Treatment with Belimumab resulted in a sustained improvement of systemic lupus erythematosus ( SLE or lupus ) disease activity in 46% of patients at week 52.

Historically, it has been difficult to adequately measure the therapeutic responses to drug intervention in SLE patients, due to the diverse presentations of the disease itself.
A novel combined responder index which takes into account three commonly used measures of disease progression, SELENA SLEDAI ( SS ), Physician Global Assessment ( PGA ) and presence of BILAG-classified flares ( new 1A or 2B ), was utilised by the research team to analyse the effect of the BLyS inhibitor Belimumab on the progression of SLE disease activity.

Lead author Ellen Ginzler, of SUNY-Downstate Medical Center, New York, US, commented:

“ While the results demonstrated that treatment with Belimumab resulted in a sustained improvement in SLE symptoms in patients with serologically active disease, we also confirmed that combining multiple disease activity measures is a successful method of assessing overall disease activity, and appears to be associated with the presence of biomarkers and quality of life improvements in responders.”

Patients enrolled in this 52 week randomised, double-blind, placebo-controlled study received Belimumab in doses of 1mg/kg, 4mg/kg and 10mg/kg or placebo plus SLE standard therapy.
Overall, about 70% of subjects were taking Prednisone and/or anti-malarials such as Plaquenil ( used in SLE treatment regimes ); 50% of these subjects were also taking an immunosuppressive drug ( e.g., Methotrexate, Azathioprine, Mycophenolate, Leflunomide ).

The 449 patients entering the study were evaluated according to the disease activity measurement scores SS and Disease Activity Index, PGA, BILAG, SF-36 and biomarkers including B-cell subsets and autoantibodies. 71.5% of the initial 449 patients entered the study with baseline serological activity. An evidence-based combined endpoint was developed that incorporates a response parameter and controls against worsening in other organ systems.

A combined response, consisting of an improvement in SS score of 4 points or more, with no new BILAG 1A or 2B flares, and no worsening in PGA ( < 0.3 point increase ), was observed in serologically-active patients at week 52 ( 46% Belimumab versus 29% placebo, p=0.006 ) and improved further to 56% for the Belimumab-treated population at week 76.

Responders had a greater reduction in activated B-cells ( 36% responders versus 20% non-responders, p less than or equal to 0.05 ). A greater reduction in anti-dsDNA, was also found in responders ( 53% responders versus 38% non-responders, p less than or equal to 0.05 ).
Responders additionally reported a greater improvement in SF-36 Physical Component Summary score ( PCS; increase = 4.1, MCID = 2.5 ) at week 52 than non-responders (increase =1.0, p less than or equal to 0.001).

Belimumab ( LymphoStat-B ) is a human monoclonal antibody that inhibits the biological activity of the B-lymphocyte stimulator ( BlyS ).
BLyS is a naturally occurring soluble protein required for the development of B-lymphocytes into mature plasma B cells which produce antibodies.
In systemic lupus erythematosus, elevated levels of BLyS are believed to contribute to the production of autoantibodies involved in damage to the body’s own healthy tissues, a key marker of SLE disease activity.
B-cell antagonists or inhibitors such as Belimumab are believed to reduce autoantibody levels and help control SLE autoimmune disease activity.

Source: European League Against Rheumatism ( EULAR ), 2007

XagenaMedicine2007


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