab, 126 days for 1 mg/kg belimumab, and 84 days for placebo (p=0.0036 and p=0.0026 for 10 mg/kg and 1 mg/kg belimumab, respectively vs. placebo). 
• The risk of having severe SLE disease flares (SFI) was reduced over 52 weeks by 43% in the 10 mg/kg belimumab treatment group and by 24% in the 1 mg/kg belimumab treatment group vs. placebo (p=0.0055 and p=0.1342 for 10 mg/kg and 1 mg/kg belimumab, respectively). 
• The risk of having 1 BILAG A (severe flare) or more than 1 BILAG B (moderate flare) organ domain score was reduced by 42% in the 10 mg/kg belimumab treatment group and by 13% in the 1 mg/kg treatment group vs. placebo (p=0.0016 and p=0.3722 for 10 mg/kg and 1 mg/kg belimumab, respectively).  

DISEASE ACTIVITY

• A significantly greater percentage of patients receiving belimumab achieved a reduction in SELENA SLEDAI score of at least 4 points by Week 52 (p=0.0024 and p=0.019 for 10 mg/kg and 1 mg/kg belimumab, respectively, vs. placebo), with improvement observed for 10 mg/kg belimumab within 4-8 weeks and reaching statistical significance at Week 16 and Weeks 24-52 (p<0.05 vs. placebo). 
• A significantly greater improvement in Physician’s Global Assessment (PGA) at Week 52 was observed in the belimumab treatment groups, with a mean percentage change from baseline of 45.7% for 10 mg/kg belimumab, 39.3% for 1 mg/kg belimumab, and 27.8% for placebo (p<0.0001 and p=0.004 for 10 mg/kg and 1 mg/kg belimumab, respectively, vs. placebo). The improvement in PGA was observed within 4-8 weeks and was sustained through 52 weeks (p<0.05 for both belimumab treatment groups).

STEROID USE

• In patients who were receiving >7.5 mg per day of prednisone at baseline, a significantly higher percentage of patients in the 1 mg/kg belimumab treatment group vs. the placebo group had their average prednisone dose reduced by at least 25% from baseline to 7.5 mg per day or less during the last 12 weeks of study (p=0.025). A higher percentage of patients in the 10 mg/kg belimumab treatment group vs. the placebo group also had their average prednisone dose reduced by at least 25% from baseline to 7.5 mg per day or less during the last 12 weeks of study, but the difference did not reach a level of statistical significance (p=0.053).
• In patients who were receiving <7.5 mg per day of prednisone at baseline, significantly fewer patients in the 10 mg/kg belimumab treatment group vs. the placebo group increased their prednisone use to >7.5 mg per day during the last 20 weeks of study (p<0.05). Fewer increases in prednisone use also were observed in the 1 mg/kg belimumab treatment group vs. the placebo group during the last 20 weeks of study, but the difference did not reach a level of statistical significance.

FATIGUE AND QUALITY OF LIFE

• Improved fatigue scores were observed in the 10 mg/kg belimumab treatment group vs. the placebo group within 4-8 weeks, and both belimumab treatment groups achieved statistically significant improvement of fatigue by Week 52 (FACIT-Fatigue Scale; p<0.05 for both belimumab groups vs. the placebo group). 
• Improvement in health-related quality of life (HRQOL) as measured by the SF-36 Physical Component Summary (PCS) score at Week 24, a prespecified major secondary endpoint, was not significantly different among treatment groups. HRQOL improvement as measured by the SF-36 PCS score at Week 52 was significantly greater in both belimumab treatment groups vs. the placebo group (p=0.025 for 10 mg/kg and p=0.027 for 1 mg/kg belimumab, respectively).

SAFETY

In BLISS-52, belimumab was generally well tolerated, with rates of overall adverse events, serious adverse events, infections and fatalities comparable between belimumab and placebo treatment groups. Serious infections were reported in 5.9% of patients on placebo and 6.1% of patients on belimumab. The most common adverse events were headache, arthralgia, upper respiratory tract infections, urinary tract infection and influenza, and were also comparable between belimumab and placebo treatment groups. No malignancies were reported.


For the full article, go to HGSI's website HERE. 

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Lupus Celebrity