Jul. 20, 2010

Belimumab Reduces Lupus Disease Activity After 76 Weeks

Belimumab, a BLyS-Specific Inhibitor, reduces disease activity and severe flares in seropositive SLE patients: BLISS-76 Study
van Vollenhoven RF, Zamani O, Wallace DJ, Tegzova D, Merrill JT, Chatham W, Schwarting A, Hiepe F, Doria A, Sanchez-Guerrero J, Jeka S, Dyczek A, Furie RA, Petri M, D’Cruz D, Fojtik Z, Pineda L, Zhong ZJ, Hough D, Freimuth W, and Cervera R, BLISS 76 Study Group. (2010). 
European League Against Rheumatism Congress Abstracts OP0068.

What is the topic?
Benlysta™ (belimumab) is a treatment that has recently been studied for use in lupus. This treatment is actually an antibody, just like an antibody that might be made by the normal immune system in response to an infection. When antibodies bind to a person’s own proteins, they are called “autoantibodies” and these special kinds of antibodies may be responsible for some of the inflammation seen in lupus. It is interesting to consider the possibility that an autoantibody could also be put to use, under certain circumstances, to inhibit lupus.    

Belimumab is an antibody that binds to a protein of the immune system called B-lymphocyte stimulator (BLyS). BLyS helps one of the immune cells (white blood cells called “B cells”) to survive and trigger inflammation. By inhibiting BLyS, belimumab might help to inhibit inflammation. It is almost as though the same kind of event that contributes to lupus (an antibody binding to a human protein and leading to inflammation) can be put to strategic use to try to prevent lupus (an antibody binding to a certain human protein that usually triggers inflammation, thereby inhibiting its inflammatory activity).   

What did the researchers hope to learn?
The researchers hoped to learn about the safety and potential effectiveness of belimumab in the treatment of lupus.  

Who was studied?
819 lupus patients were studied in a 76-week long international study. The patients had lupus for an average of 7.5 years and had active lupus symptoms even though most of them were taking steroids and/or at least one other treatment for lupus. 

How was the study conducted?
Patients were randomly assigned to receive either placebo or belimumab at one of two doses (either 1 or 10 milligrams per kilogram of body weight). All patients stayed on their background treatments that they were getting upon entry into the study and were allowed to have increases in these treatments during the study if needed. For this reason, there was no real placebo group. Belimumab plus “standard of care” was compared to “standard of care” alone.   

The main outcome measure was the percentage of patients showing significant improvement at 52 and 76 weeks. Improvement was measured by the SLE Responder Index, which combines a measurement of improvement in overall disease activity with evidence that there was no worsening in any given part of the body.

What did the researchers find?
At 52 weeks, patients taking the highest dose of belimumab (10 mg/kg) showed significant improvement compared to those taking placebo. Also, fatigue decreased significantly in patients taking the lower dose of belimumab (1 mg/kg) as compared to those taking placebo.

At 76 weeks, patients taking 10 mg/kg belimumab plus standard of care showed significant improvement compared to those taking placebo plus standard of care. Of the patients taking steroids, more of them were able to reduce their steroid dose if they were taking 1 mg/kg belimumab than if they were taking placebo. In addition, among patients with anti-double-stranded DNA, their levels were significantly reduced in patients taking either 1 or 10 mg/kg of belimumab as compared to those taking placebo. Moreover, in patients with low levels of C4 complement, there was significant improvement in patients taking either 1 or 10 mg/kg of belimumab as compared to those taking placebo. Fatigue also decreased significantly in patients taking 1 mg/kg belimumab as compared to those taking placebo.   

People receiving belimumab were more likely to have a side effect of severe inflammation at the infusion site than people receiving placebo. Six cancers occurred – one in the placebo group, 3 in the 1 mg/kg belimumab group, and 2 in the 10 mg/kg belimumab group. Overall, serious side effects were comparable among belimumab and placebo groups. 

What were the limitations of the study?
This was a large, international trial designed in line with the requirements of regulatory agencies so the results might be considered more reliable than preliminary results reported in earlier and smaller phase studies. Because patients were allowed adjustments in the standard of care treatments they were taking during much of the study, many people in the “placebo” group had a good response to treatment, narrowing the difference that there could possibly be between the belimumab and placebo groups.  

What do the results mean for you?
These results need to be evaluated along with many other results from Phase II and Phase III studies of belimumab. The FDA will be evaluating the entire record of this treatment in the near future to determine whether there is enough evidence of safety and efficacy for it to be approved for wider use in lupus patients.


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